Body mass index as a classifier to predict biochemical recurrence after radical prostatectomy in patients with lower prostate-specific antigen levels

PubMed Central

Goto, Keisuke; Nagamatsu, Hirotaka; Teishima, Jun; Kohada, Yuki; Fujii, Shinsuke; Kurimura, Yoshimasa; Mita, Koji; Shigeta, Masanobu; Maruyama, Satoshi; Inoue, Yoji; Nakahara, Mitsuru; Matsubara, Akio

2017-01-01

Prostate cancer, one of the most common malignant tumors among men, is closely associated with obesity and, thus far, several studies have suggested the association between obesity and aggressive pathological characteristics in the United States. However, the effect of obesity on prostate cancer mortality is controversial, and it remains unclear whether obesity contributes to the aggressiveness of prostate cancer in Asian patients. The aim of the present study was to investigate the association between body mass index (BMI) and the clinicopathological characteristics of prostate cancer in 2,003 Japanese patients who underwent radical prostatectomy. There was a significant association between higher BMI and higher Gleason score (GS). The multivariate analysis also revealed that BMI was an independent indicator for GS ≥8 at surgery. Moreover, among patients with lower prostate-specific antigen levels, biochemical recurrence-free survival was significantly worse in those with higher BMI. These results suggest that BMI may be a classifier for predicting adverse pathological findings and biochemical recurrence after radical prostatectomy in Japanese patients. PMID:28515927

The prostate health index PHI predicts oncological outcome and biochemical recurrence after radical prostatectomy - analysis in 437 patients

PubMed Central

Maxeiner, Andreas; Kilic, Ergin; Matalon, Julia; Friedersdorff, Frank; Miller, Kurt; Jung, Klaus; Stephan, Carsten; Busch, Jonas

2017-01-01

The purpose of this study was to investigate the Prostate-Health-Index (PHI) for pathological outcome prediction following radical prostatectomy and also for biochemical recurrence prediction in comparison to established parameters such as Gleason-score, pathological tumor stage, resection status (R0/1) and prostate-specific antigen (PSA). Out of a cohort of 460 cases with preoperative PHI-measurements (World Health Organization calibration: Beckman Coulter Access-2-Immunoassay) between 2001 and 2014, 437 patients with complete follow up data were included. From these 437 patients, 87 (19.9%) developed a biochemical recurrence. Patient characteristics were compared by using chi-square test. Predictors were analyzed by multivariate adjusted logistic and Cox regression. The median follow up for a biochemical recurrence was 65 (range 3-161) months. PHI, PSA, [-2]proPSA, PHI- and PSA-density performed as significant variables (p < 0.05) for cancer aggressiveness: Gleason-score <7 or ≥7 (ISUP grade 1 or ≥2) . Concerning pathological tumor stage discrimination and prediction, variables as PHI, PSA, %fPSA, [-2]proPSA, PHI- and PSA-density significantly discriminated between stages

The prostate health index PHI predicts oncological outcome and biochemical recurrence after radical prostatectomy - analysis in 437 patients.

PubMed

Maxeiner, Andreas; Kilic, Ergin; Matalon, Julia; Friedersdorff, Frank; Miller, Kurt; Jung, Klaus; Stephan, Carsten; Busch, Jonas

2017-10-03

The purpose of this study was to investigate the Prostate-Health-Index (PHI) for pathological outcome prediction following radical prostatectomy and also for biochemical recurrence prediction in comparison to established parameters such as Gleason-score, pathological tumor stage, resection status (R0/1) and prostate-specific antigen (PSA). Out of a cohort of 460 cases with preoperative PHI-measurements (World Health Organization calibration: Beckman Coulter Access-2-Immunoassay) between 2001 and 2014, 437 patients with complete follow up data were included. From these 437 patients, 87 (19.9%) developed a biochemical recurrence. Patient characteristics were compared by using chi-square test. Predictors were analyzed by multivariate adjusted logistic and Cox regression. The median follow up for a biochemical recurrence was 65 (range 3-161) months. PHI, PSA, [-2]proPSA, PHI- and PSA-density performed as significant variables (p < 0.05) for cancer aggressiveness: Gleason-score <7 or ≥7 (ISUP grade 1 or ≥2) . Concerning pathological tumor stage discrimination and prediction, variables as PHI, PSA, %fPSA, [-2]proPSA, PHI- and PSA-density significantly discriminated between stages

Pathological and 3 Tesla Volumetric Magnetic Resonance Imaging Predictors of Biochemical Recurrence after Robotic Assisted Radical Prostatectomy: Correlation with Whole Mount Histopathology.

PubMed

Tan, Nelly; Shen, Luyao; Khoshnoodi, Pooria; Alcalá, Héctor E; Yu, Weixia; Hsu, William; Reiter, Robert E; Lu, David Y; Raman, Steven S

2018-05-01

We sought to identify the clinical and magnetic resonance imaging variables predictive of biochemical recurrence after robotic assisted radical prostatectomy in patients who underwent multiparametric 3 Tesla prostate magnetic resonance imaging. We performed an institutional review board approved, HIPAA (Health Insurance Portability and Accountability Act) compliant, single arm observational study of 3 Tesla multiparametric magnetic resonance imaging prior to robotic assisted radical prostatectomy from December 2009 to March 2016. Clinical, magnetic resonance imaging and pathological information, and clinical outcomes were compiled. Biochemical recurrence was defined as prostate specific antigen 0.2 ng/cc or greater. Univariate and multivariate regression analysis was performed. Biochemical recurrence had developed in 62 of the 255 men (24.3%) included in the study at a median followup of 23.5 months. Compared to the subcohort without biochemical recurrence the subcohort with biochemical recurrence had a greater proportion of patients with a high grade biopsy Gleason score, higher preoperative prostate specific antigen (7.4 vs 5.6 ng/ml), intermediate and high D'Amico classifications, larger tumor volume on magnetic resonance imaging (0.66 vs 0.30 ml), higher PI-RADS® (Prostate Imaging-Reporting and Data System) version 2 category lesions, a greater proportion of intermediate and high grade radical prostatectomy Gleason score lesions, higher pathological T3 stage (all p <0.01) and a higher positive surgical margin rate (19.3% vs 7.8%, p = 0.016). On multivariable analysis only tumor volume on magnetic resonance imaging (adjusted OR 1.57, p = 0.016), pathological T stage (adjusted OR 2.26, p = 0.02), positive surgical margin (adjusted OR 5.0, p = 0.004) and radical prostatectomy Gleason score (adjusted OR 2.29, p = 0.004) predicted biochemical recurrence. In this cohort tumor volume on magnetic resonance imaging and pathological variables, including Gleason score, staging and positive surgical margins, significantly predicted biochemical recurrence. This suggests an important new imaging biomarker. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Combination therapy for biochemically recurrent prostate cancer tested in new trial | Center for Cancer Research

Cancer.gov

Prostate-specific antigen (PSA) is an enzyme released by the prostate gland and is found in abnormally high concentrations in the blood of men with prostate cancer. “Biochemical recurrence” is when PSA levels continue to rise after initial treatment for prostate cancer, such as surgery or radiation. Marijo Bilusic, M.D., of the Genitourinary Malignancies Branch is leading the

Coexpression of aPKCλ/ι and IL-6 in prostate cancer tissue correlates with biochemical recurrence.

PubMed

Ishiguro, Hitoshi; Akimoto, Kazunori; Nagashima, Yoji; Kagawa, Eriko; Sasaki, Takeshi; Sano, Jin-yu; Takagawa, Ryo; Fujinami, Kiyoshi; Sasaki, Kazunori; Aoki, Ichiro; Ohno, Shigeo; Kubota, Yoshinobu; Uemura, Hiroji

2011-08-01

Atypical protein kinase C λ/ι (aPKCλ/ι) and interleukin-6 (IL-6) have been implicated in prostate cancer progression, the mechanisms of which have been demonstrated both in vitro and in vivo. However, the clinical significance of the correlation between the expressions of these factors remains to be clarified. In the present study, we report a significant correlation between aPKCλ/ι and IL-6 proteins in prostate cancer tissue by immunohistochemical staining. We evaluated the association of both proteins by analyzing clinicopathological parameters using chi-square test, Kaplan-Meier with log-rank test, and a Cox proportional hazard regression model in univariate and multivariate analyses. The results again showed that the expression of aPKCλ/ι and IL-6 correlates in prostate cancer tissue (P < 0.001). Atypical protein kinase C λ/ι was also found to correlate with the Gleason score (P < 0.001) and with biochemical recurrence after prostatectomy (P = 0.02). Furthermore, aPKCλ/ι correlated with biochemical recurrence in a Kaplan-Meier and log-rank test (P = 0.01) and Cox analysis (P = 0.02 in the univariate analysis, P = 0.02 in the multivariate analysis). The coexpression of aPKCλ/ι and IL-6 also correlated with biochemical recurrence by Kaplan-Meier and log-rank test (P = 0.005) and Cox analysis (P = 0.01 in the univariate analysis, P = 0.03 in the multivariate analysis). These results indicate a strong correlation between aPKCλ/ι and IL-6 in prostate tumors, and that the aPKCλ/ι-IL-6 axis is a reliable prognostic factor for the biochemical recurrence of this cancer. © 2011 Japanese Cancer Association.

Computer extracted texture features on T2w MRI to predict biochemical recurrence following radiation therapy for prostate cancer

NASA Astrophysics Data System (ADS)

Ginsburg, Shoshana B.; Rusu, Mirabela; Kurhanewicz, John; Madabhushi, Anant

2014-03-01

In this study we explore the ability of a novel machine learning approach, in conjunction with computer-extracted features describing prostate cancer morphology on pre-treatment MRI, to predict whether a patient will develop biochemical recurrence within ten years of radiation therapy. Biochemical recurrence, which is characterized by a rise in serum prostate-specific antigen (PSA) of at least 2 ng/mL above the nadir PSA, is associated with increased risk of metastasis and prostate cancer-related mortality. Currently, risk of biochemical recurrence is predicted by the Kattan nomogram, which incorporates several clinical factors to predict the probability of recurrence-free survival following radiation therapy (but has limited prediction accuracy). Semantic attributes on T2w MRI, such as the presence of extracapsular extension and seminal vesicle invasion and surrogate measure- ments of tumor size, have also been shown to be predictive of biochemical recurrence risk. While the correlation between biochemical recurrence and factors like tumor stage, Gleason grade, and extracapsular spread are well- documented, it is less clear how to predict biochemical recurrence in the absence of extracapsular spread and for small tumors fully contained in the capsule. Computer{extracted texture features, which quantitatively de- scribe tumor micro-architecture and morphology on MRI, have been shown to provide clues about a tumor's aggressiveness. However, while computer{extracted features have been employed for predicting cancer presence and grade, they have not been evaluated in the context of predicting risk of biochemical recurrence. This work seeks to evaluate the role of computer-extracted texture features in predicting risk of biochemical recurrence on a cohort of sixteen patients who underwent pre{treatment 1.5 Tesla (T) T2w MRI. We extract a combination of first-order statistical, gradient, co-occurrence, and Gabor wavelet features from T2w MRI. To identify which of these T2w MRI texture features are potential independent prognostic markers of PSA failure, we implement a partial least squares (PLS) method to embed the data in a low{dimensional space and then use the variable importance in projections (VIP) method to quantify the contributions of individual features to classification on the PLS embedding. In spite of the poor resolution of the 1.5 T MRI data, we are able to identify three Gabor wavelet features that, in conjunction with a logistic regression classifier, yield an area under the receiver operating characteristic curve of 0.83 for predicting the probability of biochemical recurrence following radiation therapy. In comparison to both the Kattan nomogram and semantic MRI attributes, the ability of these three computer-extracted features to predict biochemical recurrence risk is demonstrated.

Salvage HDR Brachytherapy for Recurrent Prostate Cancer After Previous Definitive Radiation Therapy: 5-Year Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Chien Peter; Weinberg, Vivian; Shinohara, Katsuto

Purpose: Evaluate efficacy and toxicity of salvage high-dose-rate brachytherapy (HDRB) for locally recurrent prostate cancer after definitive radiation therapy (RT). Methods and Materials: We retrospectively analyzed 52 consecutively accrued patients undergoing salvage HDRB between 1998 and 2009 for locally recurrent prostate cancer after previous definitive RT. After pathologic confirmation of locally recurrent disease, patients received 36 Gy in 6 fractions. Twenty-four patients received neoadjuvant hormonal therapy before salvage, and no patients received adjuvant hormonal therapy. Determination of biochemical failure after salvage HDRB was based on the Phoenix definition. Overall survival (OS) and bF distributions were calculated using the Kaplan-Meier method.more » Univariate analyses were performed to identify predictors of biochemical control. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities, based on Common Terminology Criteria for Adverse Events (version 4), were documented. Results: Median follow-up after salvage HDRB was 59.6 months. The 5-year OS estimate was 92% (95% confidence interval [CI]: 80%-97%) with median survival not yet reached. Five-year biochemical control after salvage was 51% (95% CI: 34%-66%). Median PSA nadir postsalvage was 0.1 (range: 0-7.2) reached at a median of 10.2 months after completing HDRB. As for complications, acute and late grade 3 GU toxicities were observed in only 2% and 2%, respectively. No grade 2 or higher acute GI events and 4% grade 2 GI late events were observed. On univariate analysis, disease-free interval after initial definitive RT (P=.07), percent of positive cores at the time of diagnosis (P=.08), interval from first recurrence to salvage HDRB (P=.09), and pre-HDRB prostate-specific antigen (P=.07) were each of borderline significance in predicting biochemical control after salvage HDRB. Conclusions: Prostate HDRB is an effective salvage modality with relatively few long-term toxicities. We provide potential predictors of biochemical control for prostate salvage HDRB.« less

CD147 expression predicts biochemical recurrence after prostatectomy independent of histologic and pathologic features.

PubMed

Bauman, Tyler M; Ewald, Jonathan A; Huang, Wei; Ricke, William A

2015-07-25

CD147 is an MMP-inducing protein often implicated in cancer progression. The purpose of this study was to investigate the expression of CD147 in prostate cancer (PCa) progression and the prognostic ability of CD147 in predicting biochemical recurrence after prostatectomy. Plasma membrane-localized CD147 protein expression was quantified in patient samples using immunohistochemistry and multispectral imaging, and expression was compared to clinico-pathological features (pathologic stage, Gleason score, tumor volume, preoperative PSA, lymph node status, surgical margins, biochemical recurrence status). CD147 specificity and expression were confirmed with immunoblotting of prostate cell lines, and CD147 mRNA expression was evaluated in public expression microarray datasets of patient prostate tumors. Expression of CD147 protein was significantly decreased in localized tumors (pT2; p = 0.02) and aggressive PCa (≥pT3; p = 0.004), and metastases (p = 0.001) compared to benign prostatic tissue. Decreased CD147 was associated with advanced pathologic stage (p = 0.009) and high Gleason score (p = 0.02), and low CD147 expression predicted biochemical recurrence (HR 0.55; 95 % CI 0.31-0.97; p = 0.04) independent of clinico-pathologic features. Immunoblot bands were detected at 44 kDa and 66 kDa, representing non-glycosylated and glycosylated forms of CD147 protein, and CD147 expression was lower in tumorigenic T10 cells than non-tumorigenic BPH-1 cells (p = 0.02). Decreased CD147 mRNA expression was associated with increased Gleason score and pathologic stage in patient tumors but is not associated with recurrence status. Membrane-associated CD147 expression is significantly decreased in PCa compared to non-malignant prostate tissue and is associated with tumor progression, and low CD147 expression predicts biochemical recurrence after prostatectomy independent of pathologic stage, Gleason score, lymph node status, surgical margins, and tumor volume in multivariable analysis.

Factors predicting biochemical recurrence after radical prostatectomy among patients with clinical T3 prostate cancer.

PubMed

Otsuka, Masafumi; Kamasako, Tomohiko; Uemura, Toshihiro; Takeshita, Nobushige; Shinozaki, Tetsuo; Kobayashi, Masayuki; Komaru, Atsushi; Fukasawa, Satoshi

2018-06-19

The effectiveness of cancer control is unclear after radical prostatectomy for patients with clinical T3 prostate cancer. We retrospectively reviewed 1409 patients who underwent radical prostatectomy between April 2007 and December 2014, including 210 patients with cT3 prostate cancer. Nine patients who received neoadjuvant hormonal therapy and three patients who were lost to follow-up were excluded from the analysis. Clinical staging was performed by an experienced radiologist using preoperative magnetic resonance imaging findings. We analyzed the predictors of biochemical recurrence using Cox proportional hazard analyses. A total of 113 patients (57%) underwent radical retropubic prostatectomy and 85 patients (43%) underwent robot-assisted radical prostatectomy. The median follow-up period was 36 months. Downstaging occurred for 60 patients (30%), positive surgical margins were identified in 117 patients (59%), and biochemical recurrence was observed for 89 patients (45%). In the multivariate analyses, the independent preoperative predictors of biochemical recurrence were ≥50% proportion of positive biopsy cores [hazard ratio (HR): 2.858, P < 0.0001] and a biopsy Gleason score of ≥8 (HR: 1.800, P = 0.0093). The independent post-operative predictors of biochemical recurrence were positive surgical margins (HR: 2.490, P = 0.0018) and seminal vesicle invasion (HR: 2.750, P < 0.0001). Among patients with cT3 prostate cancer, the percentage of positive biopsy cores and the biopsy Gleason score should be considered to select treatment. Compared with radical retropubic prostatectomy, robot-assisted radical prostatectomy may be a feasible treatment option in this setting.

Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology.

PubMed

Walker, Steven M; Knight, Laura A; McCavigan, Andrena M; Logan, Gemma E; Berge, Viktor; Sherif, Amir; Pandha, Hardev; Warren, Anne Y; Davidson, Catherine; Uprichard, Adam; Blayney, Jaine K; Price, Bethanie; Jellema, Gera L; Steele, Christopher J; Svindland, Aud; McDade, Simon S; Eden, Christopher G; Foster, Chris; Mills, Ian G; Neal, David E; Mason, Malcolm D; Kay, Elaine W; Waugh, David J; Harkin, D Paul; Watson, R William; Clarke, Noel W; Kennedy, Richard D

2017-10-01

Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy. To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy. Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 months. Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis. A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13-2.33]; p=0.0092) and metastatic recurrence (multivariable HR=3.20 [1.76-5.80]; p=0.0001). A combined model with Cancer of the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an increased risk of biochemical and metastatic recurrence superior to either model alone (HR=2.67 [1.90-3.75]; p<0.0001 and HR=7.53 [4.13-13.73]; p<0.0001, respectively). The retrospective nature of the study is acknowledged as a potential limitation. The metastatic assay may identify a molecular subgroup of primary prostate cancers with metastatic potential. The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in this higher-risk population. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

[Significance of PSMA imaging in prostate cancer].

PubMed

Gasch, C; Düwel, C; Kopka, K; Kratochwil, C; Vinsensia, M; Eiber, M; Maurer, T; Haberkorn, U; Hadaschik, B; Giesel, F L

2017-01-01

Prostate cancer (PCa) is one of the most common malignancies of men in developed countries. To improve clinical diagnostics of PCa, 68 Ga-PSMA-11 was recently introduced as a new PET tracer. 68 Ga-PSMA-11 is able to specifically bind to the prostate-specific membrane antigen (PSMA), which is upregulated on the surface of prostate cancer cells in most patients. To analyse the current significance of 68 Ga-PSMA-11 PET imaging in prostate cancer in relation to staging of men with initial diagnosis, biochemical recurrence and metastatic disease. Retrospective analysis of current literature (PubMed search) regarding 68 Ga-PSMA-11 PET diagnostics in primary staging, in biochemical recurrence and in metastasized disease. Compared to conventional imaging, 68 Ga-PSMA-11 PET/CT reaches a higher sensitivity with an excellent specificity in the clinical diagnosis of primary staging as well as staging for recurrence and advanced, metastasized disease. In biochemical recurrence, 68 Ga-PSMA-11 PET/CT shows significantly higher detection rates in comparison to choline PET/CT, especially in patients with low PSA values. In the clinical diagnosis of recurrent disease, therapy concepts were changed in more than a quarter of the patients due to the use of 68 Ga-PSMA-11 PET/CT. The significance of staging with 68 Ga-PSMA-11 PET/CT in advanced metastasized patients remains uncertain. Due to the excellent results of 68 Ga-PSMA-11 PET imaging, even in patients with slightly elevated PSA levels, it will continue to play an important role in clinical diagnostics of prostate cancer and, thus, its clinical utilization will become more widely spread.

Patterns of Recurrence After Low-Dose-Rate Prostate Brachytherapy: A Population-Based Study of 2223 Consecutive Low- and Intermediate-Risk Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lo, Andrea C.; Morris, W. James, E-mail: JMorris@bccancer.bc.ca; Pickles, Tom

Objectives: This study examined patterns of recurrence after low–dose-rate prostate brachytherapy (LDR-PB), estimated local recurrence rate and compared that rate to the estimated local recurrence rate after radical prostatectomy (RP). Methods and Materials: A prospective database was maintained with clinical, dosimetric, and outcome data for all LDR-PB implantation procedures performed at our institution. From 1998 to 2008, 2223 patients with prostate cancer received LDR-PB without supplemental external beam radiation therapy. Patients who developed Phoenix-defined biochemical failure were reviewed for sites of relapse and investigations completed. Results: At a median follow-up of 5 years, 108 of 2223 patients (4.8%) developed biochemical relapse.more » In 1 additional patient, local relapse was found on transurethral prostate resection, but his prostate-specific antigen concentration was well short of triggering Phoenix-defined failure. Of the 109 patients with disease relapse, 18 of 2223 (0.8%) had a proven local recurrence, and 30 of 2223 (1.3%) had a proven distant recurrence. The remaining 61 of 2223 patients (2.7%) had unidentified sites of recurrence; of these, 57 patients (93%) had digital rectal examinations (DREs), 18 (30%) had post-treatment biopsies, 45 (74%) had bone scans, and 34 (56%) had computed tomography imaging of the abdomen and pelvis. If every biochemical failure were local, the local recurrence rate would be as high as 4.9%; however, by excluding those with proven distant failure and those with both a negative DRE and biopsy, we estimate that the local recurrence rate is 2.7% or less. Conclusions: In the context of limitations of the study design, our population-based analysis indicates that the local recurrence rate after LDR-PB is as low or lower than that after RP in our jurisdiction.« less

Improved prediction of biochemical recurrence after radical prostatectomy by genetic polymorphisms.

PubMed

Morote, Juan; Del Amo, Jokin; Borque, Angel; Ars, Elisabet; Hernández, Carlos; Herranz, Felipe; Arruza, Antonio; Llarena, Roberto; Planas, Jacques; Viso, María J; Palou, Joan; Raventós, Carles X; Tejedor, Diego; Artieda, Marta; Simón, Laureano; Martínez, Antonio; Rioja, Luis A

2010-08-01

Single nucleotide polymorphisms are inherited genetic variations that can predispose or protect individuals against clinical events. We hypothesized that single nucleotide polymorphism profiling may improve the prediction of biochemical recurrence after radical prostatectomy. We performed a retrospective, multi-institutional study of 703 patients treated with radical prostatectomy for clinically localized prostate cancer who had at least 5 years of followup after surgery. All patients were genotyped for 83 prostate cancer related single nucleotide polymorphisms using a low density oligonucleotide microarray. Baseline clinicopathological variables and single nucleotide polymorphisms were analyzed to predict biochemical recurrence within 5 years using stepwise logistic regression. Discrimination was measured by ROC curve AUC, specificity, sensitivity, predictive values, net reclassification improvement and integrated discrimination index. The overall biochemical recurrence rate was 35%. The model with the best fit combined 8 covariates, including the 5 clinicopathological variables prostate specific antigen, Gleason score, pathological stage, lymph node involvement and margin status, and 3 single nucleotide polymorphisms at the KLK2, SULT1A1 and TLR4 genes. Model predictive power was defined by 80% positive predictive value, 74% negative predictive value and an AUC of 0.78. The model based on clinicopathological variables plus single nucleotide polymorphisms showed significant improvement over the model without single nucleotide polymorphisms, as indicated by 23.3% net reclassification improvement (p = 0.003), integrated discrimination index (p <0.001) and likelihood ratio test (p <0.001). Internal validation proved model robustness (bootstrap corrected AUC 0.78, range 0.74 to 0.82). The calibration plot showed close agreement between biochemical recurrence observed and predicted probabilities. Predicting biochemical recurrence after radical prostatectomy based on clinicopathological data can be significantly improved by including patient genetic information. Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

68Ga Bombesin PET/MRI in Patients with Biochemically Recurrent Prostate Cancer and Noncontributory Conventional Imaging

DTIC Science & Technology

2017-10-01

REPORT DATE: October 2017 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702...AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 11. SPONSOR...prostate cancer (PCa). Methods : We enrolled 15 men with biochemically recurrent PCa from May to Sep 2017, 63-79 year-old (mean±standard deviation (SD

Pretreatment prostate-specific antigen velocity is associated with freedom from biochemical recurrence of prostate cancer after low-dose-rate prostate brachytherapy alone.

PubMed

Rossi, Peter J; Urbanic, James; Clark, Peter E; McCullough, David L; Lee, W Robert

2008-01-01

This report examines the relationship between pretreatment prostate-specific antigen (PSA) velocity (PSAV) and freedom from biochemical recurrence (FFBR) in men with prostate cancer treated with low-dose-rate prostate brachytherapy (LDRPB). This is a report of 51 men treated with LDRPB between 1997 and 1999. two or more evaluable PSA values >3 months apart and <18 months before treatment. PSAV is calculated using a linear regression equation. All patients had biopsy confirmed, clinically localized prostate cancer. All men were treated with (125)I LDRPB. The prescription dose was 144Gy. Biochemical failure is determined from PSA values over time using the ASTRO Consensus Definition. FFBR is estimated using Kaplan-Meier method. Pretreatment variables analyzed include percentage positive biopsy cores, D(90), risk group, and PSAV. All p values are two-sided. The median followup is 60 months. The median pretreatment PSA is 6.5, 75% of men were Stage T1c, and 88% had Gleason score > or =6; 10% developed evidence of biochemical recurrence at a median of 13 months (range, 6-36). The 6-year estimate of FFBR is 90% for the entire cohort. On univariate analysis, pretreatment PSAV and risk group are associated with FFBR. The 6-year estimate of FFBR in patients with a PSAV <2 ng/mL/yr is 100% vs. 80% (95% confidence interval: 64-96%) when the pretreatment PSAV is > or =2 ng/mL/yr before LDRPB (p = 0.017). Pretreatment PSAV is a predictor of FFBR after LDRPB in this population of men with prostate cancer. Men with a pretreatment PSAV > or =2 ng/mL/yr may warrant more aggressive treatment.

Residual Prostate Cancer in Patients Treated With Endocrine Therapy With or Without Radical Radiotherapy: A Side Study of the SPCG-7 Randomized Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Solberg, Arne, E-mail: arne.solberg@stolav.n; Haugen, Olav A.; Department of Pathology and Medical Genetics, St. Olav's Hospital, Trondheim University Hospital, Trondheim

2011-05-01

Purpose: The Scandinavian Prostate Cancer Group-7 randomized trial demonstrated a survival benefit of combined endocrine therapy and external-beam radiotherapy over endocrine therapy alone in patients with high-risk prostate cancer. In a subset of the study population, the incidence and clinical implications of residual prostate cancer in posttreatment prostate biopsy specimens was evaluated. Methods and Materials: Biopsy specimens were obtained from 120 of 875 men in the Scandinavian Prostate Cancer Group-7 study. Results: Biopsies were performed at median of 45 months follow-up. In 63 patients receiving endocrine treatment only and 57 patients receiving combined treatment, residual cancer was found in 66%more » (n = 41) and 22% (n = 12), respectively (p < 0.0001). The vast majority of residual tumors were poorly differentiated (Gleason score {>=}8). Endocrine therapy alone was predictive of residual prostate cancer: odds ratio 7.49 (3.18-17.7), p < 0.0001. In patients with positive vs. negative biopsy the incidences of clinical events were as follows: biochemical recurrence 74% vs. 27% (p < 0.0001), local progression 26% vs. 4.7% (p = 0.002), distant recurrence 17% vs. 9.4% (p = 0.27), clinical recurrence 36% vs. 13% (p = 0.006), cancer-specific death 19% vs. 9.7% (p = 0.025). In multivariable analysis, biochemical recurrence was significantly associated with residual cancer: hazard ratio 2.69 (1.45-4.99), p = 0.002, and endocrine therapy alone hazard ratio 3.45 (1.80-6.62), p < 0.0001. Conclusions: Radiotherapy combined with hormones improved local tumor control in comparison with endocrine therapy alone. Residual prostate cancer was significantly associated with serum prostate-specific antigen recurrence, local tumor progression, clinical recurrence, and cancer-specific death in univariable analysis. Residual cancer was predictive of prostate-specific antigen recurrence in multivariable analysis.« less

External validation of the CAPRA-S score to predict biochemical recurrence, metastasis and mortality after radical prostatectomy in a European cohort.

PubMed

Tilki, Derya; Mandel, Philipp; Schlomm, Thorsten; Chun, Felix K-H; Tennstedt, Pierre; Pehrke, Dirk; Haese, Alexander; Huland, Hartwig; Graefen, Markus; Salomon, Georg

2015-06-01

The CAPRA-S score predicts prostate cancer recurrence based on pathological information from radical prostatectomy. To our knowledge CAPRA-S has never been externally validated in a European cohort. We independently validated CAPRA-S in a single institution European database. The study cohort comprised 14,532 patients treated with radical prostatectomy between January 1992 and August 2012. Prediction of biochemical recurrence, metastasis and cancer specific mortality by CAPRA-S was assessed by Kaplan-Meier analysis and the c-index. CAPRA-S performance to predict biochemical recurrence was evaluated by calibration plot and decision curve analysis. Median followup was 50.8 months (IQR 25.0-96.0). Biochemical recurrence developed in 20.3% of men at a median of 21.2 months (IQR 7.7-44.9). When stratifying patients by CAPRA-S risk group, estimated 5-year biochemical recurrence-free survival was 91.4%, 70.4% and 29.3% in the low, intermediate and high risk groups, respectively. The CAPRA-S c-index to predict biochemical recurrence, metastasis and cancer specific mortality was 0.80, 0.85 and 0.88, respectively. Metastasis developed in 417 men and 196 men died of prostate cancer. The CAPRA-S score was accurate when applied in a European study cohort. It predicted biochemical recurrence, metastasis and cancer specific mortality after radical prostatectomy with a c-index of greater than 0.80. The score can be valuable in regard to decision making for adjuvant therapy. Copyright © 2015. Published by Elsevier Inc.

The relationship between early biochemical failure and perineural invasion in pathological T2 prostate cancer.

PubMed

Endrizzi, J; Seay, T

2000-04-01

To evaluate, in patients with pathologically localized prostate cancer, the relationship between early biochemical failure, i.e. an increasing prostate-specific antigen (PSA) level, and perineural invasion (PNI) on final pathology. The records were reviewed of 171 patients with prostate cancer who underwent prostatectomy at one institution between January 1992 and December 1995. Data on the histology, therapy and PSA level were collected and evaluated. Of the 171 patients with pathologically localized (pT2) prostate cancer, 131 were evaluable; 17 (13%) had a detectable PSA level in the first 5 years after surgery and 63 had PNI in the pathological specimen. Of those with PSA recurrence, 14 had PNI, one had no PNI and in two there was no comment on PNI. In comparison, only 10 of the 17 patients with recurrence had a Gleason sum of >/= 7. Perineural invasion seems to be an important predictor of early outcome in patients with organ-confined prostate cancer treated by prostatectomy. In this series it was the most sensitive predictor of biochemical failure. A more detailed pathological evaluation of prostate cancer may allow the clinician to provide closer surveillance and better informed clinical decision-making.

Evolution of the patient characteristics of candidates for radical prostatectomy and the results obtained with the technique.

PubMed

Sanchís-Bonet, A; Arribas-Gómez, I; Sánchez-Rodríguez, C; Sánchez-Chapado, M

2015-03-01

To evaluate the oncological profile and risk of biochemical recurrence of patients with prostate cancer who underwent radical prostatectomy based on the time period in which the patients were operated. To evaluate the differences in prostate-specific antigen (PSA) at diagnosis of patients with or without biochemical recurrence based on these time periods. Observation carried forward study of a cohort of 972 radical prostatectomies performed during 3 time periods (1994-2000, 2001-2006, 2007-2011). The importance of PSA at diagnosis on the time periods and on biochemical recurrence was assessed using a generalized linear model. The independent predictive behavior of biochemical recurrence was analyzed using Cox regression. The median follow-up was 38 (16-76) months. PSA levels at diagnosis were higher in the period 1994-2000 (12.97ng/mL, P<.001). Seventy-two percent of the patients from the period 2007-2011 were diagnosed as clinical stage T1c (P<.001), compared with 55% from the period 1994-2000. The percentage of extracapsular extension in the specimen decreased from 27% to 18% from the period 1994-2000 to the period 2007-2011 (p<.001). The percentage of patients with biochemical recurrence went from 38% to 14% from the first to the third period (P>.001). The difference between PSA levels at diagnosis for the patients with or without biochemical recurrence was independent of the period (P=.84). The period during which surgery was performed was not an independent predictive factor for biochemical recurrence (P=.09). Patients from the 2007-2011 period had less extracapsular disease in the radical prostatectomy. The period was not an independent predictive factor for biochemical recurrence. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Plasma carotenoids and tocopherols in relation to prostate-specific antigen (PSA) levels among men with biochemical recurrence of prostate cancer.

PubMed

Antwi, Samuel O; Steck, Susan E; Zhang, Hongmei; Stumm, Lareissa; Zhang, Jiajia; Hurley, Thomas G; Hebert, James R

2015-10-01

Although men presenting with clinically localized prostate cancer (PrCA) often are treated with radical prostatectomy or radiation therapy with curative intent, about 25-40% develop biochemically recurrent PrCA within 5 years of treatment, which has no known cure. Studies suggest that carotenoid and tocopherol intake may be associated with PrCA risk and progression. We examined plasma carotenoid and tocopherol levels in relation to prostate-specific antigen (PSA) levels among men with PSA-defined biochemical recurrence of PrCA. Data analyzed were from a 6-month diet, physical activity and stress-reduction intervention trial conducted in South Carolina among biochemically recurrent PrCA patients (n=39). Plasma carotenoids and tocopherol levels were measured using high-performance liquid chromatography (HPLC). Linear regression was used to estimate least-square means comparing PSA levels of men with high versus low carotenoid/tocopherol levels, adjusting for covariates. After adjusting for baseline PSA level, plasma cis-lutein/zeaxanthin level at 3 months was related inversely to PSA level at 3 months (P=0.0008), while α-tocopherol (P=0.01), β-cryptoxanthin (P=0.01), and all-trans-lycopene (P=0.004) levels at 3 months were related inversely to PSA levels at 6-months. Percent increase in α-tocopherol and trans-β-carotene levels from baseline to month 3 were associated with lower PSA levels at 3 and 6 months. Percent increase in β-cryptoxanthin, cis-lutein/zeaxanthin and all-trans-lycopene were associated with lower PSA levels at 6 months only. Certain plasma carotenoids and tocopherols were related inversely to PSA levels at various timepoints, suggesting that greater intake of foods containing these micronutrients might be beneficial to men with PSA-defined PrCA recurrence. Copyright © 2015. Published by Elsevier Ltd.

Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer

DTIC Science & Technology

2015-10-01

metastasis and responses to curcumin 19 Goals: This proposal tests the hypothesis that chemokine biomarkers that predict biochemical recurrence of...prostate cancer regulate metastatic progression of the cancer and curcumin can inhibit metastasis of prostate cancer by antagonizing inflammatory signaling

Pretreatment Endorectal Coil Magnetic Resonance Imaging Findings Predict Biochemical Tumor Control in Prostate Cancer Patients Treated With Combination Brachytherapy and External-Beam Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riaz, Nadeem; Afaq, Asim; Akin, Oguz

Purpose: To investigate the utility of endorectal coil magenetic resonance imaging (eMRI) in predicting biochemical relapse in prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy. Methods and Materials: Between 2000 and 2008, 279 men with intermediate- or high-risk prostate cancer underwent eMRI of their prostate before receiving brachytherapy and supplemental intensity-modulated radiotherapy. Endorectal coil MRI was performed before treatment and retrospectively reviewed by two radiologists experienced in genitourinary MRI. Image-based variables, including tumor diameter, location, number of sextants involved, and the presence of extracapsular extension (ECE), were incorporated with other established clinical variables to predict biochemical control outcomes.more » The median follow-up was 49 months (range, 1-13 years). Results: The 5-year biochemical relapse-free survival for the cohort was 92%. Clinical findings predicting recurrence on univariate analysis included Gleason score (hazard ratio [HR] 3.6, p = 0.001), PSA (HR 1.04, p = 0.005), and National Comprehensive Cancer Network risk group (HR 4.1, p = 0.002). Clinical T stage and the use of androgen deprivation therapy were not correlated with biochemical failure. Imaging findings on univariate analysis associated with relapse included ECE on MRI (HR 3.79, p = 0.003), tumor size (HR 2.58, p = 0.04), and T stage (HR 1.71, p = 0.004). On multivariate analysis incorporating both clinical and imaging findings, only ECE on MRI and Gleason score were independent predictors of recurrence. Conclusions: Pretreatment eMRI findings predict for biochemical recurrence in intermediate- and high-risk prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy. Gleason score and the presence of ECE on MRI were the only significant predictors of biochemical relapse in this group of patients.« less

Detection of Local, Regional, and Distant Recurrence in Patients With PSA Relapse After External-Beam Radiotherapy Using {sup 11}C-Choline Positron Emission Tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Breeuwsma, Anthonius J., E-mail: a.j.breeuwsma@uro.umcg.n; Departments of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen; Pruim, Jan

2010-05-01

Purpose: An elevated serum prostate-specific antigen (PSA) level cannot distinguish between local-regional recurrences and the presence of distant metastases after treatment with curative intent for prostate cancer. With the advent of salvage treatment such as cryotherapy, it has become important to localize the site of recurrence (local or distant). In this study, the potential of {sup 11}C-choline positron emission tomography (PET) to identify site of recurrence was investigated in patients with rising PSA after external-beam radiotherapy (EBRT). Methods and Materials: Seventy patients with histologically proven prostate cancer treated with EBRT and showing biochemical recurrence as defined by American Society formore » Therapeutic Radiology and Oncology consensus statement and 10 patients without recurrence underwent a PET scan using 400 MBq {sup 11}C-choline intravenously. Biopsy-proven histology from the site of suspicion, findings with other imaging modalities, clinical follow-up and/or response to adjuvant therapy were used as comparative references. Results: None of the 10 patients without biochemical recurrence had a positive PET scan. Fifty-seven of 70 patients with biochemical recurrence (median PSA 9.1 ng/mL; mean PSA 12.3 ng/mL) showed an abnormal uptake pattern (sensitivity 81%). The site of recurrence was only local in 41 of 57 patients (mean PSA 11.1 ng/mL at scan), locoregionally and/or distant in 16 of 57 patients (mean PSA 17.7 ng/mL). Overall the positive predictive value and negative predictive value for {sup 11}C-choline PET scan were 1.0 and 0.44 respectively. Accuracy was 84%. Conclusions: {sup 11}C-choline PET scan is a sensitive technique to identify the site of recurrence in patients with PSA relapse after EBRT for prostate cancer.« less

Prediction of Prostate Cancer Recurrence Using Quantitative Phase Imaging

NASA Astrophysics Data System (ADS)

Sridharan, Shamira; Macias, Virgilia; Tangella, Krishnarao; Kajdacsy-Balla, André; Popescu, Gabriel

2015-05-01

The risk of biochemical recurrence of prostate cancer among individuals who undergo radical prostatectomy for treatment is around 25%. Current clinical methods often fail at successfully predicting recurrence among patients at intermediate risk for recurrence. We used a label-free method, spatial light interference microscopy, to perform localized measurements of light scattering in prostatectomy tissue microarrays. We show, for the first time to our knowledge, that anisotropy of light scattering in the stroma immediately adjoining cancerous glands can be used to identify patients at higher risk for recurrence. The data show that lower value of anisotropy corresponds to a higher risk for recurrence, meaning that the stroma adjoining the glands of recurrent patients is more fractionated than in non-recurrent patients. Our method outperformed the widely accepted clinical tool CAPRA-S in the cases we interrogated irrespective of Gleason grade, prostate-specific antigen (PSA) levels and pathological tumor-node-metastasis (pTNM) stage. These results suggest that QPI shows promise in assisting pathologists to improve prediction of prostate cancer recurrence.

Impact of 68Ga-PSMA-11 PET on Management in Patients with Biochemically Recurrent Prostate Cancer.

PubMed

Hope, Thomas A; Aggarwal, Rahul; Chee, Bryant; Tao, Dora; Greene, Kirsten L; Cooperberg, Matthew R; Feng, Felix; Chang, Albert; Ryan, Charles J; Small, Eric J; Carroll, Peter R

2017-12-01

The purpose of this prospective study was to estimate the effect of 68 Ga-labeled prostate-specific membrane antigen (PSMA)-11 PET on the intended management of patients with biochemically recurrent prostate cancer. Methods: Pre- and postimaging surveys were filled out by the referring providers for patients with biochemical recurrence who were imaged using 68 Ga-PSMA-11 PET. The inclusion criterion for this study was a prostate-specific antigen (PSA) doubling time of less than 12 mo after initial treatment (NCT02611882). Of the 150 consecutive patients imaged, 126 surveys were completed (84% response rate). The responses were categorized as major change, minor change, no change, or unknown change. Results: There were 103 patients (82%) with disease detected on 68 Ga-PSMA-11 PET. On the basis of the survey results, there were 67 patients (53.2%) with major changes in management and 8 patients (6.4%) with minor changes. The proportion of cases resulting in a change in management did not significantly differ by baseline PSA level. In patients with PSA levels below 0.2 ng/dL, 7 of 12 patients had disease detected on 68 Ga-PSMA-11 PET, 5 of whom had a major change in management. Conclusion: 68 Ga-PSMA-11 PET resulted in a major change in management in 53% of patients with biochemical recurrence. Further studies are warranted to investigate whether PSMA-based management strategies result in improved outcomes for patients. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Prostate-Specific Membrane Antigen-Negative Metastases-A Potential Pitfall in Prostate-Specific Membrane Antigen PET.

PubMed

Noto, Benjamin; Auf der Springe, Katharina; Huss, Sebastian; Allkemper, Thomas; Stegger, Lars

2018-06-01

Ga-PSMA-11 PET/CT was performed in a 74-year-old man because of biochemical recurrence of prostate cancer following radiation therapy of the prostate gland 24 months earlier. Besides focal nuclide accumulation in the prostate gland suggestive of local recurrence, PET scan revealed no further pathologic uptake. However, CT showed multiple pulmonic nodules suggestive of metastases. Thoracotomy and pathologic examination revealed the nodules to be prostate cancer metastasis. Furthermore, immunohistochemical staining with PSMA antibodies demonstrated a virtual lack of PSMA expression. This case demonstrates the possibility of PSMA-negative metastases of prostate cancer an important pitfall that should be known to physicians interpreting PSMA PET.

Pilot Comparison of ⁶⁸Ga-RM2 PET and ⁶⁸Ga-PSMA-11 PET in Patients with Biochemically Recurrent Prostate Cancer.

PubMed

Minamimoto, Ryogo; Hancock, Steven; Schneider, Bernadette; Chin, Frederick T; Jamali, Mehran; Loening, Andreas; Vasanawala, Shreyas; Gambhir, Sanjiv Sam; Iagaru, Andrei

2016-04-01

Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga(HBED-CC)] ((68)Ga-PSMA-11) is a PET tracer that can detect prostate cancer relapses and metastases by binding to the extracellular domain of PSMA. (68)Ga-labeled DOTA-4-amino-1-carboxymethyl-piperidine-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 ((68)Ga-RM2) is a synthetic bombesin receptor antagonist that targets gastrin-releasing peptide receptors. We present pilot data on the biodistribution of these PET tracers in a small cohort of patients with biochemically recurrent prostate cancer. Seven men (mean age ± SD, 74.3 ± 5.9 y) with biochemically recurrent prostate cancer underwent both (68)Ga-PSMA-11 PET/CT and (68)Ga-RM2 PET/MRI scans. SUVmax and SUVmean were recorded for normal tissues and areas of uptake outside the expected physiologic biodistribution. All patients had a rising level of prostate-specific antigen (mean ± SD, 13.5 ± 11.5) and noncontributory results on conventional imaging. (68)Ga-PSMA-11 had the highest physiologic uptake in the salivary glands and small bowel, with hepatobiliary and renal clearance noted, whereas (68)Ga-RM2 had the highest physiologic uptake in the pancreas, with renal clearance noted. Uptake outside the expected physiologic biodistribution did not significantly differ between (68)Ga-PSMA-11 and (68)Ga-RM2; however, (68)Ga-PSMA-11 localized in a lymph node and seminal vesicle in a patient with no abnormal (68)Ga-RM2 uptake. Abdominal periaortic lymph nodes were more easily visualized by(68)Ga-RM2 in two patients because of lack of interference by radioactivity in the small intestine. (68)Ga-PSMA-11 and (68)Ga-RM2 had distinct biodistributions in this small cohort of patients with biochemically recurrent prostate cancer. Additional work is needed to understand the expression of PSMA and gastrin-releasing peptide receptors in different types of prostate cancer. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Prostate cancer outcome and tissue levels of metal ions

USGS Publications Warehouse

Sarafanov, A.G.; Todorov, T.I.; Centeno, J.A.; MacIas, V.; Gao, W.; Liang, W.-M.; Beam, C.; Gray, Marion A.; Kajdacsy-Balla, A.

2011-01-01

BACKGROUNDThere are several studies examining prostate cancer and exposure to cadmium, iron, selenium, and zinc. Less data are available on the possible influence of these metal ions on prostate cancer outcome. This study measured levels of these ions in prostatectomy samples in order to examine possible associations between metal concentrations and disease outcome.METHODSWe obtained formalin fixed paraffin embedded tissue blocks of prostatectomy samples of 40 patients with PSA recurrence, matched 1:1 (for year of surgery, race, age, Gleason grading, and pathology TNM classification) with tissue blocks from 40 patients without recurrence (n = 80). Case–control pairs were compared for the levels of metals in areas adjacent to tumors. Inductively coupled plasma-mass spectrometry (ICP-MS) was used for quantification of Cd, Fe, Zn, and Se.RESULTSPatients with biochemical (PSA) recurrence of disease had 12% lower median iron (95 µg/g vs. 111 µg/g; P = 0.04) and 21% lower zinc (279 µg/g vs. 346 µg/g; P = 0.04) concentrations in the normal-appearing tissue immediately adjacent to cancer areas. Differences in cadmium (0.489 µg/g vs. 0.439 µg/g; 4% higher) and selenium (1.68 µg/g vs. 1.58 µg/g; 5% higher) levels were not statistically significant in recurrence cases, when compared to non-recurrences (P = 0.40 and 0.21, respectively).CONCLUSIONSThere is an association between low zinc and low iron prostate tissue levels and biochemical recurrence in prostate cancer. Whether these novel findings are a cause or effect of more aggressive tumors, or whether low zinc and iron prostatic levels raise implications for therapy, remains to be investigated. 

Factors determining biochemical recurrence in low-risk prostate cancer patients who underwent radical prostatectomy

PubMed Central

Ün, Sıtkı; Türk, Hakan; Koca, Osman; Divrik, Rauf Taner; Zorlu, Ferruh

2015-01-01

Objective: This study was conducted to research the factors determining biochemical recurrence (BCR) in low-risk localized prostate cancer patients who underwent radical prostatectomy (RP). Materials and methods: We retrospectively analyzed the data of 504 patients who had undergone RP between 2003 and 2013 at our clinic. One hundred and fifty-two patients who underwent RP for low-risk prostate cancer were included in the study. Results: The mean follow-up period for patients was 58.7 (21–229) months. The mean age of the patients was 63.7±7.2 years (49–79). The mean prostate specific antigen (PSA) value was 5.25±4.22 ng/mL (3.58–9.45). The BCR rate after the operation was 25% (38/152). In the univariate analysis, recurrence determining factors were shown to include extracapsular involvement (ECI) (p=0.004), capsular invasion (CI) (p=0.001), age (p=0.014), and tumor size (p=0.006). However, only CI was found to be significant in multivariate analysis (p=0.001). Conclusion: Capsular invasion is an independent risk factor in low-risk prostate cancer patients who underwent RP for BCR. PMID:26328203

No Detrimental Effect of a Positive Family History on Long-Term Outcomes Following Radical Prostatectomy.

PubMed

Brath, Johannes M S; Grill, Sonja; Ankerst, Donna P; Thompson, Ian M; Gschwend, Juergen E; Herkommer, Kathleen

2016-02-01

Overall 1 in 5 patients with prostate cancer has a positive family history. In this report we evaluated the association between family history and long-term outcomes following radical prostatectomy. Patients treated with radical prostatectomy were identified from a German registry, and separated into positive first-degree family history vs negative family history (strictly negative, requiring at least 1 male first-degree relative older than 60 years and no prostate cancer in the family). Kaplan-Meier curves and Cox proportional hazards models were used for association analyses with biochemical recurrence-free and prostate cancer specific survival. Median followup for 7,690 men included in the study was 8.4 years. Of the 754 younger patients less than 55 years old 50.9% (384) had a family history compared to 40.4% of the older patients (2,803; p <0.001). The 10-year biochemical recurrence-free (62.5%) and prostate cancer specific survival (96.1%) rates did not differ between patients with vs without a family history, nor between the younger vs older patient groups (all p >0.05). Prostate specific antigen, pathological stage, node stage and Gleason score were the only significant predictors for biochemical recurrence-free survival, while pathological stage, node stage (all p <0.005) and Gleason score (Gleason 7 vs 6 or less-HR 1.711, 95% CI 1.056-2.774, p = 0.03; Gleason 8 or greater vs 6 or less-HR 4.516, 95% CI 2.776-7.347, p <0.0001) were the only predictors for prostate cancer specific survival. A family history of prostate cancer has no bearing on long-term outcomes after radical prostatectomy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[PSMA-PET/CT has to be performed in every patient with biochemical recurrence following radical prostatectomy for early tumor detection].

PubMed

Kotzerke, Jörg; Böhmer, Dirk; Schlomm, Thorsten; Maurer, Thomas; Beer, Ambros J; Schmidberger, Heinz

2018-06-01

The debate refers the known evidence for PSMA-PET/CT in biochemical recurrence of prostate cancer and consider carefully interdisciplinary in which situation which patient needs imaging to choose the adequate therapeutic option. General aspects for the care of cancer patients are taken into consideration. Schattauer GmbH.

Does Choline PET/CT Change the Management of Prostate Cancer Patients With Biochemical Failure?

PubMed

Goldstein, Jeffrey; Even-Sapir, Einat; Ben-Haim, Simona; Saad, Akram; Spieler, Benjamin; Davidson, Tima; Berger, Raanan; Weiss, Ilana; Appel, Sarit; Lawrence, Yaacov R; Symon, Zvi

2017-06-01

The FDA approved C-11 choline PET/computed tomography (CT) for imaging patients with recurrent prostate cancer in 2012. Subsequently, the 2014 NCCN guidelines have introduced labeled choline PET/CT in the imaging algorithm of patients with suspected recurrent disease. However, there is only scarce data on the impact of labeled choline PET/CT findings on disease management. We hypothesized that labeled-choline PET/CT studies showing local or regional recurrence or distant metastases will have a direct role in selection of appropriate patient management and improve radiation planning in patients with disease that can be controlled using this mode of therapy. This retrospective study was approved by the Tel Aviv Sourasky and Sheba Medical Center's Helsinki ethical review committees. Patient characteristics including age, PSA, stage, prior treatments, and pre-PET choline treatment recommendations based on NCCN guidelines were recorded. Patients with biochemical failure and without evidence of recurrence on physical examination or standard imaging were offered the option of additional imaging with labeled choline PET/CT. Treatment recommendations post-PET/CT were compared with pre-PET/CT ones. Pathologic confirmation was obtained before prostate retreatment. A nonparametric χ test was used to compare the initial and final treatment recommendations following choline PET/CT. Between June 2010 and January 2014, 34 labeled-choline PET/CT studies were performed on 33 patients with biochemical failure following radical prostatectomy (RP) (n=6), radiation therapy (RT) (n=6), brachytherapy (n=2), RP+salvage prostate fossa RT (n=14), and RP+salvage prostate fossa/lymph node RT (n=6). Median PSA level before imaging was 2 ng/mL (range, 0.16 to 79). Labeled choline PET/CT showed prostate, prostate fossa, or pelvic lymph node increased uptake in 17 studies, remote metastatic disease in 9 studies, and failed to identify the cause for biochemical failure in 7 scans.PET/CT altered treatment approach in 18 of 33 (55%) patients (P=0.05). Sixteen of 27 patients (59%) treated previously with radiation were retreated with RT and delayed or eliminated androgen deprivation therapy: 1 received salvage brachytherapy, 10 received salvage pelvic lymph node or prostate fossa irradiation, 2 brachytherapy failures received salvage prostate and lymph nodes IMRT, and 3 with solitary bone metastasis were treated with radiosurgery. Eleven of 16 patients retreated responded to salvage therapy with a significant PSA response (<0.2 ng/mL), 2 patients had partial biochemical responses, and 3 patients failed. The median duration of response was 500±447 days. Two of 6 patients with no prior RT were referred for salvage prostatic fossa RT: 1 received dose escalation for disease identified in the prostate fossa and another had inclusion of "hot" pelvic lymph nodes in the treatment volume. These early results suggest that labeled choline PET/CT imaging performed according to current NCCN guidelines may change management and improve care in prostate cancer patients with biochemical failure by identifying patients for referral for salvage radiation therapy, improving radiation planning, and delaying or avoiding use of androgen deprivation therapy.

Efficacy, Predictive Factors, and Prediction Nomograms for 68Ga-labeled Prostate-specific Membrane Antigen-ligand Positron-emission Tomography/Computed Tomography in Early Biochemical Recurrent Prostate Cancer After Radical Prostatectomy.

PubMed

Rauscher, Isabel; Düwel, Charlotte; Haller, Bernhard; Rischpler, Christoph; Heck, Matthias M; Gschwend, Jürgen E; Schwaiger, Markus; Maurer, Tobias; Eiber, Matthias

2018-05-01

Recently, 68 Ga-labeled prostate-specific membrane antigen (PSMA)-ligand positron-emission tomography (PET) imaging has been shown to improve detection rates in recurrent prostate cancer (PC). However, published studies include only small patient numbers at low prostate-specific antigen (PSA) values. For this study, 272 consecutive patients with biochemical recurrence after radical prostatectomy and PSA value between 0.2 and 1ng/ml were included. The 68 Ga-PSMA-ligand PET/computed tomography (CT) was evaluated, and detection rates were determined and correlated to various clinical variables using univariate and multivariable analyses. Subgroups of patients with very low (0.2-0.5ng/ml) and low (>0.5-1.0ng/ml) PSA values were analyzed. In total, lesions indicative of PC recurrence were detected in 55% (74/134) and 74% (102/138) with very low and low PSA values, respectively. Main sites of recurrence were pelvic or retroperitoneal lymph nodes metastases, followed by local recurrence and bone metastases with higher probability in the low versus very low PSA subgroup. Detection rates significantly increased with higher PSA values, primary pT≥3a, primary pN+ disease, grade group ≥4, previous radiation therapy, and concurrent androgen deprivation therapy (ADT) in univariate analysis. In a multivariable logistic regression model, concurrent ADT and PSA values were identified as most relevant predictors of positive 68 Ga-PSMA-ligand PET/CT. Further, prediction nomograms were established, which may help in estimating pretest PSMA-ligand PET positivity in clinical practice. In our study, 68 Ga-labeled prostate-specific membrane antigen (PSMA)-ligand positron-emission tomography (PET)/computed tomography (CT) detected recurrent disease after radical prostatectomy in 55% (74/134) and 74% (102/138) of patients with very low (0.2-0.5ng/ml) and low (>0.5-1.0ng/ml) prostate-specific antigen values, respectively. On the basis of these data, it seems reasonable to perform 68 Ga-PSMA-ligand PET/CT also in patients with early biochemical recurrence, as it can tailor further therapy decisions (eg, local vs systemic treatment). The established prediction nomograms can further assist urologists in discussions on the use of 68 Ga-PSMA-ligand PET/CT with their patients in specific clinical settings. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Long-term outcomes of open radical retropubic prostatectomy for clinically localized prostate cancer in the prostate-specific antigen era.

PubMed

Dorin, Ryan P; Daneshmand, Siamak; Lassoff, Mark A; Cai, Jie; Skinner, Donald G; Lieskovsky, Gary

2012-03-01

To determine long-term oncological outcomes and complication rates for patients with clinically organ confined prostate adenocarcinoma (PCa) treated with open radical retropubic prostatectomy and pelvic lymph node dissection (RRP/PLND) in the prostate-specific antigen (PSA) era. Outcomes data were obtained from a prospectively maintained prostate cancer database. Patients with cT1/cT2 PCa undergoing RRP/PLND without neoadjuvant therapy between July 1988 and June 2008 were included. Kaplan-Meier and Cox proportional regression models were used to evaluate factors influencing biochemical recurrence, clinical recurrence, and overall survival (OS). A total of 2487 patients met inclusion criteria, and median follow-up was 7.2 years (range 1-21 years). Of the patients, 49.7% were low risk, 33.2% intermediate risk, and 16.1% high risk by D'Amico criteria, and 6% were LN+. The 10-year biochemical recurrence-free survival (BCRFS) for low-, intermediate-, and high-risk patients was 92%, 83%, and 76%, respectively (P < .001), and 10 year OS was 91%, 83%, and 74%, respectively (P < .001). BCRFS at 10 years was 76% and 88% for patients with positive and negative margins, respectively (P < .001). Of the 2487 patients, 11% developed BCR, and 3.7% experienced CR, with 9 local recurrences. The overall complication rate was 2.3%, and the cancer specific mortality rate was 2%. D'Amico risk group, margin status, and LN status are significantly correlated with outcomes in patients undergoing RRP/PLND for clinically localized PCa. Local recurrence and death from prostate cancer are rare in patients undergoing open RRP/PLND for clinically organ confined disease in the PSA era. Copyright © 2012 Elsevier Inc. All rights reserved.

Radiotherapy before and after radical prostatectomy for high-risk and locally advanced prostate cancer.

PubMed

Perez, Bradford A; Koontz, Bridget F

2015-05-01

Men with localized high-risk prostate cancer carry significant risk of prostate cancer-specific mortality. The best treatment approach to minimize this risk is unclear. In this review, we evaluate the role of radiation before and after radical prostatectomy. A critical review of the literature was performed regarding the application of external radiation therapy (RT) in combination with prostatectomy for high-risk localized prostate cancer. Up to 70% of men with high-risk localized disease may require adjuvant therapy because of adverse pathologic features or biochemical recurrence in the absence of systemic disease. The utility of adjuvant RT among men with adverse pathologic features are well established at least regarding minimizing biochemical recurrence risk. The optimal timing of salvage radiation is the subject of ongoing studies. Neoadjuvant RT requires further study but is a potentially attractive method because of decreased radiation field sizes and potential radiobiologic benefits of delivering RT before surgery. Salvage prostatectomy is effective at treating local recurrence after radiation but is associated with significant surgical morbidity. Combining local therapies including radical prostatectomy and RT can be a reasonable approach. Care should be taken at the initial presentation of high-risk localized prostate cancer to consider and plan for the likelihood of multimodality care. Copyright © 2015 Elsevier Inc. All rights reserved.

Focal cryotherapy of localized prostate cancer: a systematic review of the literature.

PubMed

Shah, Taimur Tariq; Ahmed, Hashim; Kanthabalan, Abi; Lau, Benjamin; Ghei, Maneesh; Maraj, Barry; Arya, Manit

2014-11-01

Radical/whole gland treatment for prostate cancer has significant side-effects. Therefore focal treatments such as cryotherapy have been used to treat localized lesions whilst aiming to provide adequate cancer control with minimal side-effects. We performed a systematic review of Pubmed/Medline and Cochrane databases' to yield 9 papers for primary focal prostate cryotherapy and 2 papers for focal salvage treatment (radio-recurrent). The results of 1582 primary patients showed biochemical disease-free survival between 71-93% at 9-70 months follow-up. Incontinence rates were 0-3.6% and ED 0-42%. Recto-urethral fistula occurred in only 2 patients. Salvage focal cryotherapy had biochemical disease-free survival of 50-68% at 3 years. ED occurred in 60-71%. Focal cryotherapy appears to be an effective treatment for primary localized prostate cancer and compares favorably to radical/whole gland treatments in medium-term oncological outcomes and side-effects. Although more studies are needed it is also effective for radio-recurrent cancer with a low complications rates.

Dual-phase (18)F-fluorocholine PET/CT to detect locoregional recurrence of prostate cancer: comparison between each time point of imaging and a summation scan.

PubMed

Tong, Aaron Kian Ti; Zhang, Zoe Xiaozhu; Zaheer, Sumbul; Yan, Xuexian Sean

2016-01-01

Prostate carcinoma is a major health problem, and routine imaging shows only modest results in detecting and restaging clinically localized prostate cancer recurrence. Recent studies have shown promise of radiolabeled analogues of choline for positron emission tomography (PET) scans in patients of biochemical recurrence and that sequentially incremental Fluorocholine (FCH) uptake is associated with malignancy, whereas decreasing tracer activity suggests a benign aetiology. However, this pattern of tracer uptake has not been fully validated, and no standardized (18)F-Fluorocholine ((18)F-FCH) scan protocol is in place yet. This study aimed to better define the role of dual-phase (18)F-FCH PET/computed tomography (CT) imaging using retrospective masked reading focusing on detection of locoregional recurrence/metastasis in patients with biochemical failure after definitive local primary treatment. A total of 32 subjects were enrolled during the period 04/2010 to 05/2014 with histologically proven prostate cancer that was treated with curative intent and had biochemical recurrence. Early scans and delayed imaging of the pelvis were graded separately by blinded readers. Final evaluation using the combination of information from dual-phase studies as a "summation scan" was also performed. Maximum standardized uptake value was computed using regions of interest constructed over focal hyperactivity. Calculations were performed using Statistical Product and Service Solutions, Version 20 for Windows. A composite reference consisting of histopathology, correlation with other imaging, or serum prostate specific antigen (PSA) trend with clinical follow-up of at least 6months was used to determine the true disease status of the patient. Early-phase pelvis imaging sensitivity and specificity were calculated to be 73.1% and 90.9%, respectively. Late-phase pelvis imaging sensitivity and specificity were 80.8% and 100%, respectively. Summation scan sensitivity and specificity were 76.9% and 100%, respectively. The odds ratio of having recurrent disease with an uptrend of SUVmax on dual-phase imaging was 33.3. The optimal cutoff value of PSA was 1.85ng/mL with 80% sensitivity and 62.5% specificity. Single late-phase FCH PET/CT imaging is a reliable scan modality which can detect sites of disease at low levels of PSA which still fulfil the criteria of biochemical recurrence. This will allow clinicians to identify sites for potential biopsy or start locoregional treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

microRNA in Prostate Cancer Racial Disparities and Aggressiveness

DTIC Science & Technology

2015-10-01

1 AWARD NUMBER: W81XWH-13-1-0477 TITLE: microRNA in Prostate Cancer Racial Disparities and Aggressiveness PRINCIPAL INVESTIGATOR: Cathryn...microRNA in Prostate Cancer Racial Disparities and Aggressiveness 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-13-1-0477 5c. PROGRAM ELEMENT NUMBER...final analyses. 15. SUBJECT TERMS prostate cancer, microRNA, racial disparities, African American, genetic polymorphisms, biochemical recurrence

Mutational load of the mitochondrial genome predicts pathological features and biochemical recurrence in prostate cancer.

PubMed

Kalsbeek, Anton M F; Chan, Eva F K; Grogan, Judith; Petersen, Desiree C; Jaratlerdsiri, Weerachai; Gupta, Ruta; Lyons, Ruth J; Haynes, Anne-Maree; Horvath, Lisa G; Kench, James G; Stricker, Phillip D; Hayes, Vanessa M

2016-10-05

Prostate cancer management is complicated by extreme disease heterogeneity, which is further limited by availability of prognostic biomarkers. Recognition of prostate cancer as a genetic disease has prompted a focus on the nuclear genome for biomarker discovery, with little attention given to the mitochondrial genome. While it is evident that mitochondrial DNA (mtDNA) mutations are acquired during prostate tumorigenesis, no study has evaluated the prognostic value of mtDNA variation. Here we used next-generation sequencing to interrogate the mitochondrial genomes from prostate tissue biopsies and matched blood of 115 men having undergone a radical prostatectomy for which there was a mean of 107 months clinical follow-up. We identified 74 unique prostate cancer specific somatic mtDNA variants in 50 patients, providing significant expansion to the growing catalog of prostate cancer mtDNA mutations. While no single variant or variant cluster showed recurrence across multiple patients, we observe a significant positive correlation between the total burden of acquired mtDNA variation and elevated Gleason Score at diagnosis and biochemical relapse. We add to accumulating evidence that total acquired genomic burden, rather than specific mtDNA mutations, has diagnostic value. This is the first study to demonstrate the prognostic potential of mtDNA mutational burden in prostate cancer.

Australian validation of the Cancer of the Prostate Risk Assessment Post-Surgical score to predict biochemical recurrence after radical prostatectomy.

PubMed

Beckmann, Kerri; O'Callaghan, Michael; Vincent, Andrew; Roder, David; Millar, Jeremy; Evans, Sue; McNeil, John; Moretti, Kim

2018-03-01

The Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) score is a simple post-operative risk assessment tool predicting disease recurrence after radical prostatectomy, which is easily calculated using available clinical data. To be widely useful, risk tools require multiple external validations. We aimed to validate the CAPRA-S score in an Australian multi-institutional population, including private and public settings and reflecting community practice. The study population were all men on the South Australian Prostate Cancer Clinical Outcomes Collaborative Database with localized prostate cancer diagnosed during 1998-2013, who underwent radical prostatectomy without adjuvant therapy (n = 1664). Predictive performance was assessed via Kaplan-Meier and Cox proportional regression analyses, Harrell's Concordance index, calibration plots and decision curve analysis. Biochemical recurrence occurred in 342 (21%) cases. Five-year recurrence-free probabilities for CAPRA-S scores indicating low (0-2), intermediate (3-5) and high risk were 95, 79 and 46%, respectively. The hazard ratio for CAPRA-S score increments was 1.56 (95% confidence interval 1.49-1.64). The Concordance index for 5-year recurrence-free survival was 0.77. The calibration plot showed good correlation between predicted and observed recurrence-free survival across scores. Limitations include the retrospective nature and small numbers with higher CAPRA-S scores. The CAPRA-S score is an accurate predictor of recurrence after radical prostatectomy in our cohort, supporting its utility in the Australian setting. This simple tool can assist in post-surgical selection of patients who would benefit from adjuvant therapy while avoiding morbidity among those less likely to benefit. © 2017 Royal Australasian College of Surgeons.

Phase 1 Trial of Everolimus and Radiation Therapy for Salvage Treatment of Biochemical Recurrence in Prostate Cancer Patients Following Prostatectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Narayan, Vivek; Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania; Vapiwala, Neha

Purpose: In up to half of patients treated with salvage radiation therapy (SRT) for rising prostate-specific antigen levels, a second biochemical recurrence ultimately develops. Phosphatase and tensin homolog inactivation is implicated in prostate cancer progression, and upregulation of the mammalian target of rapamycin pathway can lead to tumor hypoxia and radioresistance. Everolimus is a mammalian target of rapamycin inhibitor with both antitumor and radiosensitizing effects. Methods and Materials: We performed a phase 1 study using a modified 3 + 3 dose-escalation design to evaluate the safety and tolerability of everolimus in combination with standard SRT for the treatment of biochemical recurrence following prostatectomy. Aftermore » a 2-week run-in period of everolimus daily therapy, patients received prostate bed irradiation with daily cone beam computed tomography localization in 37 fractions of 1.8 Gy each (total dose, 66.6 Gy). Patients were monitored for both acute (≤90 days) and chronic (>90 days) treatment-related toxicities. Results: Eighteen patients received everolimus at dose levels of 5 mg (n=6), 7.5 mg (n=6), or 10 mg (n=6) daily in conjunction with SRT. No dose-limiting toxicities were observed. Common acute treatment-related toxicities included grade 1 or 2 mucositis (55.6%), grade 1 or 2 fatigue (38.9%), grade 1 or 2 rash (61.1%), and grade 1 urinary symptoms (61.1%). A grade 3 acute toxicity occurred in 4 patients (22.2%) (n=1 for rash, anemia, lymphopenia, and neutropenia), and no patients had a chronic toxicity of grade 3 or greater. After a median follow-up time of 17.8 months (range, 1.2-46.0 months), an undetectable prostate-specific antigen nadir was achieved in 9 patients (56.3%) and a second biochemical recurrence developed in 5 patients (31.3%). Conclusions: Everolimus at a dose of ≤10 mg daily appears to be safe and tolerable in combination with fractionated post-prostatectomy radiation therapy.« less

Phase 1 Trial of Everolimus and Radiation Therapy for Salvage Treatment of Biochemical Recurrence in Prostate Cancer Patients Following Prostatectomy.

PubMed

Narayan, Vivek; Vapiwala, Neha; Mick, Rosemarie; Subramanian, Pearl; Christodouleas, John P; Bekelman, Justin E; Deville, Curtiland; Rajendran, Ramji; Haas, Naomi B

2017-02-01

In up to half of patients treated with salvage radiation therapy (SRT) for rising prostate-specific antigen levels, a second biochemical recurrence ultimately develops. Phosphatase and tensin homolog inactivation is implicated in prostate cancer progression, and upregulation of the mammalian target of rapamycin pathway can lead to tumor hypoxia and radioresistance. Everolimus is a mammalian target of rapamycin inhibitor with both antitumor and radiosensitizing effects. We performed a phase 1 study using a modified 3 + 3 dose-escalation design to evaluate the safety and tolerability of everolimus in combination with standard SRT for the treatment of biochemical recurrence following prostatectomy. After a 2-week run-in period of everolimus daily therapy, patients received prostate bed irradiation with daily cone beam computed tomography localization in 37 fractions of 1.8 Gy each (total dose, 66.6 Gy). Patients were monitored for both acute (≤90 days) and chronic (>90 days) treatment-related toxicities. Eighteen patients received everolimus at dose levels of 5 mg (n=6), 7.5 mg (n=6), or 10 mg (n=6) daily in conjunction with SRT. No dose-limiting toxicities were observed. Common acute treatment-related toxicities included grade 1 or 2 mucositis (55.6%), grade 1 or 2 fatigue (38.9%), grade 1 or 2 rash (61.1%), and grade 1 urinary symptoms (61.1%). A grade 3 acute toxicity occurred in 4 patients (22.2%) (n=1 for rash, anemia, lymphopenia, and neutropenia), and no patients had a chronic toxicity of grade 3 or greater. After a median follow-up time of 17.8 months (range, 1.2-46.0 months), an undetectable prostate-specific antigen nadir was achieved in 9 patients (56.3%) and a second biochemical recurrence developed in 5 patients (31.3%). Everolimus at a dose of ≤10 mg daily appears to be safe and tolerable in combination with fractionated post-prostatectomy radiation therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

The definition of biochemical failure in patients treated with definitive radiotherapy.

PubMed

Kattan, M W; Fearn, P A; Leibel, S; Potters, L

2000-12-01

The American Society for Therapeutic Radiology and Oncology (ASTRO) published a definition for biochemical failure following treatment of prostate cancer. Others have noted difficulties with interpreting this definition and recommended modifications to accommodate special recurrence patterns. We have compared various modifications to the original ASTRO definition on our series of 1213 patients treated with transperineal permanent prostate brachytherapy. The ASTRO modifications we considered adjusted for (1) early censoring of nonrecurrent patients with rising prostate-specific antigen levels (PSA), (2) cumulative rather than consecutive rises (without a decrease) as evidence of recurrence, (3) both of the above, and (4) waiting 2 years before data analysis. The Kaplan-Meier method was used to compute the effects on recurrence rate for patients treated with and without neoadjuvant hormones. With the original ASTRO definition, freedom from recurrence in our series of men who did not receive neoadjuvant hormones was 83% at 4 years. All of the modifications considered had statistically insignificant effects on freedom from recurrence rates, varying from 80% to 83% at 4 years. Patients treated with neoadjuvant hormones also showed very little sensitivity to the recurrence definition employed. Early censoring of equivocal patients and counting cumulative rather than consecutive rises in PSA (without a decrease) had little empiric effect on the ASTRO recurrence rates. However, we favor the addition of both these modifications to the ASTRO definition on conceptual grounds for evaluating patients following any modality (radiation or surgery), whereby a trend over multiple PSA values is used to judge failure.

Gleason grade grouping of prostate cancer is of prognostic value in Asian men.

PubMed

Yeong, Joe; Sultana, Rehena; Teo, Jonathan; Huang, Hong Hong; Yuen, John; Tan, Puay Hoon; Khor, Li Yan

2017-09-01

The International Society of Urological Pathology made recommendations for the use of Grade Groups (GG) originally described by Epstein and colleagues over Gleason score (GS) alone in 2014, which was subsequently adopted by the WHO classification in 2016. The majority of studies validating this revision have been in Caucasian populations. We therefore asked whether the new GG system was retrospectively associated with biochemical disease-free survival in a mixed-ethnicity cohort of Asian men. A total of 680 radical prostatectomies (RPs) from 2005 to 2014 were included. GS from initial biopsy and RP were compared and used to allocate cases to GG, defined as: 1 (GS≤6); 2 (GS 3+4=7); 3 (GS 4+3=7); 4 (GS 4+4=8/5+3=8/3+5=8) and 5 (GS 9-10). Biochemical recurrence was defined as two consecutive post-RP prostate-specific antigen (PSA) levels of >0.2 ng/mL after post-RP PSA reaching the nadir of <0.1 ng/mL. Our data showed that Kaplan-Meier analysis revealed significant differences in biochemical recurrence within Gleason GG based on either biopsy or prostatectomy scoring. Multivariate analysis further confirmed that a higher GG was significantly associated with risk of biochemical recurrence. This GG system had a higher prognostic discrimination for both initial biopsy and RP than GS. Our study validates the use of the revised and updated GG system in a mixed-ethnicity population of Asian men. Higher GG was significantly associated with increased risk of biochemical recurrence. We therefore recommend its use to inform clinical management for patients with prostate cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Update on cryotherapy for localized prostate cancer.

PubMed

Ritch, Chad R; Katz, Aaron E

2009-05-01

Stage migration has led to an increased incidence of localized and low-risk prostate cancer. Intermediate-term data are emerging on the efficacy of cryotherapy, but direct comparison to other therapeutic modalities is difficult as the parameters for recurrence are not well defined. Studies using the American Society for Therapeutic Radiation and Oncology and the Phoenix (nadir plus 2) criteria for biochemical recurrence show that primary cryotherapy appears to be comparable for low-risk prostate cancer as other treatment modalities. In addition, health-related quality-of-life measures have improved with the most recent third-generation systems demonstrating low incontinence and urethrorectal fistula rates. Erectile dysfunction is high with whole gland ablation, but focal therapy may reduce these rates while still ablating unilateral cancerous tissue. Prostate cryotherapy for localized prostate cancer is an evolving but viable therapeutic option. Long-term data are still needed to establish a definitive role for cryosurgery in prostate cancer treatment.

Milk and other dairy foods in relation to prostate cancer recurrence: Data from the cancer of the prostate strategic urologic research endeavor (CaPSURE™).

PubMed

Tat, David; Kenfield, Stacey A; Cowan, Janet E; Broering, Jeanette M; Carroll, Peter R; Van Blarigan, Erin L; Chan, June M

2018-01-01

High-fat dairy, particularly whole milk, in healthy men may increase risk of aggressive prostate cancer. However, data are limited regarding dairy after prostate cancer diagnosis. We conducted a prospective study among 1334 men with non-metastatic prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavor. Men answered a food frequency questionnaire in 2004-2005 (median 2 years after diagnosis) and were followed until 2016 for recurrence, defined as: prostate cancer death, bone metastases, biochemical recurrence, or secondary treatment. Multivariate Cox proportional hazards regression was used to calculate hazards ratios (HR) and 95% confidence intervals (CI) for associations between whole and low-fat milk; total, high-fat, and low-fat dairy; and other dairy items and risk of recurrence. During a median follow-up of 8 years, we observed 137 events. Men who consumed >4 servings/week versus 0-3 servings/month of whole milk had an 73% increased risk of recurrence (HR: 1.73; 95%CI: 1.00, 2.98; P-value = 0.04). Body mass index (BMI) modified the association (P-interaction = 0.01). Among men with a BMI ≥27 kg/m 2 , >4 servings/week versus 0-3 servings/month of whole milk was associated with a 3-fold higher risk of recurrence (HR: 2.96; 95%CI: 1.58, 5.54; P-value < 0.001). No association was seen in men with BMI <27 kg/m 2 . Low-fat milk and other dairy foods were not associated with recurrence. In conclusion, whole milk consumption after prostate cancer diagnosis was associated with increased risk of recurrence, particularly among very overweight or obese men. Men with prostate cancer who choose to drink milk should select non-fat or low-fat options. © 2017 Wiley Periodicals, Inc.

99mTechnetium-based Prostate-specific Membrane Antigen-radioguided Surgery in Recurrent Prostate Cancer.

PubMed

Maurer, Tobias; Robu, Stephanie; Schottelius, Margret; Schwamborn, Kristina; Rauscher, Isabel; van den Berg, Nynke S; van Leeuwen, Fijs W B; Haller, Bernhard; Horn, Thomas; Heck, Matthias M; Gschwend, Jürgen E; Schwaiger, Markus; Wester, Hans-Jürgen; Eiber, Matthias

2018-04-03

Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) can visualize metastatic lesions in recurrent prostate cancer (PC). However, reliable identification of small and/or atypically localized lesions during salvage surgery procedures is challenging. To describe the technique, feasibility, and short-term outcomes of 99m Technetium ( 99m Tc)-based PSMA-radioguided surgery ( 99m Tc-PSMA-RGS) for removal of recurrent PC lesions. Thirty-one consecutive patients with evidence of recurrent PC on 68 Ga-PSMA N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl] ethylenediamine-N,N'-diacetic acid ( 68 Ga-PSMA-11) PET after radical prostatectomy undergoing 99m Tc-PSMA-RGS were retrospectively analyzed. Salvage surgery with intraoperative radioguidance using a gamma probe was performed after intravenous application of 99m Tc-PSMA investigation and surgery (mean activity 571 MBq, mean time to surgery 19.7h). Radioactive rating (positive vs negative) of resected tissue was compared with the findings of postoperative histopathological analysis. Best prostate-specific antigen (PSA) response without additional treatment was determined after 8-16 wk postoperatively. Biochemical recurrence- and treatment-free survival was evaluated. In total, 132 tissue specimens were removed, of which 58 showed metastatic involvement on histological analysis. On a specimen basis, radioactive rating yielded a sensitivity of 83.6% (confidence interval [CI]: 70.9-91.5%), a specificity of 100%, and an accuracy of 93.0% (CI: 85.5-96.7%). With 99m Tc-PSMA-RGS, all lesions visualized on preoperative 68 Ga-PSMA-11 PET could be removed. Moreover, 99m Tc-PSMA-RGS detected additional metastases as small as 3mm in two patients. Thirteen patients suffered from complications related to surgery (Clavien-Dindo grade 1: 12 patients; grade 3a: one patient). A PSA reduction below 0.2 ng/ml was observed in 20 patients. Thirteen patients remained biochemical recurrence free after a median follow-up of 13.8 (range: 4.6-18.3) mo. Twenty patients continued to be treatment free after a median follow-up of 12.2 (range: 5.5-18.3) mo. As a new technique for surgical guidance, 99m Tc-PSMA-RGS is feasible, and has been proved to be of high value for successful intraoperative detection and removal of metastatic lesions in PC patients scheduled for salvage surgery. Its long-term impact on outcome has to be evaluated. In this report, we evaluated a novel technique to identify metastatic lesions intraoperatively in patients with recurrent prostate cancer to facilitate surgical removal. After intravenous injection of radioactive molecules that specifically bind to prostate cancer cells that show increased expression of the prostate-specific membrane antigen, we were able to detect and remove these metastatic lesions during surgery. Following salvage surgery, 41.9% of patients remained biochemical recurrence free (median follow-up of 13.8 mo) and 64.5% continued to be treatment free (median follow-up of 12.2 mo). Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

[PET/CT and biochemical recurrence of prostate adenocarcinoma: Added value of 68Ga-PSMA-11 when 18F-fluorocholine is non-contributive].

PubMed

Gauthé, M; Belissant, O; Girard, A; Zhang Yin, J; Ohnona, J; Cottereau, A-S; Nataf, V; Balogova, S; Pontvert, D; Lebret, T; Guillonneau, B; Cussenot, O; Talbot, J-N

Since April 201, we have introduced PET/CT using a ligand of prostate-specific membrane antigen labeled with gallium-68 (PSMA-11). We aimed to evaluate its positivity rate and impact in patients presenting biochemical recurrence of prostate cancer whose 18 F-fluorocholine (FCH) PET/CT was non-contributive. Patients were prospectively included between April and December 2016. PET/CT was performed 60min after injection of 2MBq/kg of body mass of 68 Ga-PSMA-11. Three anatomical areas were considered: prostatic lodge, pelvic lymph nodes and distant locations. The impact of PSMA-11 PET/CT was assessed by comparing changes in therapeutic strategy decided during multidisciplinary meeting. Thirty-three patients were included. The mean PSA serum level measured on the month of the PSMA-11 PET/CT was 2,8ng/mL. Twenty-five (76%) PSMA-11 PET/CT were positive, 7 (21%) negative and 1 (3%) equivocal. Of 11 patients whose FCH PET/CT showed equivocal foci, PSMA-11 PET/CT confirmed those foci in 5 cases. Follow-up was available for 18 patients (55%). PSMA-11 PET/CT results led to a change in management in 12 patients (67%). 68 Ga-PSMA-11 PET/CT is useful in detecting recurrence of prostate cancer, by identifying residual disease which was not detected on other imaging modalities and by changing management of 2 patients out of 3. 5. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Optimal MRI sequences for 68Ga-PSMA-11 PET/MRI in evaluation of biochemically recurrent prostate cancer.

PubMed

Lake, Spencer T; Greene, Kirsten L; Westphalen, Antonio C; Behr, Spencer C; Zagoria, Ronald; Small, Eric J; Carroll, Peter R; Hope, Thomas A

2017-09-19

PET/MRI can be used for the detection of disease in biochemical recurrence (BCR) patients imaged with 68 Ga-PSMA-11 PET. This study was designed to determine the optimal MRI sequences to localize positive findings on 68 Ga-PSMA-11 PET of patients with BCR after definitive therapy. Fifty-five consecutive prostate cancer patients with BCR imaged with 68 Ga-PSMA-11 3.0T PET/MRI were retrospectively analyzed. Mean PSA was 7.9 ± 12.9 ng/ml, and mean PSA doubling time was 7.1 ± 6.6 months. Detection rates of anatomic correlates for prostate-specific membrane antigen (PSMA)-positive foci were evaluated on small field of view (FOV) T2, T1 post-contrast, and diffusion-weighted images. For prostate bed recurrences, the detection rate of dynamic contrast-enhanced (DCE) imaging for PSMA-positive foci was evaluated. Finally, the detection sensitivity for PSMA-avid foci on 3- and 8-min PET acquisitions was compared. PSMA-positive foci were detected in 89.1% (49/55) of patients evaluated. Small FOV T2 performed best for lymph nodes and detected correlates for all PSMA-avid lymph nodes. DCE imaging performed the best for suspected prostate bed recurrence, detecting correlates for 87.5% (14/16) of PSMA-positive prostate bed foci. The 8-min PET acquisition performed better than the 3-min acquisition for lymph nodes smaller than 1 cm, detecting 100% (57/57) of lymph nodes less than 1 cm, compared to 78.9% (45/57) for the 3-min acquisition. PSMA PET/MRI performed well for the detection of sites of suspected recurrent disease in patients with BCR. Of the MRI sequences obtained for localization, small FOV T2 images detected the greatest proportion of PSMA-positive abdominopelvic lymph nodes and DCE imaging detected the greatest proportion of PSMA-positive prostate bed foci. The 8-min PET acquisition was superior to the 3 min acquisition for detection of small lymph nodes.

MRI-guided Dose-escalated Salvage Radiotherapy for Bulky Bladder Neck Recurrence of Prostate Cancer

PubMed Central

Tyran, Marguerite; Steinberg, Michael L.; Holden, Stuart B; Cao, Minsong

2018-01-01

Nearly 30% of patients treated with radical prostatectomy for prostate cancer ultimately develop biochemical recurrences, and nearly a quarter of men with nonpalpable biochemical recurrences have gross local recurrences identified with magnetic resonance imaging (MRI). The only curative intervention for patients with recurrent disease after radical prostatectomy is salvage radiotherapy – this is particularly true for patients with gross local recurrences. Furthermore, even in patients with an incurable metastatic disease, a local recurrence can be the source of significant morbidity and should be addressed. Delivering a sufficient dose of radiation in the postoperative setting to control gross disease while minimizing toxicity poses a significant technical challenge. Because of the inherent uncertainty in the verification of gross disease positioning with standard onboard imaging technologies, large margins must be used. Larger margins, in turn, will lead to larger volumes of tissue receiving high doses of radiation, potentially increasing long-term toxicity. Herein, we present the case of a patient with a bulky gross recurrence (>40 cm3) at the bladder neck and synchronous metastatic disease who was referred for salvage radiotherapy after a multidisciplinary consensus recommendation to pursue local therapy for mitigating urinary morbidity from the bulky tumor. The case illustrates the utilization of MRI-guided radiotherapy to allow significant margin reduction, thereby facilitating the delivery of an escalated dose of radiotherapy to a bulky recurrence. PMID:29805929

High-Intensity Focused Ultrasound (HIFU) for the Treatment of Localized Prostate Cancer using Sonablate-500

NASA Astrophysics Data System (ADS)

Uchida, Toyoaki; Ohkusa, Hiroshi; Yamashita, Hideyuki; Nagata, Yoshihiro

2005-03-01

We evaluated 181 patients with localized prostate cancer treated with high-intensity focused ultrasound (HIFU) for biochemical disease-free rate, safety, morbidity and predictors of biochemical outcome. A total of 181 patients underwent HIFU with the Sonablate-500 and with at least 12 months of follow-up. Biochemical failure was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The biochemical disease-free rates at 1, 3 and 5 years in all patients were 84%, 80% and 78%, respectively. The biochemical disease-free rates at 3 years for patients with pretreatment PSA less than 10 ng/ml, 10.01 to 20.0 ng/ml and more than 20.0 ng/ml were 94%, 75% and 35%, respectively (p<0.0001). According to multivariate analysis preoperative PSA (p<0.0001) was a significant independent predictor of time to biochemical recurrence. HIFU therapy appears to be a safe and efficacious minimally invasive therapy for patients with localized prostate cancer, especially those with a pretreatment PSA level less than 20 ng/ml.

High-Intensity Focused Ultrasound (HIFU) Using Sonablate-500 for the Treatment of Localized Prostate Cancer: 6-year experience

NASA Astrophysics Data System (ADS)

Uchida, Toyoaki; Shoji, Sunao; Nagata, Yoshihiro

2006-05-01

We evaluated 281 patients of localized prostate cancer treated with high-intensity focused ultrasound (HIFU) for biochemical disease-free rate, safety, morbidity and predictors of biochemical outcome. A total of 281 patients underwent HIFU with the use of Sonablate-500 and with at least 12 months of follow-up. Biochemical failure was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The biochemical disease-free rates at 1, 3 and 5 years in all patients were 78%, 74% and 72%, respectively. The biochemical disease-free rates at 5 years for patients with pretreatment PSA less than 10 ng/ml, 10.01 to 20.0 ng/ml and more than 20.0 ng/ml were 88%, 70% and 17%, respectively (p<0.0001). According to multivariate analysis preoperative PSA (p<0.0001) was significant independent predictors of time to biochemical recurrence. HIFU therapy appears to be a safe and efficacious minimally invasive therapy for patients with localized prostate cancer, especially those with a pretreatment PSA level less than 20 ng/ml.

Concurrent nuclear ERG and MYC protein overexpression defines a subset of locally advanced prostate cancer: Potential opportunities for synergistic targeted therapeutics.

PubMed

Udager, Aaron M; DeMarzo, Angelo M; Shi, Yang; Hicks, Jessica L; Cao, Xuhong; Siddiqui, Javed; Jiang, Hui; Chinnaiyan, Arul M; Mehra, Rohit

2016-06-01

Recurrent ERG gene fusions, the most common genetic alterations in prostate cancer, drive overexpression of the nuclear transcription factor ERG, and are early clonal events in prostate cancer progression. The nuclear transcription factor MYC is also frequently overexpressed in prostate cancer and may play a role in tumor initiation and/or progression. The relationship between nuclear ERG and MYC protein overexpression in prostate cancer, as well as the clinicopathologic characteristics and prognosis of ERG-positive/MYC high tumors, is not well understood. Immunohistochemistry (IHC) for ERG and MYC was performed on formalin-fixed, paraffin-embedded tissue from prostate cancer tissue microarrays (TMAs), and nuclear staining was scored semi-quantitatively (IHC product score range = 0-300). Correlation between nuclear ERG and MYC protein expression and association with clinicopathologic parameters and biochemical recurrence after radical prostatectomy was assessed. 29.1% of all tumor nodules showed concurrent nuclear ERG and MYC protein overexpression (i.e., ERG-positive/MYC high), including 35.0% of secondary nodules. Overall, there was weak positive correlation between ERG and MYC expression across all tumor nodules (rpb  = 0.149, P = 0.045), although this correlation was strongest in secondary nodules (rpb  = 0.520, P = 0.019). In radical prostatectomy specimens, ERG-positive/MYC high tumors were positively associated with the presence of extraprostatic extension (EPE), relative to all other ERG/MYC expression subgroups, however, there was no significant association between concurrent nuclear ERG and MYC protein overexpression and time to biochemical recurrence. Concurrent nuclear ERG and MYC protein overexpression is common in prostate cancer and defines a subset of locally advanced tumors. Recent data indicates that BET bromodomain proteins regulate ERG gene fusion and MYC gene expression in prostate cancer, suggesting possible synergistic targeted therapeutics in ERG-positive/MYC high tumors. Prostate 76:845-853, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Prostate tissue metal levels and prostate cancer recurrence in smokers.

PubMed

Neslund-Dudas, Christine; Kandegedara, Ashoka; Kryvenko, Oleksandr N; Gupta, Nilesh; Rogers, Craig; Rybicki, Benjamin A; Dou, Q Ping; Mitra, Bharati

2014-02-01

Although smoking is not associated with prostate cancer risk overall, smoking is associated with prostate cancer recurrence and mortality. Increased cadmium (Cd) exposure from smoking may play a role in progression of the disease. In this study, inductively coupled plasma mass spectrometry was used to determine Cd, arsenic (As), lead (Pb), and zinc (Zn) levels in formalin-fixed paraffin embedded tumor and tumor-adjacent non-neoplastic tissue of never- and ever-smokers with prostate cancer. In smokers, metal levels were also evaluated with regard to biochemical and distant recurrence of disease. Smokers (N = 25) had significantly higher Cd (median ppb, p = 0.03) and lower Zn (p = 0.002) in non-neoplastic tissue than never-smokers (N = 21). Metal levels were not significantly different in tumor tissue of smokers and non-smokers. Among smokers, Cd level did not differ by recurrence status. However, the ratio of Cd ppb to Pb ppb was significantly higher in both tumor and adjacent tissue of cases with distant recurrence when compared with cases without distant recurrence (tumor tissue Cd/Pb, 6.36 vs. 1.19, p = 0.009, adjacent non-neoplastic tissue Cd/Pb, 6.36 vs. 1.02, p = 0.038). Tissue Zn levels were also higher in smokers with distant recurrence (tumor, p = 0.039 and adjacent non-neoplastic, p = 0.028). These initial findings suggest that prostate tissue metal levels may differ in smokers with and without recurrence. If these findings are confirmed in larger studies, additional work will be needed to determine whether variations in metal levels are drivers of disease progression or are simply passengers of the disease process.

A comparison of radical retropubic with perineal prostatectomy for localized prostate cancer within the Uniformed Services Urology Research Group.

PubMed

Lance, R S; Freidrichs, P A; Kane, C; Powell, C R; Pulos, E; Moul, J W; McLeod, D G; Cornum, R L; Brantley Thrasher J

2001-01-01

To review and compare the outcome of patients undergoing radical retropubic prostatectomy (RRP) or radical perineal prostatectomy (RPP) for clinically localized prostate cancer. From 1988 to 1997, 1382 men who were treated by RRP and 316 by RPP were identified from databases of the Uniformed Services Urology Research Group. The following variables were assessed; age, race, prostate-specific antigen (PSA) level before surgery, clinical stage, biopsy Gleason sum, estimated blood loss (EBL), margin-positive rate, pathological stage, biochemical recurrence rate, short and long-term complication rates, impotence and incontinence rates. To eliminate selection bias, the analysis was concentrated on pairs of patients matched by race, preoperative PSA level, clinical stage and biopsy Gleason sum. In the 190 matched patients there were no significant differences between the RRP and RPP groups in either organ-confined (57% vs 55%), margin-positive (39% vs 43%), or biochemical recurrence rates (12.9% vs 17.6% at a mean follow-up of 47.1 vs 42.9 months), respectively. The mean EBL was 1575 mL in the RRP group and 802 mL in the RPP group (P < 0.001). The only significant difference in complication rates was a higher incidence of rectal injury in the RPP group (4.9%) than in the RRP group (none, P < 0.05). In similar populations of patients, RPP offers equivalent organ-confined, margin-positive and biochemical recurrence rates to RRP, while causing significantly less blood loss.

Pathological and Biochemical Outcomes among African-American and Caucasian Men with Low Risk Prostate Cancer in the SEARCH Database: Implications for Active Surveillance Candidacy.

PubMed

Leapman, Michael S; Freedland, Stephen J; Aronson, William J; Kane, Christopher J; Terris, Martha K; Walker, Kelly; Amling, Christopher L; Carroll, Peter R; Cooperberg, Matthew R

2016-11-01

Racial disparities in the incidence and risk profile of prostate cancer at diagnosis among African-American men are well reported. However, it remains unclear whether African-American race is independently associated with adverse outcomes in men with clinical low risk disease. We retrospectively analyzed the records of 895 men in the SEARCH (Shared Equal Access Regional Cancer Hospital) database in whom clinical low risk prostate cancer was treated with radical prostatectomy. Associations of African-American and Caucasian race with pathological biochemical recurrence outcomes were examined using chi-square, logistic regression, log rank and Cox proportional hazards analyses. We identified 355 African-American and 540 Caucasian men with low risk tumors in the SEARCH cohort who were followed a median of 6.3 years. Following adjustment for relevant covariates African-American race was not significantly associated with pathological upgrading (OR 1.33, p = 0.12), major upgrading (OR 0.58, p = 0.10), up-staging (OR 1.09, p = 0.73) or positive surgical margins (OR 1.04, p = 0.81). Five-year recurrence-free survival rates were 73.4% in African-American men and 78.4% in Caucasian men (log rank p = 0.18). In a Cox proportional hazards analysis model African-American race was not significantly associated with biochemical recurrence (HR 1.11, p = 0.52). In a cohort of patients at clinical low risk who were treated with prostatectomy in an equal access health system with a high representation of African-American men we observed no significant differences in the rates of pathological upgrading, up-staging or biochemical recurrence. These data support continued use of active surveillance in African-American men. Upgrading and up-staging remain concerning possibilities for all men regardless of race. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The Cancer of the Prostate Risk Assessment (CAPRA) score predicts biochemical recurrence in intermediate-risk prostate cancer treated with external beam radiotherapy (EBRT) dose escalation or low-dose rate (LDR) brachytherapy.

PubMed

Krishnan, Vimal; Delouya, Guila; Bahary, Jean-Paul; Larrivée, Sandra; Taussky, Daniel

2014-12-01

To study the prognostic value of the University of California, San Francisco Cancer of the Prostate Risk Assessment (CAPRA) score to predict biochemical failure (bF) after various doses of external beam radiotherapy (EBRT) and/or permanent seed low-dose rate (LDR) prostate brachytherapy (PB). We retrospectively analysed 345 patients with intermediate-risk prostate cancer, with PSA levels of 10-20 ng/mL and/or Gleason 7 including 244 EBRT patients (70.2-79.2 Gy) and 101 patients treated with LDR PB. The minimum follow-up was 3 years. No patient received primary androgen-deprivation therapy. bF was defined according to the Phoenix definition. Cox regression analysis was used to estimate the differences between CAPRA groups. The overall bF rate was 13% (45/345). The CAPRA score, as a continuous variable, was statistically significant in multivariate analysis for predicting bF (hazard ratio [HR] 1.37, 95% confidence interval [CI] 1.10-1.72, P = 0.006). There was a trend for a lower bF rate in patients treated with LDR PB when compared with those treated by EBRT ≤ 74 Gy (HR 0.234, 95% CI 0.05-1.03, P = 0.055) in multivariate analysis. In the subgroup of patients with a CAPRA score of 3-5, CAPRA remained predictive of bF as a continuous variable (HR 1.51, 95% CI 1.01-2.27, P = 0.047) in multivariate analysis. The CAPRA score is useful for predicting biochemical recurrence in patients treated for intermediate-risk prostate cancer with EBRT or LDR PB. It could help in treatment decisions. © 2013 The Authors. BJU International © 2013 BJU International.

Pathological, Oncologic and Functional Outcomes of a Prospective Registry of Salvage High Intensity Focused Ultrasound Ablation for Radiorecurrent Prostate Cancer.

PubMed

Siddiqui, Khurram M; Billia, Michele; Arifin, Andrew; Li, Fan; Violette, Philippe; Chin, Joseph L

2017-01-01

In this prospective registry we prospectively assessed the oncologic, functional and safety outcomes of salvage high intensity focused ultrasound for radiorecurrent prostate cancer. A total of 81 men were prospectively recruited and evaluated at regular scheduled study visits to 6 months after high intensity focused ultrasound and thereafter as per standard of care. Transrectal ultrasound guided biopsy was performed at 6 months. The primary end point was absence or histological persistence of disease at 6-month biopsy. Secondary end points included quality of life, biochemical recurrence-free survival, overall survival, cancer specific survival and progression to androgen deprivation therapy. Survival analysis was performed according to the Kaplan-Meier method and multivariate analysis was performed using the log rank (Mantel-Cox) test. Mean ± SD prostate specific antigen before high intensity focused ultrasound was 4.06 ± 2.88 ng/ml. At 6 months 63 men underwent biopsy, of whom 22 (35%) had residual disease. At a mean followup of 53.5 ± 31.6 months median biochemical recurrence-free survival was 63 months. The 5-year overall and cancer specific survival rates were 88% and 94.4%, respectively. Nadir prostate specific antigen less than 0.5 ng/ml was a significant predictor of biochemical recurrence-free survival (p=0.014, 95% CI 1.22-5.87). I-PSS significantly increased (p <0.001) while IIEF-5 scores decreased and the SF-36 score did not change significantly. The rate of rectal fistulization and severe incontinence was 3.7% each. A total of 223 complications were recorded in the 180 days after high intensity focused ultrasound (Clavien-Dindo grade 1-195, grade II-20, grade III-7, grade IVa-1). Salvage high intensity focused ultrasound appears to be a viable treatment option for radiorecurrent prostate cancer, with acceptable morbidity. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

68Ga-PSMA PET/CT in Patients With Biochemical Recurrence of Prostate Cancer: A Prospective, 2-Center Study.

PubMed

Zacho, Helle D; Nielsen, Julie B; Dettmann, Katja; Haberkorn, Uwe; Langkilde, Niels C; Jensen, Jørgen B; Petersen, Lars J

2018-06-19

The aim of this study was to prospectively investigate the detection rate of Ga-PSMA PET/CT in biochemical recurrence (BCR) of prostate cancer and its impact on patient management. Patients with BCR after curatively intended treatment of prostate cancer were included. Each patient underwent a Ga-PSMA PET/CT. Changes in patient management based on the results of Ga-PSMA PET/CT were assessed. Seventy patients were included. Sixty-four patients (91%) had radical prostatectomy, of whom 17 patients (24%) received salvage radiation therapy due to first biochemical relapse. Six patients (9%) underwent radiation therapy as the primary treatment. Ga-PSMA PET/CT detected recurrent disease in 37 patients (53%). The detection rate was 22% for prostate-specific antigen (PSA) levels up to 0.5 ng/mL compared with 83% for PSA levels greater than 0.5 ng/mL. Pathological uptake of Ga-PSMA was observed in 4 (16%) of 21, 4 (44%) of 9, 0 of 1, 7 (70%) of 10, and 22 (88%) of 25 patients with PSA levels from 0.2 to 0.3 ng/mL, 0.31 to 0.4 ng/mL, 0.41 to 0.5 ng/mL, 0.51 to 1 ng/mL, and greater than 1 ng/mL, respectively. Prostate-specific antigen was significantly higher in PSMA-positive patients than in PSMA-negative patients. In 15 (22%) of 69 patients, the results caused a definite change in patient management, and in another 15 (22%) of 69 patients, Ga-PSMA PET/CT guided the choice of treatment. Ga-PSMA PET/CT detects lesions in a large proportion of patients with BCR. Detection rates at low PSA levels (<0.5 ng/mL) were notably below the values reported in previous retrospective studies; however, detection rates improved with increasing PSA levels.

11C-Choline PET/CT based Helical Tomotherapy as Treatment Approach for Bone Metastases in Recurrent Prostate Cancer Patients.

PubMed

Incerti, Elena; Gangemi, Vincenzo; Mapelli, Paola; Deantoni, Chiara Lucrezia; Giovacchini, Giampiero; Fallanca, Federico; Fodor, Andrei; Ciarmiello, Andrea; Baldari, Sergio; Gianolli, Luigi; Di Muzio, Nadia; Picchio, Maria

2017-11-10

To evaluate the efficacy of 11C-choline PET/CT (CHO-PET/CT) based helical tomotherapy (HTT) as a therapeutic approach for bone metastases in recurrent prostate cancer (PCa) patients. This retrospective study includes 20 PCa patients (median age: 67; range: 51-80 years) presenting biochemical relapse after primary treatment who underwent CHO-PET/CT based HTT on positive bone metastases from December 2007 to June 2014. The effectiveness of HTT has been assessed with biochemical response at 3/6/12 months, biochemical relapse free survival (bRFS) and overall survival (OS) at 2 years. Toxicity has also been considered and assessed according to Common Terminology Criteria for Adverse Events (CTCAE). All patients presented a relapse at the time of CHO-PET/CT at bone level. In addition 15/20 (75%) also at lymph nodes (LNs) level (total lesions= 54). All patients underwent HTT on bone metastases and 19/20 concomitantly on prostatic bed and LNs. The median follow-up from CHO-PET/CT was 2 years (range: 1-7 years). At 3 months after the beginning of HTT treatment complete or partial biochemical response occurred in 79% of patients, at 6 months in 82% and at 12 months in 63% of patients. bRFS and OS at 2 years were 50% and 55% of patients, respectively. Patients presented mostly grade 1 or 2 toxicity according to CTCAE. The only grade 3 late toxicity has been observed in one patient. CHO-PET/CT based HTT is a suitable therapeutic approach in patients with recurrent PCa presenting bone metastases with a medium-low toxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Salvage cryotherapy for recurrent prostate cancer after radiation therapy: the Columbia experience.

PubMed

de la Taille, A; Hayek, O; Benson, M C; Bagiella, E; Olsson, C A; Fatal, M; Katz, A E

2000-01-01

Cryotherapy of the prostate represents a potential treatment for localized recurrent prostate cancer after radiation therapy. We report our experience and evaluate the predictive factors for prostate-specific antigen (PSA) recurrence. Between October 1994 and April 1999, 43 patients underwent salvage cryoablation. All patients had biopsy-proven recurrent prostate cancer without seminal vesicle invasion, negative bone scans, and negative lymph node dissection. Patients had received 3 months of combined hormonal therapy before cryosurgery. Biochemical recurrence-free survival (bRFS) was defined as a PSA value less than 0.1 ng/mL. Complications included incontinence (9%), obstruction (5%), urethral stricture (5%), rectal pain (26%), urinary infection (9%), scrotal edema (12%), and hematuria (5%). The mean follow-up was 21.9 months (range 1.2 to 54). Twenty-six patients (60%) reached a serum PSA nadir less than 0.1 ng/mL, 16 (37%) had a PSA less than 4 ng/mL, and 1 (3%) had a PSA less than 10 ng/mL. The bRFS rate was 79% at 6 months and 66% at 12 months. The bRFS rate was higher for patients who had an undetectable postcryotherapy PSA than for patients who did not reach a PSA less than 0. 1 ng/mL (73% versus 30%, P = 0.0076). Using multivariate analysis, a PSA nadir greater than 0.1 ng/mL was an independent predictor of PSA recurrence. Current salvage cryotherapy of the prostate can result in undetectable serum PSA levels with low morbidity. Our data support the current safety and efficacy profile. We believe that cryotherapy is a viable option in the treatment of patients who have biopsy-proven local failure after radiation therapy for prostate cancer. Further refinements in technique and equipment may enhance cryosurgical results.

Prostate-specific Membrane Antigen PET: Clinical Utility in Prostate Cancer, Normal Patterns, Pearls, and Pitfalls.

PubMed

Hofman, Michael S; Hicks, Rodney J; Maurer, Tobias; Eiber, Matthias

2018-01-01

Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is overexpressed in prostate cancer. Radiolabeled small molecules that bind with high affinity to its active extracellular center have emerged as a potential new diagnostic standard of reference for prostate cancer, resulting in images with extraordinary tumor-to-background contrast. Currently, gallium 68 ( 68 Ga)-PSMA-11 (or HBED-PSMA) is the most widely used radiotracer for PSMA positron emission tomography (PET)/computed tomography (CT) or PSMA PET/magnetic resonance (MR) imaging. Evolving evidence demonstrates superior sensitivity and specificity of PSMA PET compared to conventional imaging, with frequent identification of subcentimeter prostate cancer lesions. PSMA PET is effective for imaging disease in the prostate, lymph nodes, soft tissue, and bone in a "one-stop-shop" examination. There is emerging evidence for its clinical value in staging of high-risk primary prostate cancer and localization of disease in biochemical recurrence. The high sensitivity provided by PSMA PET, with frequent identification of small-volume disease, is redefining patterns of disease spread compared with those seen at conventional imaging. In metastatic castration-resistant prostate cancer, PSMA PET is frequently used for theranostic selection (eg, lutetium 177-PSMA radionuclide therapy), but its potential use for therapy monitoring is still under debate. However, evidence on its proper use to improve patient-related outcomes, particularly in the setting of early biochemical recurrence and targeted treatment of oligometastatic disease, is still missing. Despite the term prostate specific, PSMA functions as a folate hydrolase and is expressed in a range of normal tissues and in other benign and malignant processes. Knowledge of its physiologic distribution and other causes of uptake is essential to minimize false-positive imaging findings. © RSNA, 2018.

Salvage radiotherapy in prostate cancer patients. Planning, treatment response and prognosis using (11)C-choline PET/CT.

PubMed

García, J R; Cozar, M; Soler, M; Bassa, P; Riera, E; Ferrer, J

2016-01-01

To assess the prognostic value of the therapeutic response by (11)C-choline PET/CT in prostate cancer patients with biochemical recurrence in which (11)C-choline PET/CT indicated radio-guided radiotherapy. The study included 37 patients initially treated with prostatectomy, who were treated due to biochemical recurrence. (11)C-choline PE/CT detected infra-diaphragmatic lymph-node involvement. All were selected for intensity modulated radiation therapy, escalating the dose according to the PET findings. One year after treatment patients underwent PSA and (11)C-choline PET/CT categorizing response (complete/partial/progression). Clinical/biochemical/image monitoring was performed until appearance of second relapse or 36 months in disease-free patients. (11)C-choline PET/CT could detect lymph nodes in all 37 patients. They were 18 (48.6%) of more than a centimetre in size and 19 (51.3%) with no pathological CT morphology: 9 (24.3%) with positive lymph nodes of around one centimetre and 10 (27.0%) only less than a centimetre in size. The response by (11)C-choline PET/CT was categorised one year after radiotherapy: 16 patients (43.2%) complete response; 15 (40.5%) partial response, and 6 (16.2%) progression. The response was concordant between the PSA result and (11)C-choline PET/CT in 32 patients (86.5%), and discordant in five (13.5%). New recurrence was detected in 12 patients (80%) with partial response, and 5 (31.2%) with complete response. The mean time to recurrence was 9 months after partial response, and 18 months after complete response (significant difference, p<.0001). (11)C-choline PET/CT allows the selection of patients with recurrent prostate cancer candidates for radiotherapy and to plan the technique. The evaluation of therapeutic response by (11)C-choline PET/CT has prognostic significance. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Metabolomic signatures of aggressive prostate cancer.

PubMed

McDunn, Jonathan E; Li, Zhen; Adam, Klaus-Peter; Neri, Bruce P; Wolfert, Robert L; Milburn, Michael V; Lotan, Yair; Wheeler, Thomas M

2013-10-01

Current diagnostic techniques have increased the detection of prostate cancer; however, these tools inadequately stratify patients to minimize mortality. Recent studies have identified a biochemical signature of prostate cancer metastasis, including increased sarcosine abundance. This study examined the association of tissue metabolites with other clinically significant findings. A state of the art metabolomics platform analyzed prostatectomy tissues (331 prostate tumor, 178 cancer-free prostate tissues) from two independent sites. Biochemicals were analyzed by gas chromatography-mass spectrometry and ultrahigh performance liquid chromatography-tandem mass spectrometry. Statistical analyses identified metabolites associated with cancer aggressiveness: Gleason score, extracapsular extension, and seminal vesicle and lymph node involvement. Prostate tumors had significantly altered metabolite profiles compared to cancer-free prostate tissues, including biochemicals associated with cell growth, energetics, stress, and loss of prostate-specific biochemistry. Many metabolites were further associated with clinical findings of aggressive disease. Aggressiveness-associated metabolites stratified prostate tumor tissues with high abundances of compounds associated with normal prostate function (e.g., citrate and polyamines) from more clinically advanced prostate tumors. These aggressive prostate tumors were further subdivided by abundance profiles of metabolites including NAD+ and kynurenine. When added to multiparametric nomograms, metabolites improved prediction of organ confinement (AUROC from 0.53 to 0.62) and 5-year recurrence (AUROC from 0.53 to 0.64). These findings support and extend earlier metabolomic studies in prostate cancer and studies where metabolic enzymes have been associated with carcinogenesis and/or outcome. Furthermore, these data suggest that panels of analytes may be valuable to translate metabolomic findings to clinically useful diagnostic tests. Copyright © 2013 Wiley Periodicals, Inc.

PSA-stratified detection rates for [68Ga]THP-PSMA, a novel probe for rapid kit-based 68Ga-labeling and PET imaging, in patients with biochemical recurrence after primary therapy for prostate cancer.

PubMed

Derlin, Thorsten; Schmuck, Sebastian; Juhl, Cathleen; Zörgiebel, Johanna; Schneefeld, Sophie M; Walte, Almut C A; Hueper, Katja; von Klot, Christoph A; Henkenberens, Christoph; Christiansen, Hans; Thackeray, James T; Ross, Tobias L; Bengel, Frank M

2018-06-01

[ 68 Ga]Tris(hydroxypyridinone)(THP)-PSMA is a novel radiopharmaceutical for one-step kit-based radiolabelling, based on direct chelation of 68 Ga 3+ at low concentration, room temperature and over a wide pH range, using direct elution from a 68 Ge/ 68 Ga-generator. We evaluated the clinical detection rates of [ 68 Ga]THP-PSMA PET/CT in patients with biochemically recurrent prostate cancer after prostatectomy. Consecutive patients (n=99) referred for evaluation of biochemical relapse of prostate cancer by [ 68 Ga]THP-PSMA PET/CT were analyzed retrospectively. Patients underwent a standard whole-body PET/CT (1 h p.i.), followed by delayed (3 h p.i.) imaging of the abdomen. PSA-stratified cohorts of positive PET/CT results, standardized uptake values (SUVs) and target-to-background ratios (TBRs) were analyzed, and compared between standard and delayed imaging. At least one lesion suggestive of recurrent or metastatic prostate cancer was identified on PET images in 52 patients (52.5%). Detection rates of [ 68 Ga]THP-PSMA PET/CT increased with increasing PSA level: 94.1% for a PSA value of ≥10 ng/mL, 77.3% for a PSA value of 2 to <10 ng/mL, 54.5% for a PSA value of 1 to <2 ng/mL, 14.3% for a PSA value of 0.5 to <1 ng/mL, 20.0% for a PSA value of >0.2 to <0.5, and 22.2% for a PSA value of 0.01 to 0.2 ng/mL. [ 68 Ga]THP-PSMA uptake (SUVs) in metastases decreased over time, whereas TBRs improved. Delayed imaging at 3 h p.i. exclusively identified pathologic findings in 2% of [ 68 Ga]THP-PSMA PET/CT scans. Detection rate was higher in patients with a Gleason score ≥8 (P=0.02) and in patients receiving androgen deprivation therapy (P=0.003). In this study, [ 68 Ga]THP-PSMA PET/CT showed suitable detection rates in patients with biochemical recurrence of prostate cancer and PSA levels ≥ 2 ng /mL. Detections rates were lower than in previous studies evaluating other PSMA ligands, though prospective direct radiotracer comparison studies are mandatory particularly in patients with low PSA levels to evaluate the relative performance of different PSMA ligands.

Gleason grade remains an important prognostic predictor in men diagnosed with prostate cancer while on finasteride therapy

PubMed Central

CARVER, BRETT S.; KATTAN, MICHAEL W.; SCARDINO, PETER T.; EASTHAM, JAMES A.

2007-01-01

OBJECTIVE To evaluate men treated with finasteride for lower urinary tract symptoms, who subsequently were diagnosed with prostate cancer and had a radical prostatectomy (RP) at our institution, to determine if finasteride therapy prevented accurate Gleason grade assignment and prediction of biochemical recurrence. PATIENTS AND METHODS Between May 1996 and July 2003, 45 men were identified who had RP and had previously been treated with finasteride for ≥6 months before the diagnosis of prostate cancer. Clinical and pathological information was gathered from a RP database. Serum prostate-specific antigen (PSA) level, duration of finasteride therapy, biopsy Gleason grade, clinical stage, RP Gleason grade and pathological stage were reviewed. Freedom from recurrence was predicted using validated nomograms before and after RP, and compared against actuarial 5-year freedom from recurrence using the Kaplan-Meier method. RESULTS The mean duration of finasteride therapy before diagnosis was 23.6 months, the mean serum PSA (doubled to account for finasteride use) 11.02 ng/mL and mean biopsy Gleason score 6. When comparing the biopsy and RP specimen Gleason score, it was downgraded by 1 point in six men, upgraded by 1 point in eight, and upgraded by 2 points in one. The Gleason score was constant in 30 patients. The nomograms predicted freedom from recurrence in 83% and 85%, respectively; the 5-year actuarial freedom from recurrence was 86%. CONCLUSION Finasteride does not appear to compromise the assignment of Gleason grade for use in prediction tools before or after RP in men undergoing prostate biopsy or RP. The actuarial 5-year freedom from recurrence was similar to that predicted by the validated nomograms. Gleason grade remains an important prognostic predictor in men treated with finasteride and undergoing RP for clinically localized prostate cancer. PMID:15705069

Up regulation of the steroid hormone synthesis regulator HSD3B2 is linked to early PSA recurrence in prostate cancer.

PubMed

Neubauer, Emily; Latif, Morwari; Krause, Jenny; Heumann, Asmus; Armbrust, Moritz; Luehr, Clara; Fraune, Christoph; Hube-Magg, Claudia; Kluth, Martina; Möller-Koop, Christina; Sauter, Guido; Simon, Ronald; Beyer, Burkhard; Pompe, Raisa S; Thederan, Imke; Schlomm, Thorsten; Büscheck, Franziska

2018-05-24

HSD3B2 plays a crucial role in steroid hormone biosynthesis and is thus of particular interest in hormone dependent tumors such as prostate cancer. To clarify the clinical relevance of HSD3B2 expression in prostate cancer, we analyzed HSD3B2 protein expression by immunohistochemistry on our preexisting tissue microarray with 12.247 annotated cancers. Compared with normal tissue cytoplasmic HSD3B2 staining was stronger in prostate cancers. In 9371 interpretable cancers, HSD3B2 expression was found in 95.5% of cancers and was considered weak in 29.9%, moderate in 40.7% and strong in 24.9%. HSD3B2 up regulation was linked to advanced pathological tumor stage (pT), high Gleason grade, elevated preoperative PSA levels (p < 0.0001 each), lymph node metastasis (p = 0.0019), accelerated cell proliferation (p < 0.0001), androgen receptor (AR) expression (p < 0.0001), and early biochemical recurrence (p < 0.0001). HSD3B2 up regulation was only marginally more frequent in ERG positive (98%) than in ERG negative cancers (94%; p < 0.0001) and was strongly linked to deletions of 5q and 6q (p < 0.0001 each). Multivariate analyses showed that the prognostic impact of HSD3B2 expression was independent of established preoperative, but not of postoperative prognostic parameters. In summary, the results of our study demonstrate that HSD3B2 is strongly up regulated in a fraction of prostate cancers that are characterized by increased AR signaling, adverse tumor phenotype and early biochemical recurrence. Copyright © 2018 Elsevier Inc. All rights reserved.

Early dynamic imaging in 68Ga- PSMA-11 PET/CT allows discrimination of urinary bladder activity and prostate cancer lesions.

PubMed

Uprimny, Christian; Kroiss, Alexander Stephan; Decristoforo, Clemens; Fritz, Josef; Warwitz, Boris; Scarpa, Lorenza; Roig, Llanos Geraldo; Kendler, Dorota; von Guggenberg, Elisabeth; Bektic, Jasmin; Horninger, Wolfgang; Virgolini, Irene Johanna

2017-05-01

PET/CT with 68 Ga-labelled prostate-specific membrane antigen (PSMA)-ligands has been proven to establish a promising imaging modality in the work-up of prostate cancer (PC) patients with biochemical relapse. Despite a high overall detection rate, the visualisation of local recurrence may be hampered by high physiologic tracer accumulation in the urinary bladder on whole body imaging, usually starting 60 min after injection. This study sought to verify whether early dynamic 68 Ga-PSMA-11 (HBED-CC)PET/CT can differentiate pathologic PC-related tracer uptake from physiologic tracer accumulation in the urinary bladder. Eighty consecutive PC patients referred to 68 Ga -PSMA-11 PET/CT were included in this retrospective analysis (biochemical relapse: n = 64; primary staging: n = 8; evaluation of therapy response/restaging: n = 8). In addition to whole-body PET/CT acquisition 60 min post injection early dynamic imaging of the pelvis in the first 8 min after tracer injection was performed. SUV max of pathologic lesions was calculated and time-activity curves were generated and compared to those of urinary bladder and areas of physiologic tracer uptake. A total of 55 lesions consistent with malignancy on 60 min whole body imaging exhibited also pathologic 68 Ga-PSMA-11 uptake during early dynamic imaging (prostatic bed/prostate gland: n = 27; lymph nodes: n = 12; bone: n = 16). All pathologic lesions showed tracer uptake within the first 3 min, whereas urinary bladder activity was absent within the first 3 min of dynamic imaging in all patients. Suv max was significantly higher in PC lesions in the first 6 min compared to urinary bladder accumulation (p < 0.001). In the subgroup of PC patients with biochemical relapse the detection rate of local recurrence could be increased from 20.3 to 29.7%. Early dynamic imaging in 68 Ga-PSMA-11 PET/CT reliably enables the differentiation of pathologic tracer uptake in PC lesions from physiologic bladder accumulation. Performance of early dynamic imaging in addition to whole body imaging 60 min after tracer injection might improve the detection rate of local recurrence in PC patients with biochemical relapse referred for 68 Ga-PSMA-11 PET/CT.

MAGI2 is an independent predictor of biochemical recurrence in prostate cancer.

PubMed

David, Stephanie N; Arnold Egloff, Shanna A; Goyal, Rajen; Clark, Peter E; Phillips, Sharon; Gellert, Lan L; Hameed, Omar; Giannico, Giovanna A

2018-06-01

Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 (MAGI2) promotes the activity of phosphatase and tensin homolog (PTEN). Recent studies suggest that dysregulation of this signaling pathway has a role in prostate carcinogenesis. Our study aims to determine the prognostic significance of MAGI2 expression in prostate cancer. Tissue microarrays from 51 radical prostatectomy cases including benign prostatic tissue, high grade prostatic intraepithelial neoplasia (HGPIN), and adenocarcinoma were constructed. Immunohistochemistry with double staining for MAGI2 and p63 was performed and analyzed by image analysis as percent of analyzed area (%AREA). Multivariable logistic regression was used to correlate MAGI2 expression with clinical outcomes. Generalized Estimating Equations (GEE) with linear and logistic regression was used to correlate MAGI2 with intrapatient histology. MAGI2 %AREA was inversely associated with progression from HGPIN to adenocarcinoma of low to high Gleason score (OR, 0.980; slope, -0.02; P = 0.005) and HGPIN to cancer of any Gleason score (OR, 0.969; P = 0.007). After adjusting for grade, stage, and margin status, MAGI2 %AREA was a significant independent predictor of biochemical recurrence (BCR) (OR, 0.936; 95%CI, 0.880-0.996; P = 0.037; bootstrap P = 0.017). The addition of MAGI2 %AREA to these standard clinical parameters improved accuracy of predicting BCR by 2.9% (91.0% vs 88.1%). These results reveal that MAGI2 expression is reduced during prostate cancer progression and that retention of MAGI2 signal reduces odds of BCR. The study results further suggest a possible role of MAGI2 in prostate neoplasia. Decreased MAGI2 expression may help predict prostate cancer aggressiveness and provide new insight for treatment decisions and post-operative surveillance intervals. © 2018 Wiley Periodicals, Inc.

Salvage High-intensity Focused Ultrasound for the Recurrent Prostate Cancer after Radiotherapy

NASA Astrophysics Data System (ADS)

Shoji, S.; Nakano, M.; Omata, T.; Harano, Y.; Nagata, Y.; Usui, Y.; Terachi, T.; Uchida, T.

2010-03-01

To investigate the use of minimally invasive high-intensity focused ultrasound (HIFU) as a salvage therapy in men with localized prostate cancer recurrence following external beam radiotherapy (EBRT), brachytherapy or proton therapy. A review of 20 cases treated using the Sonablate® 500 HIFU device, between August 28, 2002 and September 1, 2009, was carried out. All men had presumed organ-confined, histologically confirmed recurrent prostate adenocarcinoma following radiation therapy. All men with presumed, organ-confined, recurrent disease following EBRT in 8 patients, brachytherapy in 7 patients or proton therapy in 5 patients treated with salvage HIFU were included. The patients were followed for a mean (range) of 16.0 (3-80) months. Biochemical disease-free survival (bDFS) rates in patients with low-intermediate and high risk groups were 86% and 50%, respectively. Side-effects included urethral stricture in 2 of the 16 patients (13%), urinary tract infection or dysuria syndrome in eight (26%), and urinary incontinence in one (6%). Recto-urethral fistula occurred in one patient (6%). Transrectal HIFU is an effective treatment for recurrence after radiotherapy especially in patients with low- and intermediate risk groups.

Promoter methylation of the immune checkpoint receptor PD-1 (PDCD1) is an independent prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy.

PubMed

Goltz, Diane; Gevensleben, Heidrun; Dietrich, Jörn; Ellinger, Jörg; Landsberg, Jennifer; Kristiansen, Glen; Dietrich, Dimo

2016-01-01

Biomarkers that facilitate the prediction of disease recurrence in prostate cancer (PCa) may enable physicians to personalize treatment for individual patients. In the current study, PD-1 ( PDCD1 ) promoter methylation was assessed in a cohort of 498 PCa patients included in The Cancer Genome Atlas (TCGA) and a second cohort of 300 PCa cases treated at the University Hospital of Bonn. In the TCGA cohort, the PD-1 promoter was significantly hypermethylated in carcinomas versus normal prostatic epithelium (55.5% vs. 38.2%, p < 0.001) and PD-1 methylation ( mPD-1 ) inversely correlated with PD-1 mRNA expression in PCa (Spearman's ρ = -0.415, p < 0.001). In both cohorts, mPD-1 significantly correlated with preoperative prostate specific antigen (PSA). In univariate Cox Proportional Hazard analysis, mPD-1 served as a significant prognostic factor for biochemical recurrence (BCR)-free survival (Hazard ratio: HR = 2.35 [1.35-4.10], p = 0.003, n = 410) in the TCGA cohort. In multivariate analysis, mPD-1 was shown to add significant independent prognostic information adjunct to pathologic tumor category (pT) and Gleason grading group (HR = 2.08 [1.16-3.74], p = 0.014, n = 350). PD-1 promoter methylation analyses could thus potentially aid the identification of patients which might benefit from adjuvant treatment after radical prostatectomy. Moreover, our data suggest an intrinsic role of PD-1 in PCa carcinogenesis and disease progression, which needs to be addressed in future studies.

Surgery confounds biology: the predictive value of stage-, grade- and prostate-specific antigen for recurrence after radical prostatectomy as a function of surgeon experience.

PubMed

Vickers, Andrew J; Savage, Caroline J; Bianco, Fernando J; Klein, Eric A; Kattan, Michael W; Secin, Fernando P; Guilloneau, Bertrand D; Scardino, Peter T

2011-04-01

Statistical models predicting cancer recurrence after surgery are based on biologic variables. We have shown previously that prostate cancer recurrence is related to both tumor biology and to surgical technique. Here, we evaluate the association between several biological predictors and biochemical recurrence across varying surgical experience. The study included two separate cohorts: 6,091 patients treated by open radical prostatectomy and an independent replication set of 2,298 patients treated laparoscopically. We calculated the odds ratios for biological predictors of biochemical recurrence-stage, Gleason grade and prostate-specific antigen (PSA)-and also the predictive accuracy (area under the curve, AUC) of a multivariable model, for subgroups of patients defined by the experience of their surgeon. In the open cohort, the odds ratio for Gleason score 8+ and advanced pathologic stage, though not PSA or Gleason score 7, increased dramatically when patients treated by surgeons with lower levels of experience were excluded (Gleason 8+: odds ratios 5.6 overall vs. 13.0 for patients treated by surgeons with 1,000+ prior cases; locally advanced disease: odds ratios of 6.6 vs. 12.2, respectively). The AUC of the multivariable model was 0.750 for patients treated by surgeons with 50 or fewer cases compared to 0.849 for patients treated by surgeons with 500 or more. Although predictiveness was lower overall for the independent replication set cohort, the main findings were replicated. Surgery confounds biology. Although our findings have no direct clinical implications, studies investigating biological variables as predictors of outcome after curative resection of cancer should consider the impact of surgeon-specific factors. Copyright © 2010 UICC.

Phase II Study of Dutasteride for Recurrent Prostate Cancer During Androgen Deprivation Therapy

PubMed Central

Shah, Satyan K.; Trump, Donald L.; Sartor, Oliver; Tan, Wei; Wilding, Gregory E.; Mohler, James L.

2010-01-01

Purpose We determined the response rate to and safety of a dual 5α-reductase inhibitor, dutasteride, in men with castration recurrent prostate cancer. Materials and Methods A total of 28 men with asymptomatic castration recurrent prostate cancer were treated with 3.5 mg dutasteride daily (luteinizing hormone-releasing hormone treatment continued), and evaluated monthly for response and toxicity. Eligibility included appropriate duration antiandrogen withdrawal, baseline prostate specific antigen 2.0 ng/ml or greater and a new lesion on bone scan, increase in measurable disease using Response Evaluation Criteria in Solid Tumors criteria, or 2 or more consecutive prostate specific antigen measurements increased over baseline. Outcomes were progression, stable disease, partial response (prostate specific antigen less than 50% of enrollment for 4 or more weeks) or complete response. Results There were 25 evaluable men with a mean age of 70 years (range 57 to 88), a mean prostate specific antigen of 61.9 ng/ml (range 5.0 to 488.9) and mean Gleason score 8 (range 6 to 10), 15 of whom had bone metastases. Eight men had 10 grade 3 or higher adverse events using National Cancer Institute Common Terminology Criteria, all of which were judged to be unrelated to treatment. Of the 25 men 14 had disease progression by 2 months, 9 had stable (2.5, 3, 3, 4, 4, 5, 5, 8.5, 9 months) disease, 2 had a partial response and none had a complete response. Overall median time to progression was 1.87 months (range 1 to 10, 95% CI 1.15–3.91). Conclusions Dutasteride rarely produces biochemical responses in men with castration recurrent prostate cancer. However, further study is warranted given its favorable safety profile. PMID:19091347

Disruption of Fibroblast Growth Factor Receptor (FGFR) Signaling as an Approach to Prostate Cancer Therapy

DTIC Science & Technology

2005-04-01

presented in tenth Annual Meeting of Association of Molecular Pathology and the abstract was published in the Journal of Molecular Diagnostics . The full...CDC25C Phosphatase Activity in Prostate Cancer: Correlation to Biochemical Recurrence. Journal of Molecular Diagnostics 2004, (6)4: 431. A manuscript in...receptor signaling. Clinical Cancer Research (in press). Acceptance letter for the above manuscript An abstract published in the Journal of Molecular

Functional Recovery, Oncologic Outcomes and Postoperative Complications after Robot-Assisted Radical Prostatectomy: An Evidence-Based Analysis Comparing the Retzius Sparing and Standard Approaches.

PubMed

Menon, Mani; Dalela, Deepansh; Jamil, Marcus; Diaz, Mireya; Tallman, Christopher; Abdollah, Firas; Sood, Akshay; Lehtola, Linda; Miller, David; Jeong, Wooju

2018-05-01

We report a 1-year update of functional urinary and sexual recovery, oncologic outcomes and postoperative complications in patients who completed a randomized controlled trial comparing posterior (Retzius sparing) with anterior robot-assisted radical prostatectomy. A total of 120 patients with clinically low-intermediate risk prostate cancer were randomized to undergo robot-assisted radical prostatectomy via the posterior and anterior approach in 60 each. Surgery was performed by a single surgical team at an academic institution. An independent third party ascertained urinary and sexual function outcomes preoperatively, and 3, 6 and 12 months after surgery. Oncologic outcomes consisted of positive surgical margins and biochemical recurrence-free survival. Biochemical recurrence was defined as 2 postoperative prostate specific antigen values of 0.2 ng/ml or greater. Median age of the cohort was 61 years and median followup was 12 months. At 12 months in the anterior vs posterior prostatectomy groups there were no statistically significant differences in the urinary continence rate (0 to 1 security pad per day in 93.3% vs 98.3%, p = 0.09), 24-hour pad weight (median 12 vs 7.5 gm, p = 0.3), erection sufficient for intercourse (69.2% vs 86.5%) or postoperative Sexual Health Inventory for Men score 17 or greater (44.6% vs 44.1%). In the posterior vs anterior prostatectomy groups a nonfocal positive surgical margin was found in 11.7% vs 8.3%, biochemical recurrence-free survival probability was 0.84 vs 0.93 and postoperative complications developed in 18.3% vs 11.7%. Among patients with clinically low-intermediate risk prostate cancer randomized to anterior (Menon) or posterior (Bocciardi) approach robot-assisted radical prostatectomy the differences in urinary continence seen at 3 months were muted at the 12-month followup. Sexual function recovery, postoperative complication and biochemical recurrence rates were comparable 1 year postoperatively. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prognostic value of saturated prostate cryoablation for localized prostate cancer.

PubMed

Chen, Chung-Hsin; Tai, Yi-Sheng; Pu, Yeong-Shiau

2015-10-01

To evaluate the oncological outcomes and complications of patients with saturated prostate cryoablation. A cohort of 208 patients cumulatively treated between June 2008 and December 2012 qualified for study inclusion, each undergoing total-gland cryoablation for prostate cancer. The degree of saturated prostate cryoablation was defined as the average prostate volume per cryoprobe (APVC), and divided into four groups (groups 1-4: <3 ml, 3 to <4 ml, 4 to <5 ml, ≧5 ml, respectively). Post-ablative complications were measured prospectively at weeks 1, 2, 4, 8, 12, and 24 by using the Common Terminology Criteria for Adverse Events. Biochemical failure was gauged by Phoenix criterion. The Kruskal-Wallis rank sum test and Chi-square test were used to compare clinical characteristics of therapeutic subsets. The Cox proportional hazard model was applied for comparison of recurrence risk between groups. APVC group 1 had the highest pre-operative PSA value and smallest prostate size among the groups. Multivariate analysis of risks of biochemical failures revealed that the larger the APVC, the higher the hazard (p for trend = 0.01). Compared to the group 1 patients, the hazard ratios of biochemical failures in groups 2-4 were 4.4 (confidence interval (CI): 0.5-37), 8.8 (CI 1.1-73), and 9.4 (CI 1.1-78), respectively. Nevertheless, the complication rate of APVC group 1 patients was similar to the other three groups. Saturated prostate cryoablation by reducing APVC would be beneficial for cancer control without compromising patient safety.

Percentage of positive prostate biopsies independently predicts biochemical outcome following radiation therapy for prostate cancer.

PubMed

Gabriele, Domenico; Garibaldi, Monica; Girelli, Giuseppe; Taraglio, Stefano; Duregon, Eleonora; Gabriele, Pietro; Guiot, Caterina; Bollito, Enrico

2016-06-01

This work aims to definitely show the ability of percentage of positive biopsy cores (%PC) to independently predict biochemical outcome beyond traditional pretreatment risk-factors in prostate cancer (PCa) patients treated with radiotherapy. A cohort of 2493 men belonging to the EUREKA-2 retrospective multicentric database on (PCa) and treated with external-beam radiation therapy (EBRT) as primary treatment comprised the study population (median follow-up 50 months). A Cox regression time to prostate-specific antigen (PSA) failure analysis was performed to evaluate the predictive power of %PC, both in univariate and multivariate settings, with age, pretreatment PSA, clinical-radiological staging, bioptic Gleason Score (bGS), RT dose and RT +/- ADT as covariates. P statistics for %PC is lower than 0.001 both in univariate and multivariate models. %PC as a continuous variable yields an AUC of 69% in ROC curve analysis for biochemical relapse. Four classes of %PC (1-20%, 21-50%, 51-80% and 81-100%) distinctly split patients for risk of biochemical relapse (overall log-rank test P<0.0001), with biochemical progression free survival (bPFS) at 5-years ranging from 88% to 58% and 10-years bPFS ranging from 80% to 38%. We strongly affirm the usefulness of %PC information beyond main risk factors (PSA, staging and bGS) in predicting biochemical recurrence after EBRT for PCa. The stratification of patients according to %PC may be valuable to further discriminate cases with favourable or adverse prognosis.

MRI evaluation following partial HIFU therapy for localized prostate cancer: A single-center study.

PubMed

Hoquetis, L; Malavaud, B; Game, X; Beauval, J B; Portalez, D; Soulie, M; Rischmann, P

2016-09-01

To evaluate the value of MRI for surveillance of primary hemi-HIFU therapy for localized PCa in a single-center. Patients with localized prostate cancer were treated with hemi-HIFU from October 2009 to March 2014. All patients performed MRI before focal therapy, the reader was blinded to the treatment. Oncological failure was defined as positive biopsy or biochemical recurrence (Phoenix). Twenty-five patients were treated with hemi-HIFU in one center. The median nadir PSA was 1.45±1.4ng/mL. Prostate volume decreased from 45 cc to 25 cc on MRI findings. At 20 months, none of the patients had histological recurrence. Biochemical-free survival rate was 88%. MRI evaluation had a negative predictive value of 100% on the treated area and 81% on the untreated area. PSAd≥0.1ng/mL(2) was a predictive factor for cancer on untreated area (P=0.042). MRI control at 6 months is a potentially effective evaluation of treated area after hemi-HIFU and may replace randomized biopsies if PSAd<0.1ng/mL(2) during follow-up. 4. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Effect of Sulforaphane in Men with Biochemical Recurrence after Radical Prostatectomy.

PubMed

Cipolla, Bernard G; Mandron, Eric; Lefort, Jean Marc; Coadou, Yves; Della Negra, Emmanuel; Corbel, Luc; Le Scodan, Ronan; Azzouzi, Abdel Rahmene; Mottet, Nicolas

2015-08-01

Increases in serum levels of prostate-specific antigen (PSA) occur commonly in prostate cancer after radical prostatectomy and are designated "biochemical recurrence." Because the phytochemical sulforaphane has been studied extensively as an anticancer agent, we performed a double-blinded, randomized, placebo-controlled multicenter trial with sulforaphane in 78 patients (mean age, 69 ± 6 years) with increasing PSA levels after radical prostatectomy. Treatment comprised daily oral administration of 60 mg of a stabilized free sulforaphane for 6 months (M0-M6) followed by 2 months without treatment (M6-M8). The study was designed to detect a 0.012 log (ng/mL)/month decrease in the log PSA slope in the sulforaphane group from M0 to M6. The primary endpoint was not reached. For secondary endpoints, median log PSA slopes were consistently lower in sulforaphane-treated men. Mean changes in PSA levels between M6 and M0 were significantly lower in the sulforaphane group (+0.099 ± 0.341 ng/mL) than in placebo (+0.620 ± 1.417 ng/mL; P = 0.0433). PSA doubling time was 86% longer in the sulforaphane than in the placebo group (28.9 and 15.5 months, respectively). PSA increases >20% at M6 were significantly greater in the placebo group (71.8%) than in the sulforaphane group (44.4%); P = 0.0163. Compliance and tolerance were very good. Sulforaphane effects were prominent after 3 months of intervention (M3-M6). After treatment, PSA slopes from M6 to M8 remained the same in the 2 arms. Daily administration of free sulforaphane shows promise in managing biochemical recurrences in prostate cancer after radical prostatectomy. ©2015 American Association for Cancer Research.

Prognostic relevance of proliferation markers (Ki-67, PHH3) within the cross-relation of ERG translocation and androgen receptor expression in prostate cancer.

PubMed

Goltz, Diane; Montani, Matteo; Braun, Martin; Perner, Sven; Wernert, Nicolas; Jung, Klaus; Dietel, Manfred; Stephan, Carsten; Kristiansen, Glen

2015-12-01

We evaluated the prognostic value of the mitosis-associated marker phosphorylated histone H3 (PHH3) and Ki-67 in prostate cancer with respect to ERG status and androgen receptor (AR) expression.PHH3 and Ki-67 expression was immunohistochemically detected and digitally quantitated in a radical prostatectomy cohort (n = 640). The results were correlated to clinicopathological parameters including biochemical recurrence times. Prognostic values of PHH3 and Ki-67 were analysed by Cox regression and Kaplan-Meier statistics.In prostate cancer, mean Ki-67 and PHH3 rates were 3.40% (95%CI 3.16-3.63%) and 0.0152% (95%CI 0.0112-0.0191%), respectively.Ki-67 showed a significant correlation with Gleason scores, pT status, margin status, and AR expression, while PHH3 showed a significant correlation with Gleason scores and pT status. Univariate analyses for biochemical recurrence times demonstrated a significant prognostic value for median Ki-67 rate and for the PHH3 rate of the 90th percentile. Of importance, in patient subgroups stratified according to AR expression and ERG translocation, the prognostic power of proliferation markers PHH3 and Ki-67 was markedly enhanced in ERG translocation negative and high-level AR expressing ERG translocation positive prostate cancers.As expected, the proliferation markers PHH3 and Ki-67 predict adverse outcome of prostate cancer and have a particularly pronounced prognostic value in specific molecular subsets of prostate cancer (ERG- or AR+).

DNA-PKcs Expression Is a Predictor of Biochemical Recurrence After Permanent Iodine 125 Interstitial Brachytherapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Molina, Sarah; Department of Radiation Oncology, CHU/Université de Poitiers, Poitiers; Guerif, Stéphane

Purpose: Predictive factors for biochemical recurrence (BCR) in localized prostate cancer (PCa) after brachytherapy are insufficient to date. Cellular radiosensitivity depends on DNA double-strand breaks, mainly repaired by the nonhomologous end-joining (NHEJ) system. We analyzed whether the expression of NHEJ proteins can predict BCR in patients treated by brachytherapy for localized PCa. Methods and Materials: From 983 PCa cases treated by brachytherapy between March 2000 and March 2012, 167 patients with available biopsy material suitable for in situ analysis were included in the study. The median follow-up time was 47 months. Twenty-nine patients experienced BCR. All slides were reviewed to reassessmore » the Gleason score. Expression of the key NHEJ proteins DNA-PKcs, Ku70, and Ku80, and the proliferation marker Ki67, was studied by immunohistochemistry performed on tissue microarrays. Results: The Gleason scores after review (P=.06) tended to be associated with BCR when compared with the score initially reported (P=.74). Both the clinical stage (P=.02) and the pretreatment prostate-specific antigen level (P=.01) were associated with biochemical failure. Whereas the expression of Ku80 and Ki67 were not predictive of relapse, positive DNA-PKcs nuclear staining (P=.003) and higher Ku70 expression (P=.05) were associated with BCR. On multivariate analysis, among pretreatment variables, only DNA-PKcs (P=.03) and clinical stage (P=.02) remained predictive of recurrence. None of the patients without palpable PCa and negative DNA-PKcs expression experienced biochemical failure, compared with 32% of men with palpable and positive DNA-PKcs staining that recurred. Conclusions: Our results suggest that DNA-PKcs could be a predictive marker of BCR after brachytherapy, and this might be a useful tool for optimizing the choice of treatment in low-risk PCa patients.« less

The role of prostate-specific antigen in light of new scientific evidence.

PubMed

Hernández, C; Morote, J; Miñana, B; Cózar, J M

2013-06-01

Review the scientific evidence acquired in recent years on Prostate-Specific Antigen (PSA). Analysis of the available evidence on the current role of PSA, according to a panel of experts who recorded their experience on the subject. Currently, PSA cannot be considered solely an indicator of the presence or absence of prostate cancer. Rather, the determination of PSA assists the urologist in indicating the most appropriate treatment for a patient with benign prostatic hypertrophic (BPH), as well as in suspecting a prostatic tumour when the PSA reading increases >0,3 ng/ml, in patients treated with 5-alpha-reductase inhibitor, over the reading achieved at six months of having initiated this treatment. Moreover, PSA is a key factor in the follow-up of patients with prostate adenocarcinoma who undergo surgery, radiation therapy or minimally invasive techniques. PSA helps to define biochemical recurrence, suggest the existence of a local or distal recurrence and propose or rule out adjuvant therapies. New data on the current role of PSA in the management of patients treated for BPH and/or prostate cancer should be taken into account. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Impact of a preoperatively estimated prostate volume using transrectal ultrasonography on surgical and oncological outcomes in a single surgeon's experience with robot-assisted radical prostatectomy.

PubMed

Hirasawa, Yosuke; Ohno, Yoshio; Nakashima, Jun; Shimodaira, Kenji; Hashimoto, Takeshi; Gondo, Tatsuo; Ohori, Makoto; Tachibana, Masaaki; Yoshioka, Kunihiko

2016-09-01

To assess the impact of preoperatively estimated prostate volume (PV) using transrectal ultrasonography (TRUS) on surgical and oncological outcomes in robot-assisted radical prostatectomy (RARP). We analyzed the experience of a single surgeon at our hospital who performed 436 RARPs without neoadjuvant hormone therapy between August 2006 and December 2013. Patients were divided into three groups according to their preoperative PV calculated using TRUS (PV ≤ 20 cm(3): group 1, n = 61; 20 < PV < 50 cm(3): group 2, n = 303; PV ≥ 50 cm(3): group 3, n = 72). Blood loss was significantly higher in group 3 than in group 1 and group 2. In stage pT2 patients, the rate of positive surgical margin (PSM) was significantly lower in group 3 than in group 1. In addition, perioperative complications significantly increased with increasing PV, while the extraprostatic extension (EPE) rate significantly decreased with increasing PV. The preoperative biopsy Gleason score, prostate-specific antigen (PSA) density, and clinical T2 stage were inversely correlated with increasing PV. Biochemical recurrence-free survival after RARP was significantly lower in group 1 than in groups 2 and 3. A large prostate size was significantly associated with increased blood loss and a higher rate of perioperative complications. A small prostate size was associated with a higher PSM rate, PSA density, Gleason score, EPE rate, and biochemical recurrence rate. These results suggest that RARP was technically challenging in patients with large prostates, whereas small prostates were associated with unfavorable oncological outcomes.

Salvage prostate re-irradiation using high-dose-rate brachytherapy or focal stereotactic body radiotherapy for local recurrence after definitive radiation therapy.

PubMed

Mbeutcha, Aurélie; Chauveinc, Laurent; Bondiau, Pierre-Yves; Chand, Marie-Eve; Durand, Matthieu; Chevallier, Daniel; Amiel, Jean; Kee, Daniel Lam Cham; Hannoun-Lévi, Jean-Michel

2017-03-09

Optimal management of locally recurrent prostate cancer after definitive radiation therapy is still challenging. With the development of highly accurate radiotherapy devices, prostate salvage re-irradiation might generate lower toxicity rates than classical salvage therapies. We retrospectively evaluated the toxicity and the feasibility of a prostate re-irradiation after definitive radiation therapy failure. Two modalities were investigated: high-dose-rate brachytherapy (HDRB) on whole prostate gland and focal stereotactic radiotherapy (SBRT) using CyberKnife® linac. Between 2011 and 2015, 28 patients with imaged and/or biopsy-proven intra-prostatic recurrence of cancer after definitive radiation therapy underwent a salvage re-irradiation using HDRB (n = 10) or focal SBRT (n = 18). The schedule of re-irradiation was 35 Gy in 5 fractions. Biological response (defined as post-salvage radiation PSA variation) and biochemical no-evidence of disease (bNED) were evaluated in the whole cohort. For patients who had a positive biological response after salvage radiation, biochemical recurrence (BCR) and survival after salvage radiotherapy were evaluated. Post-salvage toxicities were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 and were compared to baseline status. Within a median follow-up of 22.5 months (IQR = 8-42), 9 (90%) patients experienced a positive biological response after salvage HDRB and 5 (50%) remained bNED at the end of the follow-up. Among patients who initially responded to salvage HDRB, the BCR rate was 44.4% after a median interval of 19.5 months (IQR = 11.5-26). Only one patient experienced a transient grade 3 urinary complication. In the SBRT group, the median follow-up was 14.5 months (IQR = 7-23) and 10 (55.6%) out of the 18 patients remained bNED. Among the 15 patients who initially responded to salvage SBRT, 5 (33.3%) experienced a BCR. One patient experienced a transient grade 4 urinary complication. At the end of the follow-up, all evaluated patients had a urinary status grade variation ≤ +1 grade. No grade 3-4 digestive toxicity was observed. Salvage prostate re-irradiation for locally recurrent cancer is feasible and generate low toxicities rates when using with HDRB or focal SBRT. However, further investigations are necessary to confirm these findings and to determine predictive features for patients who might benefit from such an approach.

Changes in lower urinary tract symptoms and quality of life after salvage radiotherapy for biochemical recurrence of prostate cancer.

PubMed

Miyake, Makito; Tanaka, Nobumichi; Asakawa, Isao; Tatsumi, Yoshihiro; Nakai, Yasushi; Anai, Satoshi; Torimoto, Kazumasa; Aoki, Katsuya; Yoneda, Tatsuo; Hasegawa, Masatoshi; Konishi, Noboru; Fujimoto, Kiyohide

2015-06-01

The aim of this study was to evaluate chronologic changes in lower urinary tract symptoms (LUTS), health-related (HR) quality of life (QOL), and disease-specific QOL during the first 12 months after salvage radiotherapy (SRT) for biochemical recurrence of prostate cancer in patients who underwent radical prostatectomy. In 81 patients who received SRT (70 Gy/35fr/7 weeks), International Prostate Symptom Score (IPSS), 36-Item Short Form scores, and UCLA-Prostate Cancer Index (UCLA-PCI) were recorded before, during, and immediately after SRT, and 1-12 months after the completion of SRT. The total IPSS and storage symptom-related sum were significantly increased following initiation of SRT, and returned to the baseline 6 months after SRT. For three of eight domains of HRQOL, and the physical component summary score showed transient deterioration in the period between completion of SRT and 1 month following SRT. The UCLA-PCI for urinary function/bother and bowel function/bother was affected until 1-6 months after SRT. This is the first report to concurrently evaluate detailed chronologic changes in LUTS and QOL in patients who received SRT. Knowledge of changes in LUTS and QOL outcomes associated with SRT may influence treatment recommendations and enable patients to make better-informed decisions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Global transcriptome analysis of formalin-fixed prostate cancer specimens identifies biomarkers of disease recurrence.

PubMed

Long, Qi; Xu, Jianpeng; Osunkoya, Adeboye O; Sannigrahi, Soma; Johnson, Brent A; Zhou, Wei; Gillespie, Theresa; Park, Jong Y; Nam, Robert K; Sugar, Linda; Stanimirovic, Aleksandra; Seth, Arun K; Petros, John A; Moreno, Carlos S

2014-06-15

Prostate cancer remains the second leading cause of cancer death in American men and there is an unmet need for biomarkers to identify patients with aggressive disease. In an effort to identify biomarkers of recurrence, we performed global RNA sequencing on 106 formalin-fixed, paraffin-embedded prostatectomy samples from 100 patients at three independent sites, defining a 24-gene signature panel. The 24 genes in this panel function in cell-cycle progression, angiogenesis, hypoxia, apoptosis, PI3K signaling, steroid metabolism, translation, chromatin modification, and transcription. Sixteen genes have been associated with cancer, with five specifically associated with prostate cancer (BTG2, IGFBP3, SIRT1, MXI1, and FDPS). Validation was performed on an independent publicly available dataset of 140 patients, where the new signature panel outperformed markers published previously in terms of predicting biochemical recurrence. Our work also identified differences in gene expression between Gleason pattern 4 + 3 and 3 + 4 tumors, including several genes involved in the epithelial-to-mesenchymal transition and developmental pathways. Overall, this study defines a novel biomarker panel that has the potential to improve the clinical management of prostate cancer. ©2014 American Association for Cancer Research.

L-dopa decarboxylase (DDC) gene expression is related to outcome in patients with prostate cancer.

PubMed

Koutalellis, Georgios; Stravodimos, Konstantinos; Avgeris, Margaritis; Mavridis, Konstantinos; Scorilas, Andreas; Lazaris, Andreas; Constantinides, Constantinos

2012-09-01

What's known on the subject? and What does the study add? L-dopa decarboxylase (DDC) has been documented as a novel co-activator of androgen receptor transcriptional activity. Recently, it was shown that DDC gene expression is significantly higher in patients with PCa than in those with BPH. In the present study, there was a significant association between the DDC gene expression levels and the pathological stage and Gleason score of patients with prostate cancer (PCa). Moreover, DDC expression was shown to be an unfavourable prognostic marker of biochemical recurrence and disease-free survival in patients with PCa treated by radical prostatectomy. To determine whether L-dopa decarboxylase gene (DDC) expression levels in patients with prostate cancer (PCa) correlate to biochemical recurrence and disease prognosis after radical prostatectomy (RP). The present study consisted of 56 samples with confirmed malignancy from patients with PCa who had undergone RP at a single tertiary academic centre. Total RNA was isolated from tissue specimens and a SYBR Green fluorescence-based quantitative real-time polymerase chain reaction methodology was developed for the determination of DDC mRNA expression levels of the tested tissues. Follow-up time ranged between 1.0 and 62.0 months (mean ± SE, 28.6 ± 2.1 month; median, 31.5 months). Time to biochemical recurrence was defined as the interval between the surgery and the measurement of two consecutive values of prostate-specific antigen (PSA) ≥0.2 ng/mL. DDC expression levels were found to be positively correlated with the tumour-node-metastasis stage (P = 0.021) and Gleason score (P = 0.036) of the patients with PCa. Patients with PCa with raised DDC expression levels run a significantly higher risk of biochemical recurrence after RP, as indicated by Cox proportional regression analysis (P = 0.021). Multivariate Cox proportional regression models revealed the preoperative PSA-, age- and digital rectal examination-independent prognostic value of DDC expression for the prediction of disease-free survival (DFS) among patients with PCa (P = 0.036). Kaplan-Meier survival analysis confirms the significantly shorter DFS after RP of PCa with higher DDC expression levels (P = 0.015). This is the first study indicating the potential of DDC expression as a novel prognostic biomarker in patients with PCa who have undergone RP. For further evaluation and clinical application of the findings of the present study, a direct analysis of mRNA and/or its protein expression level in preoperative biopsy, blood serum and urine should be conducted. © 2012 BJU INTERNATIONAL.

Tumor suppressor function of PGP9.5 is associated with epigenetic regulation in prostate cancer--novel predictor of biochemical recurrence after radical surgery.

PubMed

Mitsui, Yozo; Shiina, Hiroaki; Hiraki, Miho; Arichi, Naoko; Hiraoka, Takeo; Sumura, Masahiro; Honda, Satoshi; Yasumoto, Hiroaki; Igawa, Mikio

2012-03-01

The expression level of protein G product 9.5 (PGP9.5) is downregulated because of promoter CpG hypermethylation in several tumors. We speculated that impaired regulation of PGP9.5 through epigenetic pathways is associated with the pathogenesis of prostate cancer. CpG methylation of the PGP9.5 gene was analyzed in cultured prostate cancer cell lines, 226 localized prostate cancer samples from radical prostatectomy cases, and 80 benign prostate hyperplasia (BPH) tissues. Following 5-aza-2'-deoxycytidune treatment, increased PGP9.5 mRNA transcript expression was found in the LNCaP and PC3 cell lines. With bisulfite DNA sequencing, partial methylation of the PGP9.5 promoter was shown in LNCaP whereas complete methylation was found in PC3 cells. After transfection of PGP9.5 siRNA, cell viability was significantly accelerated in LNCaP but not in PC3 cells as compared with control siRNA transfection. Promoter methylation of PGP9.5 was extremely low in only one of 80 BPH tissues, whereas it was found in 37 of 226 prostate cancer tissues. Expression of the mRNA transcript of PGP9.5 was significantly lower in methylation (+) than methylation (-) prostate cancer tissues. Multivariate analysis of biochemical recurrence (BCR) after an radical prostatectomy revealed pT category and PGP9.5 methylation as prognostically relevant. Further stratification with the pT category in addition to methylation status identified a stepwise reduction of BCR-free probability. This is the first clinical and comprehensive study of inactivation of the PGP9.5 gene via epigenetic pathways in primary prostate cancer. CpG methylation of PGP9.5 in primary prostate cancer might become useful as a molecular marker for early clinical prediction of BCR after radical prostatectomy. ©2012 AACR.

Promoter methylation of the immune checkpoint receptor PD-1 (PDCD1) is an independent prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy

PubMed Central

Goltz, Diane; Gevensleben, Heidrun; Dietrich, Jörn; Ellinger, Jörg; Landsberg, Jennifer; Kristiansen, Glen; Dietrich, Dimo

2016-01-01

ABSTRACT Biomarkers that facilitate the prediction of disease recurrence in prostate cancer (PCa) may enable physicians to personalize treatment for individual patients. In the current study, PD-1 (PDCD1) promoter methylation was assessed in a cohort of 498 PCa patients included in The Cancer Genome Atlas (TCGA) and a second cohort of 300 PCa cases treated at the University Hospital of Bonn. In the TCGA cohort, the PD-1 promoter was significantly hypermethylated in carcinomas versus normal prostatic epithelium (55.5% vs. 38.2%, p < 0.001) and PD-1 methylation (mPD-1) inversely correlated with PD-1 mRNA expression in PCa (Spearman's ρ = −0.415, p < 0.001). In both cohorts, mPD-1 significantly correlated with preoperative prostate specific antigen (PSA). In univariate Cox Proportional Hazard analysis, mPD-1 served as a significant prognostic factor for biochemical recurrence (BCR)-free survival (Hazard ratio: HR = 2.35 [1.35–4.10], p = 0.003, n = 410) in the TCGA cohort. In multivariate analysis, mPD-1 was shown to add significant independent prognostic information adjunct to pathologic tumor category (pT) and Gleason grading group (HR = 2.08 [1.16–3.74], p = 0.014, n = 350). PD-1 promoter methylation analyses could thus potentially aid the identification of patients which might benefit from adjuvant treatment after radical prostatectomy. Moreover, our data suggest an intrinsic role of PD-1 in PCa carcinogenesis and disease progression, which needs to be addressed in future studies. PMID:27853645

Comparison of 18F-FACBC and 11C-choline PET/CT in patients with radically treated prostate cancer and biochemical relapse: preliminary results.

PubMed

Nanni, Cristina; Schiavina, Riccardo; Boschi, Stefano; Ambrosini, Valentina; Pettinato, Cinzia; Brunocilla, Eugenio; Martorana, Giuseppe; Fanti, Stefano

2013-07-01

We assessed the rate of detection rate of recurrent prostate cancer by PET/CT using anti-3-(18)F-FACBC, a new synthetic amino acid, in comparison to that using (11)C-choline as part of an ongoing prospective single-centre study. Included in the study were 15 patients with biochemical relapse after initial radical treatment of prostate cancer. All the patients underwent anti-3-(18)F-FACBC PET/CT and (11)C-choline PET/CT within a 7-day period. The detection rates using the two compounds were determined and the target-to-background ratios (TBR) of each lesion are reported. No adverse reactions to anti-3-(18)F-FACBC PET/CT were noted. On a patient basis, (11)C-choline PET/CT was positive in 3 patients and negative in 12 (detection rate 20%), and anti-3-(18)F-FACBC PET/CT was positive in 6 patients and negative in 9 (detection rate 40%). On a lesion basis, (11)C-choline detected 6 lesions (4 bone, 1 lymph node, 1 local relapse), and anti-3-(18)F-FACBC detected 11 lesions (5 bone, 5 lymph node, 1 local relapse). All (11)C-choline-positive lesions were also identified by anti-3-(18)F-FACBC PET/CT. The TBR of anti-3-(18)F-FACBC was greater than that of (11)C-choline in 8/11 lesions, as were image quality and contrast. Our preliminary results indicate that anti-3-(18)F-FACBC may be superior to (11)C-choline for the identification of disease recurrence in the setting of biochemical failure. Further studies are required to assess efficacy of anti-3-(18)F-FACBC in a larger series of prostate cancer patients.

Phase 1 trial of neoadjuvant radiation therapy before prostatectomy for high-risk prostate cancer.

PubMed

Koontz, Bridget F; Quaranta, Brian P; Pura, John A; Lee, W R; Vujaskovic, Zeljko; Gerber, Leah; Haake, Michael; Anscher, Mitchell S; Robertson, Cary N; Polascik, Thomas J; Moul, Judd W

2013-09-01

To evaluate, in a phase 1 study, the safety of neoadjuvant whole-pelvis radiation therapy (RT) administered immediately before radical prostatectomy in men with high-risk prostate cancer. Twelve men enrolled and completed a phase 1 single-institution trial between 2006 and 2010. Eligibility required a previously untreated diagnosis of localized but high-risk prostate cancer. Median follow-up was 46 months (range, 14-74 months). Radiation therapy was dose-escalated in a 3 × 3 design with dose levels of 39.6, 45, 50.4, and 54 Gy. The pelvic lymph nodes were treated up to 45 Gy with any additional dose given to the prostate and seminal vesicles. Radical prostatectomy was performed 4-8 weeks after RT completion. Primary outcome measure was intraoperative and postoperative day-30 morbidity. Secondary measures included late morbidity and oncologic outcomes. No intraoperative morbidity was seen. Chronic urinary grade 2+ toxicity occurred in 42%; 2 patients (17%) developed a symptomatic urethral stricture requiring dilation. Two-year actuarial biochemical recurrence-free survival was 67% (95% confidence interval 34%-86%). Patients with pT3 or positive surgical margin treated with neoadjuvant RT had a trend for improved biochemical recurrence-free survival compared with a historical cohort with similar adverse factors. Neoadjuvant RT is feasible with moderate urinary morbidity. However, oncologic outcomes do not seem to be substantially different from those with selective postoperative RT. If this multimodal approach is further evaluated in a phase 2 setting, 54 Gy should be used in combination with neoadjuvant androgen deprivation therapy to improve biochemical outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

Reduction in expression of the benign AR transcriptome is a hallmark of localised prostate cancer progression.

PubMed

Stuchbery, Ryan; Macintyre, Geoff; Cmero, Marek; Harewood, Laurence M; Peters, Justin S; Costello, Anthony J; Hovens, Christopher M; Corcoran, Niall M

2016-05-24

Despite the importance of androgen receptor (AR) signalling to prostate cancer development, little is known about how this signalling pathway changes with increasing grade and stage of the disease. To explore changes in the normal AR transcriptome in localised prostate cancer, and its relation to adverse pathological features and disease recurrence. Publically accessible human prostate cancer expression arrays as well as RNA sequencing data from the prostate TCGA. Tumour associated PSA and PSAD were calculated for a large cohort of men (n=1108) undergoing prostatectomy. We performed a meta-analysis of the expression of an androgen-regulated gene set across datasets using Oncomine. Differential expression of selected genes in the prostate TCGA database was probed using the edgeR Bioconductor package. Changes in tumour PSA density with stage and grade were assessed by Student's t-test, and its association with biochemical recurrence explored by Kaplan-Meier curves and Cox regression. Meta-analysis revealed a systematic decline in the expression of a previously identified benign prostate androgen-regulated gene set with increasing tumour grade, reaching significance in nine of 25 genes tested despite increasing AR expression. These results were confirmed in a large independent dataset from the TCGA. At the protein level, when serum PSA was corrected for tumour volume, significantly lower levels were observed with increasing tumour grade and stage, and predicted disease recurrence. Lower PSA secretion-per-tumour-volume is associated with increasing grade and stage of prostate cancer, has prognostic relevance, and reflects a systematic perturbation of androgen signalling.

Clinical impact of PSMA-based 18F-DCFBC PET/CT imaging in patients with biochemically recurrent prostate cancer after primary local therapy.

PubMed

Mena, Esther; Lindenberg, Maria L; Shih, Joanna H; Adler, Stephen; Harmon, Stephanie; Bergvall, Ethan; Citrin, Deborah; Dahut, William; Ton, Anita T; McKinney, Yolanda; Weaver, Juanita; Eclarinal, Philip; Forest, Alicia; Afari, George; Bhattacharyya, Sibaprasad; Mease, Ronnie C; Merino, Maria J; Pinto, Peter; Wood, Bradford J; Jacobs, Paula; Pomper, Martin G; Choyke, Peter L; Turkbey, Baris

2018-01-01

The purpose of our study was to assess 18 F-DCFBC PET/CT, a PSMA targeted PET agent, for lesion detection and clinical management of biochemical relapse in prostate cancer patients after primary treatment. This is a prospective IRB-approved study of 68 patients with documented biochemical recurrence after primary local therapy consisting of radical prostatectomy (n = 50), post radiation therapy (n = 9) or both (n = 9), with negative conventional imaging. All 68 patients underwent whole-body 18 F-DCFBC PET/CT, and 62 also underwent mpMRI within one month. Lesion detection with 18 F-DCFBC was correlated with mpMRI findings and pre-scan PSA levels. The impact of 18 F-DCFBC PET/CT on clinical management and treatment decisions was established after 6 months' patient clinical follow-up. Forty-one patients (60.3%) showed at least one positive 18 F-DCFBC lesion, for a total of 79 lesions, 30 in the prostate bed, 39 in lymph nodes, and ten in distant sites. Tumor recurrence was confirmed by either biopsy (13/41 pts), serial CT/MRI (8/41) or clinical follow-up (15/41); there was no confirmation in five patients, who continue to be observed. The 18 F-DCFBC and mpMRI findings were concordant in 39 lesions (49.4%), and discordant in 40 lesions (50.6%); the majority (n = 32/40) of the latter occurring because the recurrence was located outside the mpMRI field of view. 18 F-DCFBC PET positivity rates correlated with PSA values and 15%, 46%, 83%, and 77% were seen in patients with PSA values <0.5, 0.5 to <1.0, 1.0 to <2.0, and ≥2.0 ng/mL, respectively. The optimal cut-off PSA value to predict a positive 18 F-DCFBC scan was 0.78 ng/mL (AUC = 0.764). A change in clinical management occurred in 51.2% (21/41) of patients with a positive 18 F-DCFBC result, generally characterized by starting a new treatment in 19 patients or changing the treatment plan in two patients. 18 F-DCFBC detects recurrences in 60.3% of a population of patients with biochemical recurrence, but results are dependent on PSA levels. Above a threshold PSA value of 0.78 ng/mL, 18 F-DCFBC was able to identify recurrence with high reliability. Positive 18 F-DCFBC PET imaging led clinicians to change treatment strategy in 51.2% of patients.

High-dose-rate stereotactic body radiation therapy for postradiation therapy locally recurrent prostatic carcinoma: Preliminary prostate-specific antigen response, disease-free survival, and toxicity assessment.

PubMed

Fuller, Donald B; Wurzer, James; Shirazi, Reza; Bridge, Stephen S; Law, Jonathan; Mardirossian, George

2015-01-01

Patients with locally recurrent adenocarcinoma of the prostate following radiation therapy (RT) present a challenging problem. We prospectively evaluated the use of "high-dose-rate-like" prostate stereotactic body RT (SBRT) salvage for this circumstance, evaluating prostate-specific antigen response, disease-free survival, and toxicity. Between February 2009 and March 2014, 29 patients with biopsy-proven recurrent locally prostate cancer >2 years post-RT were treated. Median prior RT dose was 73.8 Gy and median interval to SBRT salvage was 88 months. Median recurrence Gleason score was 7 (79% was ≥7). Pre-existing RT toxicity >grade 1 was a reason for exclusion. Magnetic resonance imaging-defined prostate volume including any suspected extraprostatic extension, comprising the planning target volume. A total of 34 Gy/5 fractions was given, delivering a heterogeneous, high-dose-rate-like dose-escalation pattern. Toxicities were assessed using Common Terminology Criteria for Adverse Events, version 3.0, criteria. Twenty-nine treated patients had a median 24-month follow-up (range, 3-60 months). A median pre-SBRT salvage baseline prostate-specific antigen level of 3.1 ng/mL decreased to 0.65 ng/mL and 0.16 ng/mL at 1 and 2 years, respectively. Actuarial 2-year biochemical disease-free survival measured 82%, with no local failures. Toxicity >grade 1 was limited to the genitourinary domain, with 18% grade 2 or higher and 7% grade 3 or higher. No gastrointestinal toxicity >grade 1 occurred. Two-year disease-free survival is encouraging, and the prostate-specific antigen response kinetic appears comparable with that seen in de novo patients treated with SBRT, albeit still a preliminary finding. Grade ≥2 genitourinary toxicity was occasionally seen with no obvious predictive factor. Noting that our only brachytherapy case was 1 of the 2 cases with ≥grade 3 genitourinary toxicity, caution is recommended treating these patients. SBRT salvage of post-RT local recurrence appears clinically feasible, with longer term evaluation required to assess ultimate efficacy and late toxicity rates. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Pubic Bone Osteomyelitis after Salvage High-Intensity Focused Ultrasound for Prostate Cancer

PubMed Central

Robison, Christopher M.; Gor, Ronak A.; Metro, Michael J.

2014-01-01

High-intensity focused ultrasound can be used for the primary treatment of prostate cancer and biochemical recurrence after radical prostatectomy or radiation. Complications of high-intensity focused ultrasound include urinary retention, urethral stenosis, stress incontinence, urinary tract infections, dysuria, impotence, and rarely, rectourethral or rectovesicular fistula. We describe a patient presenting with urinary retention, urinary tract infections and intermittent stress incontinence, later found to be associated with pubic bone osteomyelitis stemming from a prostatopubic fistula. PMID:24917777

External Beam Radiotherapy Affects Serum Testosterone in Patients With Localized Prostate Cancer.

PubMed

Pompe, Raisa S; Karakiewicz, Pierre I; Zaffuto, Emanuele; Smith, Ariane; Bandini, Marco; Marchioni, Michele; Tian, Zhe; Leyh-Bannurah, Sami-Ramzi; Schiffmann, Jonas; Delouya, Guila; Lambert, Carole; Bahary, Jean-Paul; Beauchemin, Marie Claude; Barkati, Maroie; Ménard, Cynthia; Graefen, Markus; Saad, Fred; Tilki, Derya; Taussky, Daniel

2017-07-01

Previous studies have examined testosterone levels after external beam radiation (EBRT) monotherapy, but since 2002 only sparse contemporary data have been reported. To examine testosterone kinetics in a large series of contemporary patients after EBRT. The study was conducted in 425 patients who underwent definitive EBRT for localized prostate cancer from 2002 through 2014. Patients were enrolled in several phase II and III trials. Exclusion criteria were neoadjuvant or adjuvant androgen-deprivation therapy or missing data. Testosterone was recorded at baseline and then according to each study protocol (not mandatory in all protocols). Statistical analyses consisted of means and proportions, Kaplan-Meier plots, and logistic and Cox regression analyses. Testosterone kinetics after EBRT monotherapy and their influence on biochemical recurrence. Median follow-up of 248 assessable patients was 72 months. One hundred eighty-six patients (75.0%) showed a decrease in testosterone. Median time to first decrease was 6.4 months. Median percentage of decrease to the nadir was 30% and 112 (45.2%) developed biochemical hypogonadism (serum testosterone < 8 nmol/L). Of all patients with testosterone decrease, 117 (62.9%) recovered to at least 90% of baseline levels. Advanced age, increased body mass index, higher baseline testosterone level, and lower nadir level were associated with a lower chance of testosterone recovery. Subgroup analyses of 166 patients treated with intensity-modulated radiotherapy confirmed the results recorded for the entire cohort. In survival analyses, neither testosterone decrease nor recovery was predictive for biochemical recurrence. EBRT monotherapy influences testosterone kinetics, and although most patients will recover, approximately 45% will have biochemical hypogonadism. We report on the largest contemporary series of patients treated with EBRT monotherapy in whom testosterone kinetics were ascertained. Limitations are that testosterone follow-up was not uniform and the study lacked information on health-related quality-of-life data. Our findings indicate that up to 75% of patients will have a profound testosterone decrease, with up to a 40% increase in rates of biochemical hypogonadism, although the latter events will leave biochemical recurrence unaffected. Pompe RS, Karakrewicz PI, Zaffuto E, et al. External Beam Radiotherapy Affects Serum Testosterone in Patients With Localized Prostate Cancer. J Sex Med 2017;14:876-882. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Evaluating stability of histomorphometric features across scanner and staining variations: predicting biochemical recurrence from prostate cancer whole slide images

NASA Astrophysics Data System (ADS)

Leo, Patrick; Lee, George; Madabhushi, Anant

2016-03-01

Quantitative histomorphometry (QH) is the process of computerized extraction of features from digitized tissue slide images. Typically these features are used in machine learning classifiers to predict disease presence, behavior and outcome. Successful robust classifiers require features that both discriminate between classes of interest and are stable across data from multiple sites. Feature stability may be compromised by variation in slide staining and scanning procedures. These laboratory specific variables include dye batch, slice thickness and the whole slide scanner used to digitize the slide. The key therefore is to be able to identify features that are not only discriminating between the classes of interest (e.g. cancer and non-cancer or biochemical recurrence and non- recurrence) but also features that will not wildly fluctuate on slides representing the same tissue class but from across multiple different labs and sites. While there has been some recent efforts at understanding feature stability in the context of radiomics applications (i.e. feature analysis of radiographic images), relatively few attempts have been made at studying the trade-off between feature stability and discriminability for histomorphometric and digital pathology applications. In this paper we present two new measures, preparation-induced instability score (PI) and latent instability score (LI), to quantify feature instability across and within datasets. Dividing PI by LI yields a ratio for how often a feature for a specific tissue class (e.g. low grade prostate cancer) is different between datasets from different sites versus what would be expected from random chance alone. Using this ratio we seek to quantify feature vulnerability to variations in slide preparation and digitization. Since our goal is to identify stable QH features we evaluate these features for their stability and thus inclusion in machine learning based classifiers in a use case involving prostate cancer. Specifically we examine QH features which may predict 5 year biochemical recurrence for prostate cancer patients who have undergone radical prostatectomy from digital slide images of surgically excised tissue specimens, 5 year biochemical recurrence being a strong predictor of disease recurrence. In this study we evaluated the ability of our feature robustness indices to identify the most stable and predictive features of 5 year biochemical recurrence using digitized slide images of surgically excised prostate cancer specimens from 80 different patients across 4 different sites. A total of 242 features from 5 different feature families were investigated to identify the most stable QH features from our set. Our feature robustness indices (PI and LI) suggested that five feature families (graph, shape, co-occurring gland tensors, gland sub-graphs, texture) were susceptible to variations in slide preparation and digitization across various sites. The family least affected was shape features in which 19.3% of features varied across laboratories while the most vulnerable family, at 55.6%, was the gland disorder features. However the disorder features were the most stable within datasets being different between random halves of a dataset in an average of just 4.1% of comparisons while texture features were the most unstable being different at a rate of 4.7%. We also compared feature stability across two datasets before and after color normalization. Color normalization decreased feature stability with 8% and 34% of features different between the two datasets in two outcome groups prior to normalization and 49% and 51% different afterwards. Our results appear to suggest that evaluation of QH features across multiple sites needs to be undertaken to assess robustness and class discriminability alone should not represent the benchmark for selection of QH features to build diagnostic and prognostic digital pathology classifiers.

[18F]fluoroethylcholine-PET/CT imaging for radiation treatment planning of recurrent and primary prostate cancer with dose escalation to PET/CT-positive lymph nodes.

PubMed

Würschmidt, Florian; Petersen, Cordula; Wahl, Andreas; Dahle, Jörg; Kretschmer, Matthias

2011-05-01

At present there is no consensus on irradiation treatment volumes for intermediate to high-risk primary cancers or recurrent disease. Conventional imaging modalities, such as CT, MRI and transrectal ultrasound, are considered suboptimal for treatment decisions. Choline-PET/CT might be considered as the imaging modality in radiooncology to select and delineate clinical target volumes extending the prostate gland or prostate fossa. In conjunction with intensity modulated radiotherapy (IMRT) and imaged guided radiotherapy (IGRT), it might offer the opportunity of dose escalation to selected sites while avoiding unnecessary irradiation of healthy tissues. Twenty-six patients with primary (n = 7) or recurrent (n = 19) prostate cancer received Choline-PET/CT planned 3D conformal or intensity modulated radiotherapy. The median age of the patients was 65 yrs (range 45 to 78 yrs). PET/CT-scans with F18-fluoroethylcholine (FEC) were performed on a combined PET/CT-scanner equipped for radiation therapy planning. The majority of patients had intermediate to high risk prostate cancer. All patients received 3D conformal or intensity modulated and imaged guided radiotherapy with megavoltage cone beam CT. The median dose to primary tumours was 75.6 Gy and to FEC-positive recurrent lymph nodal sites 66,6 Gy. The median follow-up time was 28.8 months. The mean SUV(max) in primary cancer was 5,97 in the prostate gland and 3,2 in pelvic lymph nodes. Patients with recurrent cancer had a mean SUV(max) of 4,38. Two patients had negative PET/CT scans. At 28 months the overall survival rate is 94%. Biochemical relapse free survival is 83% for primary cancer and 49% for recurrent tumours. Distant disease free survival is 100% and 75% for primary and recurrent cancer, respectively. Acute normal tissue toxicity was mild in 85% and moderate (grade 2) in 15%. No or mild late side effects were observed in the majority of patients (84%). One patient had a severe bladder shrinkage (grade 4) after a previous treatment with TUR of the prostate and seed implantation. FEC-PET/CT planning could be helpful in dose escalation to lymph nodal sites of prostate cancer.

Primary Gleason Grade 4 Impact on Biochemical Recurrence After Permanent Interstitial Brachytherapy in Japanese Patients With Low- or Intermediate-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uesugi, Tatsuya; Saika, Takashi, E-mail: saika@cc.okayama-u.ac.jp; Edamura, Kohei

2012-02-01

Purpose: To reveal a predictive factor for biochemical recurrence (BCR) after permanent prostate brachytherapy (PPB) using iodine-125 seed implantation in patients with localized prostate cancer classified as low or intermediate risk based on National Comprehensive Cancer Network (NCCN) guidelines. Methods and Materials: From January 2004 to December 2009, 414 consecutive Japanese patients with clinically localized prostate cancer classified as low or intermediate risk based on the NCCN guidelines were treated with PPB. The clinical factors including pathological data reviewed by a central pathologist and follow-up data were prospectively collected. Kaplan-Meier and Cox regression analyses were used to assess the factorsmore » associated with BCR. Results: Median follow-up was 36.5 months. The 2-, 3-, 4-, and 5-year BCR-free rates using the Phoenix definition were 98.3%, 96.0%, 91.6%, and 87.0%, respectively. On univariate analysis, the Gleason score, especially primary Gleason grade 4 in biopsy specimens, was a strong predicting factor (p < 0.0001), while age, initial prostate-specific antigen (PSA) level, T stage, and minimal dose delivered to 90% of the prostate volume (D90) were insignificant. Multivariate analysis indicated that a primary Gleason grade 4 was the most powerful prognostic factor associated with BCR (hazard ratio = 6.576, 95% confidence interval, 2.597-16.468, p < 0.0001). Conclusions: A primary Gleason grade 4 carried a worse BCR prognosis than the primary grade 3 in patients treated with PPB. Therefore, the indication for PPB in patients with a Gleason sum of 4 + 3 deserves careful and thoughtful consideration.« less

Early PET imaging with [68]Ga-PSMA-11 increases the detection rate of local recurrence in prostate cancer patients with biochemical recurrence.

PubMed

Uprimny, Christian; Kroiss, Alexander Stephan; Fritz, Josef; Decristoforo, Clemens; Kendler, Dorota; von Guggenberg, Elisabeth; Nilica, Bernhard; Maffey-Steffan, Johanna; di Santo, Gianpaolo; Bektic, Jasmin; Horninger, Wolfgang; Virgolini, Irene Johanna

2017-09-01

PET/CT using 68 Ga-labelled prostate-specific membrane antigen PSMA-11 (HBEDD-CC) has emerged as a promising imaging method in the diagnostic evaluation of prostate cancer (PC) patients with biochemical recurrence. However, assessment of local recurrence (LR) may be limited by intense physiologic tracer accumulation in the urinary bladder on whole-body scans, normally conducted 60 min post-tracer injection (p.i.). It could be shown on early dynamic imaging studies that 68 Ga-PSMA-11 uptake in PC lesions occurs earlier than tracer accumulation in the urinary bladder. This study aims to investigate whether early static PET acquisition increases detection rate of local recurrence on 68 Ga-PSMA-11 PET/CT in comparison to PET imaging 60 min p.i.. 203 consecutive PC patients with biochemical failure referred to 68 Ga-PSMA-11 PET/CT were analysed retrospectively (median prostate specific antigen (PSA) value: 1.44 ng/ml). In addition to whole-body PET/CT scans 60 min p.i., early static imaging of the pelvis was performed, starting at a median time of 283 s p.i. (range: 243-491 s). Assessment was based on visual analysis and calculation of maximum standardized uptake value (SUV max ) of pathologic lesions present in the pelvic area found on early PET imaging and on 60 min-PET scans. 26 patients (12.8%) were judged positive for LR on PET scans 60 min p.i. (median SUV max : 10.8; range: 4.7-40.9), whereas 50 patients (24.6%) revealed a lesion suggestive of LR on early PET imaging (median SUV max : 5.9; range: 2.9-17.6), resulting in a significant rise in detection rate (p < 0.001). Equivocal findings on PET scans 60 min p.i. decreased significantly with the help of early imaging (15.8% vs. 4.5% of patients; p < 0.001). Tracer activity in the urinary bladder with a median SUV max of 8.2 was present in 63 patients on early PET scans (31.0%). However, acquisition starting time of early PET scans differed significantly in the patient groups with and without urinary bladder activity (median starting time of 321 vs. 275 s p.i.; range: 281-491 vs. 243-311 s p.i.; p < 0.001). Median SUV max value of lesions suggestive of LR on early images was significantly higher in comparison to gluteal muscle, inguinal vessels and seminal vesicle/anastomosis (median SUV max : 5.9 vs. 1.9, 4.0 and 2.4, respectively). Performance of early imaging in 68 Ga-PSMA-11 PET/CT in addition to whole-body scans 60 min p.i. increases the detection rate of local recurrence in PC patients with biochemical recurrence. Acquisition of early PET images should be started as early as 5 min p.i. in order to avoid disturbing tracer activity in the urinary bladder occuring at a later time point.

Oncological Outcomes After Radical Prostatectomy for High-Risk Prostate Cancer Based on New Gleason Grouping System: A Validation Study From University of Southern California With 3,755 Cases.

PubMed

Djaladat, Hooman; Amini, Erfan; Xu, Weichen; Cai, Jie; Daneshmand, Siamak; Lieskovsky, Gary

2017-05-01

To assess the prognostic value of new Gleason grade grouping system in high-risk prostate cancer patients, we compared oncological outcomes after radical prostatectomy for patients with Gleason score 8 versus 9-10. Between 1987 and 2008, 3,755 men underwent radical prostatectomy with curative intent at University of Southern California. Patients who had Gleason score 8-10 at final histopathological evaluation (pT2-4N0) were included in this study. Eligible patients were divided into two groups; 226 with Gleason score 8 and 132 with Gleason score 9-10. Various patient and disease characteristics as well as oncological outcomes (biochemical recurrence, clinical recurrence, and overall survival) were compared between the groups. Impact of Gleason score on outcomes was controlled for preoperative prostate specific antigen, pathological stage, use of adjuvant radiotherapy, and neoadjuvant/adjuvant hormone therapy in multivariable analyses. A total of 358 patients (mean age: 65 years) were included in the analysis. Mean age and median duration of follow-up (9.6 years) were comparable between the study groups. Gleason 9-10 prostate cancer was associated with worse biochemical (HR 1.6; 95%CI [1.1-2.3]) and clinical recurrence free survival (HR = 1.9; 95%CI [1.1-3.3]); however, overall survival did not differ significantly between the groups. In addition, more patients with Gleason score 9-10 received adjuvant hormone therapy in the course of disease. Long-term follow-up after radical prostatectomy revealed significant differences in disease-specific outcomes between patients with Gleason score 8 versus 9-10. This sub-classification of high-risk patients might be helpful for patient counseling and determining therapeutic strategies. Prostate 77:743-748, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Incidental prostate cancer in patients with muscle-invasive bladder cancer who underwent radical cystoprostatectomy.

PubMed

Tanaka, Toshikazu; Koie, Takuya; Ohyama, Chikara; Hashimoto, Yasuhiro; Imai, Atsushi; Tobisawa, Yuki; Hatakeyama, Shingo; Yamamoto, Hayato; Yoneyama, Tohru; Horiguchi, Hirotaka; Kodama, Hirotake; Yoneyama, Takahiro

2017-11-01

The aim of this study was to analyze the features of incidentally detected prostate cancer (PCa) in radical cystoprostatectomy (RCP) specimens to determine their pathological characteristics and clinical significance. In this retrospective study, we reviewed the clinical and pathological records of 431 consecutive patients with muscle-invasive bladder cancer who underwent RCP at Hirosaki University. Of these, we focused on 237 male patients with prostate-specific antigen (PSA) measurements and digital rectal examinations (DRE) that were recorded prior to the RCP. Significant PCa was defined as a tumor with a Gleason 4 or 5 pattern, pathological T3 or higher stage, lymph node involvement or three or more multifocal lesions within the prostate specimen. We compared clinically significant and insignificant PCa. In this study, a total of 43 patients (18.1%) were diagnosed with incidental PCa via RCP specimens. Age, preoperative PSA levels and pathological T stage in patients with clinically significant PCa were considerably higher than in those with insignificant cancer. Apical involvement was found in 16 patients, including 11 of those with clinically significant PCa. By the end of the follow-up period, none of the enrolled patients had a biochemical recurrence after surgery or died from PCa. According to our findings, preoperative risk factors were not reliable enough to accurately predict clinically significant PCa. Although there was no biochemical relapse or clinical recurrence of PCa in this study, the potential oncologic risk of prostate-sparing RCP must be considered. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Diagnostic performance of a streamlined 18F-choline PET-CT protocol for the detection of prostate carcinoma recurrence in combination with appropriate-use criteria.

PubMed

Frood, R; Baren, J; McDermott, G; Bottomley, D; Patel, C; Scarsbrook, A

2018-04-30

To evaluate the efficacy of single time-point half-body (skull base to thighs) fluorine-18 choline positron emission tomography-computed tomography (PET-CT) compared to a triple-phase acquisition protocol in the detection of prostate carcinoma recurrence. Consecutive choline PET-CT studies performed at a single tertiary referral centre in patients with biochemical recurrence of prostate carcinoma between September 2012 and March 2017 were reviewed retrospectively. The indication for the study, imaging protocol used, imaging findings, whether management was influenced by the PET-CT, and subsequent patient outcome were recorded. Ninety-one examinations were performed during the study period; 42 were carried out using a triple-phase protocol (dynamic pelvic imaging for 20 minutes after tracer injection, half-body acquisition at 60 minutes and delayed pelvic scan at 90 minutes) between 2012 and August 2015. Subsequently following interim review of diagnostic performance, a streamlined protocol and appropriate-use criteria were introduced. Forty-nine examinations were carried out using the single-phase protocol between 2015 and 2017. Twenty-nine (69%) of the triple-phase studies were positive for recurrence compared to 38 (78%) of the single-phase studies. Only one patient who had a single-phase study would have benefited from a dynamic acquisition, they have required no further treatment or imaging and are currently under prostate-specific antigen (PSA) surveillance. Choline PET-CT remains a useful tool for the detection of prostate recurrence when used in combination with appropriate-use criteria. Removal of dynamic and delayed acquisition phases reduces study time without adversely affecting accuracy. Benefits include shorter imaging time which improves patient comfort, reduced cost, and improved scanner efficiency. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

A phase II trial of imatinib mesylate in patients with biochemical relapse of prostate cancer after definitive local therapy.

PubMed

Lin, Amy M; Rini, Brian I; Weinberg, Vivian; Fong, Kristen; Ryan, Charles J; Rosenberg, Jonathan E; Fong, Lawrence; Small, Eric J

2006-10-01

To determine the biological effects of imatinib mesylate (STI-571, Gleevec; Novartis Pharmaceuticals, Inc., East Hanover, NJ, USA), as measured by prostate-specific antigen (PSA) kinetics in men with biochemical relapse of prostate cancer after definitive local therapy. Men with prostate cancer, who had had definitive local therapy, with nonmetastatic recurrent disease as manifested by a rising PSA level, were enrolled on this phase II trial. Men received 400 mg of imatinib mesylate orally twice daily and continuously until disease progression or unacceptable toxicity. The PSA level was measured monthly. In all, 20 men with biochemically relapsed prostate cancer were treated. The median pretreatment PSA level was 5.4 ng/mL. Of the 19 evaluable men, one achieved a >or= 50% reduction in PSA level and two had decreases of <50%. For the 16 men in whom the on-treatment PSA doubling time (PSADT) could be calculated (those with increasing PSA level) the median PSADT did not increase significantly (5.8 vs 7.2 months, P = 0.64). Eleven of 20 men discontinued therapy due to toxicity and the trial was stopped early due to toxicity. Based on the lack of PSA modulation and pronounced toxicities leading to early closure of this trial, further study of single-agent imatinib mesylate at this dose (400 mg twice daily) cannot be recommended in this patient population.

How Precisely Can Prostate Cancer Be Managed?

PubMed Central

2016-01-01

Progress has been made in applying genetic information to disease management in the postgenomic era, and precision medicine is emerging in prostate cancer management. The prostate health index, the 4-kallikrein (4K) score, and the PCA3, TMPRSS2-ERG, and Prostarix tests have potential for refining prostate cancer screening in conjunction with traditional prostate-specific antigen testing. The Confirm MDx and PCA3 tests have shown promise in identifying men who need be rebiopsied after a primary negative biopsy. Oncotype DX, Prolaris, the biopsy-based Decipher prostate cancer test, and ProMark may improve predictive risk stratification in addition to the traditional Gleason score and tumor stage. Decipher and Prolaris may predict biochemical recurrence and metastasis after radical prostatectomy and possibly help identify patients who need adjuvant therapy. Androgen receptor splice variant 7 appears effective in guiding the selection of second hormonal manipulation with abiraterone or enzalutamide versus chemotherapy when treating metastatic castration-resistant prostate cancer. PMID:27915475

Clinical results of radical prostatectomy for patients with prostate cancer in Macau.

PubMed

Ho, Son-fat; Lao, Hio-fai; Li, Kin; Tse, Men-kin

2008-02-20

Incidence of prostate cancer has been increasing in recent decades. In the year 2005, prostate cancer became the second most common cancer in males in Macau. The purpose of this report was to review and summarize the clinical features and prognosis of the 54 patients undergoing radical prostatectomy in Macau Special Administrative Region (SAR), China. From November 2000 to November 2006, retropubic radical prostatectomy were performed in 54 cases for the treatment of prostate cancer. The mean age of patients was 69.8 years (range from 54 to 79). The preoperative prostate specific antigen (PSA) level, postoperative pathologic stage and Gleason's score, operation duration, intraoperative bleeding and intraoperative and postoperative complications were reported. The follow-up duration was 3 months to 6.25 years with a mean of 2.1 years. Postoperative parameters including PSA alteration, biochemical recurrence, local recurrence, distant metastasis and mortality were observed. Most of the patients in our study were diagnosed as localized prostate cancer. The patients' preoperative serum PSA was 0-4.0 ng/ml (16.7%), 4.0-10.0 ng/ml (51.8%), 10.1-20.0 ng/ml (24.1%) and above 20.0 ng/ml (7.4%). The TNM stage T1a+T1b comprised 7.6% of patients, stage T2a+T2b comprised 20.3%, stage T2c 38.9%, stage T3a 20.3% and over T3a only 12.9%. There were 9.5% cases with Gleason scores of 2-4, 41.5% with scores of 5-6, 30.2% with scores of 7 and 18.8% with scores of 8 - 10. The average operative duration was 216 minutes and the average intraoperative bleeding was 760 ml. Intraoperative complications included one massive hemorrhage (1.9%), one rectal injury (1.9%) and one obturator nerve injury (1.9%). Early postoperative complications consisted of urinary incontinence (14 cases, 25.9%), bladder neck stricture (5 cases, 9.3%), acute urinary retention (4 cases, 7.4%), pelvic effusion (2 cases, 3.8%), lymphocele (1 case, 1.9%) and vesicorectal fistula (only 1 case, 1.9%). For late postoperative complications, total incontinence or severe incontinence occurred in 6 cases (11.1%), urge incontinence in 2 cases (3.8%) and bladder neck contracture in 8 cases (14.8%). The total postoperative recurrence rate was 14.8%. Only 5 cases of biochemical recurrence were noted (9.3%). One case (1.9%) of local recurrence associated with elevated PSA was found. There were 2 cases of distant metastasis with elevated PSA (3.8%). Radical prostatectomy is a safe and effective method for the treatment of localized prostate cancer in Macau.

Clinical performance of 68Ga-PSMA-11 PET/MRI for the detection of recurrent prostate cancer following radical prostatectomy.

PubMed

Kranzbühler, Benedikt; Nagel, Hannes; Becker, Anton S; Müller, Julian; Huellner, Martin; Stolzmann, Paul; Muehlematter, Urs; Guckenberger, Matthias; Kaufmann, Philipp A; Eberli, Daniel; Burger, Irene A

2018-01-01

Sensitive visualization of recurrent prostate cancer foci is a challenge in patients with early biochemical recurrence (EBR). The recently established 68 Ga-PSMA-11 PET/CT has significantly improved the detection rate with published values of up to 55% for patients with a serum PSA concentration between 0.2-0.5 ng/mL. The increased soft tissue contrast in the pelvis using simultaneous 68 Ga-PSMA-11 PET/MRI might further improve the detection rate in patients with EBR and low PSA values over PET/CT. We retrospectively analyzed a cohort of 56 consecutive patients who underwent a 68 Ga-PSMA-11 PET/MRI for biochemical recurrence in our institution between April and December 2016 with three readers. Median PSA level was 0.99 ng/mL (interquartile range: 3.1 ng/mL). Detection of PSMA-positive lesions within the prostate fossa, local and distant lymph nodes, bones, or visceral organs was recorded. Agreement among observers was evaluated with Fleiss's kappa (k). Overall, in 44 of 56 patients (78.6%) PSMA-positive lesions were detected. In four of nine patients (44.4%) with a PSA < 0.2 ng/mL, suspicious lesions were detected (two pelvic and one paraaortic lymph nodes, and two bone metastases). In eight of 11 patients (72.7%) with a PSA between 0.2 and < 0.5 ng/mL, suspicious lesions were detected (two local recurrences, six lymph nodes, and one bone metastasis). Five out of 20 patients with a PSA < 0.5 ng/mL had extrapelvic disease. In 12 of 15 patients (80.0%) with a PSA between 0.5 and < 2.0 ng/mL, suspicious lesions were detected (four local recurrences, nine lymph nodes, and four bone metastases). In 20 of 21 patients (95.2%) with a PSA >2.0 ng/mL, suspicious lesions were detected. The overall interreader agreement for cancer detection was excellent (κ = 0.796, CI 0.645-0.947). Our data show that 68 Ga-PSMA-11 PET/MRI has a high detection rate for recurrent prostate cancer even at very low PSA levels <0.5 ng/mL. Furthermore, even at those low levels extrapelvic disease can be localized in 25% of the cases and local recurrence alone is seen only in 10%.

68Ga-PSMA-11 PET/CT: the rising star of nuclear medicine in prostate cancer imaging?

PubMed

Uprimny, Christian

2017-06-02

Ever since the introduction of 68 Ga-prostate-specific membrane antigen 11 positron-emission tomography/computed tomography ( 68 Ga-PSMA-11 PET/CT) a few years ago, it has rapidly achieved great success in the field of prostate cancer imaging. A large number of studies have been published to date, indicating a high potential of 68 Ga-PSMA-11 PET/CT in the work-up of prostate cancer patients, including primary diagnosis, staging and biochemical recurrence. The aim of this review is to present the most important data on this novel, highly promising imaging technique, and to formulate recommendations for possible applications of 68 Ga-PSMA-11 PET/CT in clinical routine.

Salvage radiotherapy after postprostatectomy biochemical failure: does pretreatment radioimmunoscintigraphy help select patients with locally confined disease?

PubMed

Liauw, Stanley L; Weichselbaum, Ralph R; Zagaja, Gregory P; Jani, Ashesh B

2008-08-01

Radioimmunoscintigraphy (RIS) has the potential to demonstrate early recurrences after prostatectomy and might be useful in selecting patients for salvage radiotherapy (RT). A total of 82 patients with adenocarcinoma of the prostate were treated with salvage RT between 1988 and 2005, for an elevated prostate-specific antigen (PSA) level after prostatectomy. Of the 82 patients, 32% had Gleason score 6 or less disease, 54% Gleason score 7 disease, 70% had Stage pT3 disease, 55% had positive margins, and 5% had pathologic lymph node involvement. The median pre-RT PSA level was 0.63 ng/mL. Of the 82 patients, 47 (57%) had a pre-RT RIS (ProstaScint) scan, which was used for both patient selection and target delineation. The RT regimen was a median dose of 66 Gy to the prostate bed. Also, 64% received androgen deprivation therapy. Biochemical failure was defined as a PSA level >0.1 ng/mL and increasing. Patients with a pre-RT RIS scan had a lower preoperative PSA level (p = 0.0240) and shorter follow-up (p = 0.0221) than those without RIS. With a median follow-up of 44 months, the biochemical control rate was 56% at 3 years and 48% at 5 years. Margin status was the only factor associated with biochemical control on univariate (p = 0.0055) and multivariate (p = 0.0044) analysis. Patients who had prostate bed-only uptake on RIS (n = 38) did not have improved outcomes, with biochemical control rates of 51% at 3 years and 40% at 5 years. Patients treated with salvage RT had modest responses. Patients who were selected for treatment with RIS did not have better biochemical outcomes. Our results indicated that patients with positive margins were most likely to benefit from salvage RT.

Adjuvant androgen-deprivation therapy following prostate total cryoablation in high-risk localized prostate cancer patients - Open-labeled randomized clinical trial.

PubMed

Chen, Chung-Hsin; Pu, Yeong-Shiau

2018-06-01

To investigate the efficacy and safety profile of 12-month adjuvant androgen-deprivation therapy (ADT) following total-gland cryoablation (TGC) in patients with high-risk localized prostate cancer (HRLPC). This open-label randomized trial included 38 HRLPC patients who received TGC between July 2011 and March 2013. Within 4 weeks after TGC, subjects were randomly assigned (1:1) to either the 12-month adjuvant ADT or non-adjuvant ADT group. The primary outcome was biochemical failure measured by the Phoenix definition. Adverse events were measured at month 1, 2, 3, 6, 9 and 12. In addition, a cohort of 145 HRLPC patients was selected retrospectively for outcome validation. The adjuvant ADT and non-adjuvant ADT groups did't differ in peri-operative characters, such as age, preoperative PSA, tumor stages, Gleason score, prostate size and cryoprobe number. Four patients with adjuvant ADT withdrew from this trial for personal reasons (N = 2), elevated liver function (N = 1) and poorly controlled hyperglycemia (N = 1). In contrast, none in non-adjuvant ADT group experienced adverse events. Biochemical failures were identified in 5 (26%) patients in each group during a median follow-up duration of 45 months. The median times to biochemical failure were 25 and 5.5 months for adjuvant ADT and non-adjuvant ADT groups, respectively. Biochemical-failure survival curves converged 24 months after TGC. Univariable and multivariable analyses revealed adjuvant ADT was not associated with biochemical recurrences in the validation cohort. Adjuvant ADT does not reduce biochemical failure for HRPLC patients undergoing TGC. It should be further confirmed by a larger cohort. Copyright © 2018. Published by Elsevier Inc.

Identification of miR-133b and RB1CC1 as independent predictors for biochemical recurrence and potential therapeutic targets for prostate cancer.

PubMed

Li, Xia; Wan, Xuechao; Chen, Hongbing; Yang, Shu; Liu, Yiyang; Mo, Wenjuan; Meng, Delong; Du, Wenting; Huang, Yan; Wu, Hai; Wang, Jingqiang; Li, Tao; Li, Yao

2014-05-01

We aimed to investigate the contribution of microRNA-133b (miR-133b) in prostate cancer cell proliferation, cell cycle, and apoptosis. We also examined expression of miR-133b in prostate cancer tissues, and evaluated the prognostic significance of miR-133b, as well as its target gene RB1CC1 in patients with prostate cancer after radical prostatectomy. miR-133b mimics (miR-133bm) and anti-miR-133b were transfected into LNCaP and PC-3 cells. CCK-8 was used to look at cell proliferation, flow cytometric analysis was carried out to study cell cycle, and apoptosis was determined by caspase-3 activity. miR-133b expression was assessed by real-time reverse transcription PCR and in situ hybridization in prostatic cell lines and 178 prostate tissue samples, respectively. The protein level of RB1CC1 was examined by Western blot and immunohistochemistry in prostatic cell lines and prostate tissue samples, respectively. Overexpression of miR-133b in LNCaP cells boosted cell proliferation and cell-cycle progression, but inhibited apoptosis; in contrast, miR-133bm promoted cell apoptosis, but suppressed cell proliferation and cell-cycle progression in PC-3 cells. In LNCaP cells, silencing of RB1CC1, a target of miR-133b, inhibited cell apoptosis, and promoted cell-cycle progression. Moreover, miR-133b expression was significantly inversely correlated with RB1CC1 expression in prostate cancer tissues. Multivariate Cox analysis indicated that miR-133b and RB1CC1 might be two independent prognostic factors of biochemical recurrence. miR-133b might enhance tumor-promoting properties in less aggressive LNCaP cells, whereas this miR may act as a tumor suppressor in more aggressive PC-3 cells. miR-133b and RB1CC1 were independent prognostic indicators for prostate cancer. ©2014 AACR.

Performance characteristics and relationship of PSA value/kinetics on carbon-11 acetate PET/CT imaging in biochemical relapse of prostate cancer.

PubMed

Almeida, Fabio D; Yen, Chi-Kwan; Scholz, Mark C; Lam, Richard Y; Turner, Jeffrey; Bans, Larry L; Lipson, Robert

2017-01-01

An elevated serum prostate-specific antigen (PSA) level alone cannot distinguish between local-regional recurrences and distant metastases after treatment with curative intent. With available salvage treatments, it has become important to localize the site of recurrence. 11 C-Acetate PET/CT was performed in patients with rising PSA, with statistical analysis of detection rates, sites/location of detection, PSA kinetics and comparison with other tracers (FDG and Choline). Correlation to biopsy, subsequent imaging and PSA response to focal treatment was also performed. 88% (637) of 721 11 C-Acetate PET/CT scans performed were positive. There was a statistically significant difference in PSA values between the positive and negative scans (P < 0.001 for mean difference) with the percentage of positive scans and PSA having a positive correlation. A PSA of 1.09 ng/mL was found to be an optimal cutoff. PSAdT was significantly correlated with a positive scan only when the PSA was < 1.0 ng/mL. For this subgroup, a PSAdT of < 3.8 months appeared significant (P < 0.05) as an optimal cutoff point. 11 C-Acetate PET/CT demonstrates a high detection rate for the site of recurrence/metastasis in biochemical relapsed prostate cancer (88% overall detection rate, PPV 90.8%). This analysis suggests an optimal PSA threshold of > 1.09 ng/mL or a PSAdT of < 3.8 months when the PSA is below 1.0 ng/mL as independent predictors of positive findings.

Novel technology of molecular radio-guidance for lymph node dissection in recurrent prostate cancer by PSMA-ligands.

PubMed

Rauscher, Isabel; Horn, Thomas; Eiber, Matthias; Gschwend, Jürgen E; Maurer, Tobias

2018-04-01

Recently, prostate-specific membrane antigen-radioguided surgery (PSMA-RGS) has been introduced as a promising new and individual treatment concept in patients with localised recurrent prostate cancer (PC). In the following, we want to review our experience with PSMA-RGS in patients with localised biochemical recurrent PC. A non-systematic review of the literature was carried out with focus on technical and logistical aspects of PSMA-RGS. Furthermore, published data on intraoperative detection of metastatic lesions compared to preoperative PSMA-PET and postoperative histopathology, postoperative complications as well as oncological follow-up data are summarized. Finally, relevant aspects on prerequisites for PSMA-RGS, patient selection, and the potential benefit of additional salvage radiotherapy or potential future applications of robotic PSMA-RGS with drop-in γ-probes are discussed. First results show that PSMA-RGS is very sensitive and specific in tracking suspicious lesions intraoperatively. Prerequisite for patient selection and localisation of tumour recurrence is a positive Ga-HBED-CC PSMA positron-emission tomography (PET) scan with preferably only singular soft tissue or lymph node recurrence after primary treatment. Furthermore, PSMA-RGS has the potential to positively influence oncological outcome. PSMA-RGS seems to be of high value in patients with localised PC recurrence for exact localisation and resection of oftentimes small metastatic lesions using intraoperative and ex vivo γ-probe measurements. However, patient identification on the basis of Ga-HBED-CC-PSMA PET imaging as well as clinical parameters is crucial to obtain satisfactory results.

Size-adjusted Quantitative Gleason Score as a Predictor of Biochemical Recurrence after Radical Prostatectomy.

PubMed

Deng, Fang-Ming; Donin, Nicholas M; Pe Benito, Ruth; Melamed, Jonathan; Le Nobin, Julien; Zhou, Ming; Ma, Sisi; Wang, Jinhua; Lepor, Herbert

2016-08-01

The risk of biochemical recurrence (BCR) following radical prostatectomy for pathologic Gleason 7 prostate cancer varies according to the proportion of Gleason 4 component. We sought to explore the value of several novel quantitative metrics of Gleason 4 disease for the prediction of BCR in men with Gleason 7 disease. We analyzed a cohort of 2630 radical prostatectomy cases from 1990-2007. All pathologic Gleason 7 cases were identified and assessed for quantity of Gleason pattern 4. Three methods were used to quantify the extent of Gleason 4: a quantitative Gleason score (qGS) based on the proportion of tumor composed of Gleason pattern 4, a size-weighted score (swGS) incorporating the overall quantity of Gleason 4, and a size index (siGS) incorporating the quantity of Gleason 4 based on the index lesion. Associations between the above metrics and BCR were evaluated using Cox proportional hazards regression analysis. qGS, swGS, and siGS were significantly associated with BCR on multivariate analysis when adjusted for traditional Gleason score, age, prostate specific antigen, surgical margin, and stage. Using Harrell's c-index to compare the scoring systems, qGS (0.83), swGS (0.84), and siGS (0.84) all performed better than the traditional Gleason score (0.82). Quantitative measures of Gleason pattern 4 predict BCR better than the traditional Gleason score. In men with Gleason 7 prostate cancer, quantitative analysis of the proportion of Gleason pattern 4 (quantitative Gleason score), as well as size-weighted measurement of Gleason 4 (size-weighted Gleason score), and a size-weighted measurement of Gleason 4 based on the largest tumor nodule significantly improve the predicted risk of biochemical recurrence compared with the traditional Gleason score. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Vegetable and fruit intake after diagnosis and risk of prostate cancer progression.

PubMed

Richman, Erin L; Carroll, Peter R; Chan, June M

2012-07-01

Cruciferous vegetables, tomato sauce and legumes have been associated with reduced risk of incident advanced prostate cancer. In vitro and animal studies suggest these foods may inhibit progression of prostate cancer, but there are limited data in men. Therefore, we prospectively examined whether intake of total vegetables, and specifically cruciferous vegetables, tomato sauce and legumes, after diagnosis reduce risk of prostate cancer progression among 1,560 men diagnosed with non-metastatic prostate cancer and participating in the Cancer of the Prostate Strategic Urologic Research Endeavor, a United States prostate cancer registry. As a secondary analysis, we also examined other vegetable subgroups, total fruit and subgroups of fruits. The participants were diagnosed primarily at community-based clinics and followed from 2004 to 2009. We assessed vegetable and fruit intake via a semi-quantitative food frequency questionnaire, and ascertained prostate cancer outcomes via urologist report and medical records. We observed 134 events of progression (53 biochemical recurrences, 71 secondary treatments likely due to recurrence, 6 bone metastases and 4 prostate cancer deaths) during 3,171 person-years. Men in the fourth quartile of post-diagnostic cruciferous vegetable intake had a statistically significant 59% decreased risk of prostate cancer progression compared to men in the lowest quartile (hazard ratio (HR): 0.41; 95% confidence interval (CI): 0.22, 0.76; p-trend: 0.003). No other vegetable or fruit group was statistically significantly associated with risk of prostate cancer progression. In conclusion, cruciferous vegetable intake after diagnosis may reduce risk of prostate cancer progression. Copyright © 2011 UICC.

Advances in prostate-specific membrane antigen PET of prostate cancer.

PubMed

Bouchelouche, Kirsten; Choyke, Peter L

2018-05-01

In recent years, a large number of reports have been published on prostate-specific membrane antigen (PSMA)/PET in prostate cancer (PCa). This review highlights advances in PSMA PET in PCa during the past year. PSMA PET/computed tomography (CT) is useful in detection of biochemical recurrence, especially at low prostate-specific antigen (PSA) values. The detection rate of PSMA PET is influenced by PSA level. For primary PCa, PSMA PET/CT shows promise for tumour localization in the prostate, especially in combination with multiparametric MRI (mpMRI). For primary staging, PSMA PET/CT can be used in intermediate and high-risk PCa. Intraoperative PSMA radioligand guidance seems promising for detection of malignant lymph nodes. While the use of PSMA PET/MRI in primary localized disease is limited to high and intermediate-risk patients and localized staging, in the recurrence setting, PET/MRI can be particularly helpful when the lesions are subtle. PSMA PET/CT is superior to choline PET/CT and other conventional imaging modalities. Molecular imaging with PSMA PET continues to pave the way for personalized medicine in PCa.However, large prospective clinical studies are still needed to fully evaluate the role of PSMA PET/CT and PET/MRI in the clinical workflow of PCa.

[Prostate biopsy under magnetic resonance imaging guidance].

PubMed

Kuplevatskiy, V I; CherkashiN, M A; Roshchin, D A; Berezina, N A; Vorob'ev, N A

2016-01-01

Prostate cancer (PC) is one of the most important problems in modern oncology. According to statistical data, PC ranks second in the cancer morbidity structure in the Russian Federation and developed countries and its prevalence has been progressively increasing over the past decade. A need for early diagnosis and maximally accurate morphological verification of the diagnosis in difficult clinical cases (inconvenient tumor location for standard transrectal biopsy; gland scarring changes concurrent with prostatitis and hemorrhage; threshold values of prostate-specific antigen with unclear changes in its doubling per unit time; suspicion of biochemical recurrence or clinical tumor progression after special treatment) leads to revised diagnostic algorithms and clinically introduced new high-tech invasive diagnostic methods. This paper gives the first analysis of literature data on Russian practice using one of the new methods to verify prostate cancer (transrectal prostate cancer under magnetic resonance imaging (MRI) guidance). The have sought the 1995-2015 data in the MEDLINE and Pubmed.

Salvage of locally recurrent prostate cancer after definitive radiotherapy.

PubMed

Mendenhall, William M; Henderson, Randal H; Hoppe, Bradford S; Nichols, Romaine C; Mendenhall, Nancy P

2014-08-01

Although a significant proportion of patients with localized prostate cancer are cured after definitive radiotherapy, solitary local recurrence is observed in a subset of patients and poses a management challenge. Curative-intent treatment options include prostatectomy, reirradiation, cryotherapy, and high-intensity-focused ultrasound. Outcomes data after any of these options are relatively limited. The 5-year biochemical progression-free survival rate is approximately 50% after salvage prostatectomy. However, the morbidity rate of the procedure is significantly higher compared with that observed in previously untreated patients. The likelihood of cure after low dose rate brachytherapy is similar to that observed after salvage prostatectomy, and the morbidity, although significant is less. Although cryotherapy and high-intensity-focused ultrasound may be less morbid than a prostatectomy, the probability of cure is probably lower.

Reader Training for the Restaging of Biochemically Recurrent Prostate Cancer Using 18F-Fluciclovine PET/CT.

PubMed

Miller, Matthew P; Kostakoglu, Lale; Pryma, Daniel; Yu, Jian Qin; Chau, Albert; Perlman, Eric; Clarke, Bonnie; Rosen, Donald; Ward, Penelope

2017-10-01

18 F-Fluciclovine is a novel PET/CT tracer. This blinded image evaluation (BIE) sought to demonstrate that, after limited training, readers naïve to 18 F-fluciclovine could interpret 18 F-fluciclovine images from subjects with biochemically recurrent prostate cancer with acceptable diagnostic performance and reproducibility. The primary objectives were to establish individual readers' diagnostic performance and the overall interpretation (2/3 reader concordance) compared with standard-of-truth data (histopathology or clinical follow-up) and to evaluate interreader reproducibility. Secondary objectives included comparison to the expert reader and assessment of intrareader reproducibility. Methods: 18 F-Fluciclovine PET/CT images ( n = 121) and corresponding standard-of-truth data were collected from 110 subjects at Emory University using a single-time-point static acquisition starting 5 min after injection of approximately 370 MBq of 18 F-fluciclovine. Three readers were trained using standardized interpretation methodology and subsequently evaluated the images in a blinded manner. Analyses were conducted at the lesion, region (prostate, including bed and seminal vesicle, or extraprostatic, including all lymph nodes, bone, or soft-tissue metastasis), and subject level. Results: Lesion-level overall positive predictive value was 70.5%. The readers' positive predictive value and negative predictive value were broadly consistent with each other and with the onsite read. Sensitivity was highest for readers 1 and 2 (68.5% and 63.9%, respectively) whereas specificity was highest for reader 3 (83.6%). Overall, prostate-level sensitivity was high (91.4%), but specificity was moderate (48.7%). Interreader agreement was 94.7%, 74.4%, and 70.3% for the lesion, prostate, and extraprostatic levels, respectively, with associated Fleiss' κ-values of 0.54, 0.50, and 0.57. Intrareader agreement was 97.8%, 96.9%, and 99.1% at the lesion level; 100%, 100%, and 91.7% in the prostate region; and 83.3%, 75.0%, and 83.3% in the extraprostatic region for readers 1, 2, and 3, respectively. Concordance between the BIE and the onsite reader exceeded 75% for each reader at the lesion, region, and subject levels. Conclusion: Specific training in the use of standardized interpretation methodology for assessment of 18 F-fluciclovine PET/CT images enables naïve readers to achieve acceptable diagnostic performance and reproducibility when staging recurrent prostate cancer. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Metabolic syndrome, endocrine disruptors and prostate cancer associations: biochemical and pathophysiological evidences

PubMed Central

Quagliariello, Vincenzo; Rossetti, Sabrina; Cavaliere, Carla; Di Palo, Rossella; Lamantia, Elvira; Castaldo, Luigi; Nocerino, Flavia; Ametrano, Gianluca; Cappuccio, Francesca; Malzone, Gabriella; Montanari, Micaela; Vanacore, Daniela; Romano, Francesco Jacopo; Piscitelli, Raffaele; Iovane, Gelsomina; Pepe, Maria Filomena; Berretta, Massimiliano; D'Aniello, Carmine; Perdonà, Sisto; Muto, Paolo; Botti, Gerardo; Ciliberto, Gennaro; Veneziani, Bianca Maria; De Falco, Francesco; Maiolino, Piera; Caraglia, Michele; Montella, Maurizio; Iaffaioli, Rosario Vincenzo; Facchini, Gaetano

2017-01-01

This review summarizes the main pathophysiological basis of the relationship between metabolic syndrome, endocrine disruptor exposure and prostate cancer that is the most common cancer among men in industrialized countries. Metabolic syndrome is a cluster of metabolic and hormonal factors having a central role in the initiation and recurrence of many western chronic diseases including hormonal-related cancers and it is considered as the worlds leading health problem in the coming years. Many biological factors correlate metabolic syndrome to prostate cancer and this review is aimed to focus, principally, on growth factors, cytokines, adipokines, central obesity, endocrine abnormalities and exposure to specific endocrine disruptors, a cluster of chemicals, to which we are daily exposed, with a hormone-like structure influencing oncogenes, tumor suppressors and proteins with a key role in metabolism, cell survival and chemo-resistance of prostate cancer cells. Finally, this review will analyze, from a molecular point of view, how specific foods could reduce the relative risk of incidence and recurrence of prostate cancer or inhibit the biological effects of endocrine disruptors on prostate cancer cells. On the basis of these considerations, prostate cancer remains a great health problem in terms of incidence and prevalence and interventional studies based on the treatment of metabolic syndrome in cancer patients, minimizing exposure to endocrine disruptors, could be a key point in the overall management of this disease. PMID:28389628

Metabolic syndrome, endocrine disruptors and prostate cancer associations: biochemical and pathophysiological evidences.

PubMed

Quagliariello, Vincenzo; Rossetti, Sabrina; Cavaliere, Carla; Di Palo, Rossella; Lamantia, Elvira; Castaldo, Luigi; Nocerino, Flavia; Ametrano, Gianluca; Cappuccio, Francesca; Malzone, Gabriella; Montanari, Micaela; Vanacore, Daniela; Romano, Francesco Jacopo; Piscitelli, Raffaele; Iovane, Gelsomina; Pepe, Maria Filomena; Berretta, Massimiliano; D'Aniello, Carmine; Perdonà, Sisto; Muto, Paolo; Botti, Gerardo; Ciliberto, Gennaro; Veneziani, Bianca Maria; De Falco, Francesco; Maiolino, Piera; Caraglia, Michele; Montella, Maurizio; Iaffaioli, Rosario Vincenzo; Facchini, Gaetano

2017-05-02

This review summarizes the main pathophysiological basis of the relationship between metabolic syndrome, endocrine disruptor exposure and prostate cancer that is the most common cancer among men in industrialized countries. Metabolic syndrome is a cluster of metabolic and hormonal factors having a central role in the initiation and recurrence of many western chronic diseases including hormonal-related cancers and it is considered as the world's leading health problem in the coming years. Many biological factors correlate metabolic syndrome to prostate cancer and this review is aimed to focus, principally, on growth factors, cytokines, adipokines, central obesity, endocrine abnormalities and exposure to specific endocrine disruptors, a cluster of chemicals, to which we are daily exposed, with a hormone-like structure influencing oncogenes, tumor suppressors and proteins with a key role in metabolism, cell survival and chemo-resistance of prostate cancer cells. Finally, this review will analyze, from a molecular point of view, how specific foods could reduce the relative risk of incidence and recurrence of prostate cancer or inhibit the biological effects of endocrine disruptors on prostate cancer cells. On the basis of these considerations, prostate cancer remains a great health problem in terms of incidence and prevalence and interventional studies based on the treatment of metabolic syndrome in cancer patients, minimizing exposure to endocrine disruptors, could be a key point in the overall management of this disease.

Phase I/II prospective trial of cancer-specific imaging using ultrasound spectrum analysis tissue-type imaging to guide dose-painting prostate brachytherapy.

PubMed

Ennis, Ronald D; Quinn, S Aidan; Trichter, Frieda; Ryemon, Shannon; Jain, Anudh; Saigal, Kunal; Chandrashekhar, Sarayu; Romas, Nicholas A; Feleppa, Ernest J

2015-01-01

To assess the technical feasibility, toxicity, dosimetry, and preliminary efficacy of dose-painting brachytherapy guided by ultrasound spectrum analysis tissue-type imaging (TTI) in low-risk, localized prostate cancer. Fourteen men with prostate cancer who were candidates for brachytherapy as sole treatment were prospectively enrolled. Treatment planning goal was to escalate the tumor dose to 200% with a modest de-escalation of dose to remaining prostate compared with our standard. Primary end points included technical feasibility of TTI-guided brachytherapy and equivalent or better toxicity compared with standard brachytherapy. Secondary end points included dose escalation to tumor regions and de-escalated dose to nontumor regions on the preimplant plan, negative prostate biopsy at 2 years, and freedom from biochemical failure. Thirteen of fourteen men successfully completed the TTI-guided brachytherapy procedure for a feasibility rate of 93%. A software malfunction resulted in switching one patient from TTI-guided to standard brachytherapy. An average of 2.7 foci per patient was demonstrated and treated with an escalated dose. Dosimetric goals on preplan were achieved. One patient expired from unrelated causes 65 days after brachytherapy. Toxicity was at least as low as standard brachytherapy. Two-year prostate biopsies were obtained from six men; five (83%) were definitively negative, one showed evidence of disease with treatment effect, and none were positive. No patients experienced biochemical recurrence after a median followup of 31.5 (24-52) months. We have demonstrated that TTI-guided dose-painting prostate brachytherapy is technically feasible and results in clinical outcomes that are encouraging in terms of low toxicity and successful biochemical disease control. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

High Occurrence of Aberrant Lymph Node Spread on Magnetic Resonance Lymphography in Prostate Cancer Patients With a Biochemical Recurrence After Radical Prostatectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meijer, Hanneke J.M., E-mail: H.Meijer@rther.umcn.nl; Lin, Emile N. van; Debats, Oscar A.

2012-03-15

Purpose: To investigate the pattern of lymph node spread in prostate cancer patients with a biochemical recurrence after radical prostatectomy, eligible for salvage radiotherapy; and to determine whether the clinical target volume (CTV) for elective pelvic irradiation in the primary setting can be applied in the salvage setting for patients with (a high risk of) lymph node metastases. Methods and Materials: The charts of 47 prostate cancer patients with PSA recurrence after prostatectomy who had positive lymph nodes on magnetic resonance lymphography (MRL) were reviewed. Positive lymph nodes were assigned to a lymph node region according to the guidelines ofmore » the Radiation Therapy Oncology Group (RTOG) for delineation of the CTV for pelvic irradiation (RTOG-CTV). We defined four lymph node regions for positive nodes outside this RTOG-CTV: the para-aortal, proximal common iliac, pararectal, and paravesical regions. They were referred to as aberrant lymph node regions. For each patient, clinical and pathologic features were recorded, and their association with aberrant lymph drainage was investigated. The distribution of positive lymph nodes was analyzed separately for patients with a prostate-specific antigen (PSA) <1.0 ng/mL. Results: MRL detected positive aberrant lymph nodes in 37 patients (79%). In 20 patients (43%) a positive lymph node was found in the pararectal region. Higher PSA at the time of MRL was associated with the presence of positive lymph nodes in the para-aortic region (2.49 vs. 0.82 ng/mL; p = 0.007) and in the proximal common iliac region (1.95 vs. 0.59 ng/mL; p = 0.009). There were 18 patients with a PSA <1.0 ng/mL. Ten of these patients (61%) had at least one aberrant positive lymph node. Conclusion: Seventy-nine percent of the PSA-recurrent patients had at least one aberrant positive lymph node. Application of the standard RTOG-CTV for pelvic irradiation in the salvage setting therefore seems to be inappropriate.« less

[Impact of Gleason score on biochemical recurrence free survival after radical prostatectomy with positive surgical margins].

PubMed

Roux, V; Eyraud, R; Brureau, L; Gourtaud, G; Senechal, C; Fofana, M; Blanchet, P

Research of predictive factors of biochemical recurrence to guide the establishment of an adjuvant treatment after radical prostatectomy for cancer with positive surgical margins. A retrospective cohort of 1577 afro-caribbean patients undergoing radical prostatectomy operated between 1st January 2000 and 1st July 2013 was analyzed. In this cohort, 406 patients had positive surgical margin, we excluded 11 patients who received adjuvant therapy (radiotherapy, hormonotherapy, radio-hormonotherapy) and 2 patients for whom histological analysis of the surgical specimen was for a pT4 pathological stage. After a descriptive analysis, we used a Cox model to look for predictors of survival without biochemical recurrence then, depending on the significant variables, we separated our population into six groups: stage pT2 with Gleason score≤3+4 (group 1), stage pT2 with a score of Gleason≥4+3 (group 2), stage pT3a with a Gleason core≤3+4 (group 3), pT3a stage with a score of Gleason≥4+3 (group 4), stage pT3b with a Gleason score≤3+4 (group 5) and stage pT3b Gleason≥with a score of 4+3 (group 6) and compared survival without biochemical recurrence using a log rank test. After radical prostatectomy with surgical margins with an anatomopathological stage≤pT3b, a Gleason score≥4+3 had a pejorative survival without biochemical recurrence than pathological stage (P<0.001). In multivariate analysis, predictors of survival without biochemical recurrence after radical prostatectomy with positive surgical margins were the majority Gleason postoperative (P<0.0001), pathological stage (P=0.049) adjusted preoperative PSA (P=0.826), with the body mass index (BMI) (P=0.59) and tumor volume (P=0.95). A high postoperatively Gleason score (≥4+3) has a better predictive value of biochemical recurrence than pathological stage pT2 or pT3 at the patients having been treated for prostate cancer by radical prostatectomy with positive surgical margins. 4. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Contribution of 11C-Choline PET/CT in prostate carcinoma biochemical relapse with serum PSA level below 1 ng/ml.

PubMed

Gómez-de la Fuente, F J; Martínez-Rodríguez, I; de Arcocha-Torres, M; Quirce, R; Jiménez-Bonilla, J; Martínez-Amador, N; Banzo, I

11 C-choline PET/CT has demonstrated good results in the restaging of prostate cancer (PCa) with high serum prostate specific antigen (PSA), but its use in patients with low serum PSA is controversial. Our aim was to evaluate the contribution of 11 C-choline PET/CT in patients with PCa, biochemical relapse and PSA <1 ng/ml. Fifty consecutive patients (mean age: 65.9±5.6 years) with biochemical relapse of PCa and serum PSA <1ng/ml were evaluated retrospectively. PET/CT was performed 20min after intravenous administration of 555-740 MBq of 11 C-choline. Minimum follow up time was 30 months. Twenty-one out of 50 patients (42%) had an abnormal 11 C-choline PET/CT. In 7 out of 21 patients (14%) tumor was confirmed (4 in prostatic bed, 4 in pelvic lymph nodes, 2 in mediastinal lymph nodes and one synchronous sigmoid carcinoma), and in all cases the initial therapeutic planning was modified. In 2 patients (4%) subsequent tests diagnosed a benign disease (one sarcoidosis, one tuberculosis sequelae) and in 3 patients (6%) they ruled out pathology. The other 9 patients (18%) had no further assessment (7 mediastinal and 4 pelvic lymph nodes). Twenty-nine out of 50 patients (58%) had a normal PET/CT. At 30 months, follow up recurrence was confirmed only in 2 of these patients. 11 C-choline PET/CT proved its usefulness in demonstrating tumor in 14% of patients with BR of PCa and serum PSA <1ng/ml, with therapeutic implications. In 4% of patients a benign condition was detected. A normal 11 C-choline PET/CT was associated with a very low rate of recurrence at 30 months. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Comparison of Biochemical Recurrence-Free Survival after Radical Prostatectomy Triggered by Grade Reclassification during Active Surveillance and in Men Newly Diagnosed with Similar Grade Disease.

PubMed

Diniz, Clarissa P; Landis, Patricia; Carter, H Ballentine; Epstein, Jonathan I; Mamawala, Mufaddal

2017-09-01

We compared biochemical recurrence between men on active surveillance who underwent radical prostatectomy triggered by grade reclassification and men diagnosed with similar grade disease treated with immediate radical prostatectomy. We retrospectively analyzed the records of men who underwent surgery from 1995 to 2015 at our institution. We identified 4 groups, including 94 and 56 men on active surveillance who underwent radical prostatectomy following reclassification to Gleason 7 (3 + 4) or greater (grade groups 2 or greater) and Gleason 7 (3 + 4) (grade group 2), and 3,504 and 1,979 in the immediate prostatectomy group diagnosed with grade group 2 or greater and 2, respectively. Biochemical recurrence was assessed by Kaplan-Meir analysis and a multivariable Cox model. Men on active surveillance had a lower incidence of biochemical recurrence than men in the immediate radical prostatectomy groups for biopsy grade groups 2 or greater and 2 (each p <0.05). One, 5 and 10-year biochemical recurrence-free survival for men in the active surveillance group vs the immediate radical prostatectomy group was 97.9% vs 85.5%, 76.6% vs 65.1% and 69.0% vs 54.2% in biopsy grade groups 2 or greater (p = 0.009) and 96.4% vs 91.2%, 89.6% vs 74.0% and 89.6% vs 63.9%, respectively, in biopsy grade group 2 (p = 0.071). For biopsy grade groups 2 or greater there was no significant difference in the risk of biochemical recurrence between the groups after adjusting for age, biopsy extent of cancer and prostate specific antigen density. Patients on active surveillance reclassified to grade groups 2 or greater are at no greater risk for treatment failure than men newly diagnosed with similar grades. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Stratified analysis of 800 Asian patients after robot-assisted radical prostatectomy with a median 64 months of follow up.

PubMed

Abdel Raheem, Ali; Kim, Dae Keun; Santok, Glen Denmer; Alabdulaali, Ibrahim; Chung, Byung Ha; Choi, Young Deuk; Rha, Koon Ho

2016-09-01

To report the 5-year oncological outcomes of robot-assisted radical prostatectomy from the largest series ever reported from Asia. A retrospective analysis of 800 Asian patients who were treated with robot-assisted radical prostatectomy from July 2005 to May 2010 in the Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea was carried out. The primary end-point was to evaluate the biochemical recurrence. The secondary end-point was to show the biochemical recurrence-free survival, metastasis-free survival and cancer-specific survival. A total of 197 (24.65%), 218 (27.3%), and 385 (48.1%) patients were classified as low-, intermediate- and high-risk patients according to the D'Amico risk stratification risk criteria, respectively. The median follow-up period was 64 months (interquartile range 28-71 months). The overall incidence of positive surgical margin was 36.6%. There was biochemical recurrence in 183 patients (22.9%), 38 patients (4.8%) developed distant metastasis and 24 patients (3%) died from prostate cancer. Actuarial biochemical recurrence-free survival, metastasis-free survival, and cancer-specific survival rates at 5 years were 76.4%, 94.6% and 96.7%, respectively. Positive lymph node was associated with lower 5-year biochemical recurrence-free survival (9.1%), cancer-specific survival (75.7%) and metastasis-free survival (61.9%) rates (P < 0.001). On multivariable analysis, among all the predictors, positive lymph node was the strongest predictor of biochemical recurrence, cancer-specific survival and metastasis-free survival (P < 0.001). Herein we report the largest robot-assisted radical prostatectomy series from Asia. Robot-assisted radical prostatectomy is confirmed to be an oncologically safe procedure that is able to provide effective 5-year cancer control, even in patients with high-risk disease. © 2016 The Japanese Urological Association.

Impact of 68Ga-PSMA-11 PET/CT on the Management of Prostate Cancer Patients with Biochemical Recurrence.

PubMed

Calais, Jeremie; Fendler, Wolfgang P; Eiber, Matthias; Gartmann, Jeannine; Chu, Fang-I; Nickols, Nicholas G; Reiter, Robert E; Rettig, Matthew B; Marks, Leonard S; Ahlering, Thomas E; Huynh, Linda M; Slavik, Roger; Gupta, Pawan; Quon, Andrew; Allen-Auerbach, Martin S; Czernin, Johannes; Herrmann, Ken

2018-03-01

In this prospective survey of referring physicians, we investigated whether and how 68 Ga-labeled prostate-specific membrane antigen 11 ( 68 Ga-PSMA-11) PET/CT affects the implemented management of prostate cancer patients with biochemical recurrence (BCR). Methods: We conducted a prospective survey of physicians (NCT02940262) who referred 161 patients with prostate cancer BCR (median prostate-specific antigen value, 1.7 ng/mL; range, 0.05-202 ng/mL). Referring physicians completed one questionnaire before the scan to indicate the treatment plan without 68 Ga-PSMA-11 PET/CT information (Q1; n = 101), one immediately after the scan to denote intended management changes (Q2; n = 101), and one 3-6 mo later to document the final implemented management (Q3; n = 56). The implemented management was also obtained via electronic chart review or patient contact ( n = 45). Results: A complete documented management strategy (Q1 + Q2 + implemented management) was available for 101 of 161 patients (63%). Seventy-six of these (75%) had a positive 68 Ga-PSMA-11 PET/CT result. The implemented management differed from the prescan intended management (Q1) in 54 of 101 patients (53%). The postscan intended management (Q2) differed from the prescan intended management (Q1) in 62 of 101 patients (61%); however, these intended changes were not implemented in 29 of 62 patients (47%). Pelvic nodal and extrapelvic metastatic disease on 68 Ga-PSMA-11 PET/CT (PSMA T0N1M0 and PSMA T0N1M1 patterns) was significantly associated with implemented management changes ( P = 0.001 and 0.05). Conclusion: Information from 68 Ga-PSMA-11 PET/CT brings about management changes in more than 50% of prostate cancer patients with BCR (54/101; 53%). However, intended management changes early after 68 Ga-PSMA-11 PET/CT frequently differ from implemented management changes. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

A Review of Pomegranate in Prostate Cancer

PubMed Central

Paller, Channing J.; Pantuck, Allan; Carducci, Michael A.

2017-01-01

Background Preclinical studies showing that pomegranate juice and its components inhibit prostate cancer led to multiple clinical trials to determine whether pomegranate products could slow the growth of prostate cancer. This review summarizes the preclinical data and discusses the results of the clinical trials. Methods Trials targeted patients on active surveillance, neoadjuvant patients, patients with biochemical recurrence (BCR) following local therapy for prostate cancer, and patients with metastatic castration-resistant prostate cancer (mCRPC). Results In the BCR patient population, early phase II trials of both pomegranate juice and extract showed significant lengthening of PSA doubling time (PSADT), and confirmed the safety of pomegranate products. While a placebo-controlled phase III trial determined that pomegranate extract did not significantly prolong PSADT in BCR patients, a preplanned subset analysis of patients with the manganese superoxide dismutase (MnSOD) AA genotype showed greater PSADT lengthening on the pomegranate extract arm. In the neoadjuvant population, a large trial demonstrated a significant increase in urolithin A and a non-significant reduction in 8-OHdG, a marker of oxidation in prostate cancer tissue, on the pomegranate arm vs. the placebo arm. In addition, a randomized clinical trial of a polyphenol-rich multi-component food supplement tablet, including 31.25% pomegranate extract, found significant slowing of PSA increase in the food supplement arm vs. placebo in men on active surveillance and those experiencing biochemical recurrence. Conclusions Pomegranate juice and extract are safe but did not significantly improve outcomes in BCR patients in a large placebo controlled trial. However a subset of BCR patients with the MnSOD AA genotype appear to respond positively to the antioxidant effects of pomegranate treatment. Phase II trials of 100% pomegranate products in neoadjuvant patients and patients with mCRPC were negative. A multi-component food supplement showed promising results in a phase II study in active surveillance and BCR patients. PMID:28440320

A Novel MiRNA-Based Predictive Model for Biochemical Failure Following Post-Prostatectomy Salvage Radiation Therapy

PubMed Central

Stegmaier, Petra; Drendel, Vanessa; Mo, Xiaokui; Ling, Stella; Fabian, Denise; Manring, Isabel; Jilg, Cordula A.; Schultze-Seemann, Wolfgang; McNulty, Maureen; Zynger, Debra L.; Martin, Douglas; White, Julia; Werner, Martin; Grosu, Anca L.; Chakravarti, Arnab

2015-01-01

Purpose To develop a microRNA (miRNA)-based predictive model for prostate cancer patients of 1) time to biochemical recurrence after radical prostatectomy and 2) biochemical recurrence after salvage radiation therapy following documented biochemical disease progression post-radical prostatectomy. Methods Forty three patients who had undergone salvage radiation therapy following biochemical failure after radical prostatectomy with greater than 4 years of follow-up data were identified. Formalin-fixed, paraffin-embedded tissue blocks were collected for all patients and total RNA was isolated from 1mm cores enriched for tumor (>70%). Eight hundred miRNAs were analyzed simultaneously using the nCounter human miRNA v2 assay (NanoString Technologies; Seattle, WA). Univariate and multivariate Cox proportion hazards regression models as well as receiver operating characteristics were used to identify statistically significant miRNAs that were predictive of biochemical recurrence. Results Eighty eight miRNAs were identified to be significantly (p<0.05) associated with biochemical failure post-prostatectomy by multivariate analysis and clustered into two groups that correlated with early (≤ 36 months) versus late recurrence (>36 months). Nine miRNAs were identified to be significantly (p<0.05) associated by multivariate analysis with biochemical failure after salvage radiation therapy. A new predictive model for biochemical recurrence after salvage radiation therapy was developed; this model consisted of miR-4516 and miR-601 together with, Gleason score, and lymph node status. The area under the ROC curve (AUC) was improved to 0.83 compared to that of 0.66 for Gleason score and lymph node status alone. Conclusion miRNA signatures can distinguish patients who fail soon after radical prostatectomy versus late failures, giving insight into which patients may need adjuvant therapy. Notably, two novel miRNAs (miR-4516 and miR-601) were identified that significantly improve prediction of biochemical failure post-salvage radiation therapy compared to clinico-histopathological factors, supporting the use of miRNAs within clinically used predictive models. Both findings warrant further validation studies. PMID:25760964

Estrogen receptor (α and β) but not androgen receptor expression is correlated with recurrence, progression and survival in post prostatectomy T3N0M0 locally advanced prostate cancer in an urban Greek population

PubMed Central

Megas, Georgios; Chrisofos, Michael; Anastasiou, Ioannis; Tsitlidou, Aida; Choreftaki, Theodosia; Deliveliotis, Charalampos

2015-01-01

The objective of this study was to evaluate the expression of estrogen receptors (ER(α) and ER(β)) and androgen receptors (ARs) as prognostic factors for biochemical recurrence, disease progression and survival in patients with pT3N0M0 prostate cancer (PCa) in an urban Greek population. A total of 100 consecutive patients with pT3N0M0 PCa treated with radical prostatectomy participated in the study. The mean age and follow-up were 64.2 and 6 years, respectively. The HSCORE was used for semi-quantitative analysis of the immunoreactivity of the receptors. The prognostic value of the ER(α) and ER(β) and AR was assessed in terms of recurrence, progression, and survival. AR expression was not associated with any of the above parameters; however, both ERs correlated with the prognosis. A univariate Cox regression analysis showed that ER(α) positive staining was significantly associated with a greater hazard for all outcomes. Increased ER(β) staining was significantly associated with a lower hazard for all outcomes in the univariate analysis. When both ER HSCORES were used for the analysis, it was found that patients with high ER(α) or low ER(β) HSCORES compared with patients with negatively stained ER(α) and >1.7 hSCORE ER(β) had 6.03, 10.93, and 10.53 times greater hazard for biochemical disease recurrence, progression of disease and death, respectively. Multiple Cox proportional hazard analyses showed that the age, preoperative prostate specific antigen, Gleason score and ERs were independent predictors of all outcomes. ER expression is an important prognosticator after radical prostatectomy in patients with pT3N0M0 PCa. By contrast, AR expression has limited prognostic value. PMID:25219910

Estrogen receptor (α and β) but not androgen receptor expression is correlated with recurrence, progression and survival in post prostatectomy T3N0M0 locally advanced prostate cancer in an urban Greek population.

PubMed

Megas, Georgios; Chrisofos, Michael; Anastasiou, Ioannis; Tsitlidou, Aida; Choreftaki, Theodosia; Deliveliotis, Charalampos

2015-01-01

The objective of this study was to evaluate the expression of estrogen receptors (ER(α) and ER(β)) and androgen receptors (ARs) as prognostic factors for biochemical recurrence, disease progression and survival in patients with pT3N0M0 prostate cancer (PCa) in an urban Greek population. A total of 100 consecutive patients with pT3N0M0 PCa treated with radical prostatectomy participated in the study. The mean age and follow-up were 64.2 and 6 years, respectively. The HSCORE was used for semi-quantitative analysis of the immunoreactivity of the receptors. The prognostic value of the ER(α) and ER(β) and AR was assessed in terms of recurrence, progression, and survival. AR expression was not associated with any of the above parameters; however, both ERs correlated with the prognosis. A univariate Cox regression analysis showed that ER(α) positive staining was significantly associated with a greater hazard for all outcomes. Increased ER(β) staining was significantly associated with a lower hazard for all outcomes in the univariate analysis. When both ER HSCORES were used for the analysis, it was found that patients with high ER(α) or low ER(β) HSCORES compared with patients with negatively stained ER(α) and >1.7 hSCORE ER(β) had 6.03, 10.93, and 10.53 times greater hazard for biochemical disease recurrence, progression of disease and death, respectively. Multiple Cox proportional hazard analyses showed that the age, preoperative prostate specific antigen, Gleason score and ERs were independent predictors of all outcomes. ER expression is an important prognosticator after radical prostatectomy in patients with pT3N0M0 PCa. By contrast, AR expression has limited prognostic value.

Salvage image guided radiation therapy to the prostate after cryotherapy failure.

PubMed

Hopper, Austin B; Sandhu, Ajay P S; Parsons, J Kellogg; Rose, Brent; Einck, John P

2018-01-01

Cryotherapy is an option for the primary treatment of localized prostate cancer, along with radical prostatectomy, external beam radiation therapy, and brachytherapy. Although it is known that local recurrence can occur in >20% of patients treated with primary cryotherapy, unfortunately there is a paucity of data on later salvage treatments. The use of external beam radiation therapy is an attractive option after cryotherapy failure, but there is little data on its efficacy and toxicity. We evaluated the biochemical control and complication rates of salvage dose-escalated image guided intensity modulated radiation therapy (IG-IMRT) after cryotherapy failure. Patients who were treated at our institution from 2005 to 2016 were reviewed for those who underwent cryotherapy as initial treatment followed by salvage IGRT. Patients were treated with dose-escalated IG-IMRT using standard treatment margins of 3 mm posterior and 7 mm in all other directions and daily cone beam computed tomography or kv imaging to implanted fiducial markers. Biochemical progression was defined in accordance with the Phoenix consensus conference definition. Eight patients were identified as having received post-cryotherapy salvage radiation within the study period. The median total dose was 77.7 Gy (range, 75.6-81.0 Gy). Median follow-up was 55 months (range, 6-88 months). Six patients remained biochemically controlled at the latest follow-up. One patient developed distant metastases after 22 months and one experienced biochemical failure at 30 months with no evidence of distant metastases. No patients experienced acute gastrointestinal toxicities of grade 2 or higher. There were no cases of late gastrointestinal or genitourinary toxicity. High-dose IG-IMRT results in high rates of salvage and extremely low rates of serious late toxicity for patients with locally recurrent prostate cancer after cryotherapy. Although the results are encouraging, given the small number of patients in this and other series, we remain cautious with regard to this treatment and believe the use of salvage radiation therapy after cryotherapy warrants further study.

Salvage High-intensity Focused Ultrasound for the Recurrent Prostate Cancer after Radiotherapy in Japan

NASA Astrophysics Data System (ADS)

Shoji, S.; Nakano, M.; Nagata, Y.; Uchida, T.

2011-09-01

To investigate the use of minimally invasive high-intensity focused ultrasound (HIFU) as a salvage therapy in men with localized prostate cancer recurrence following external beam radiotherapy (EBRT), brachytherapy or proton therapy. A review of 20 cases treated using the Sonablate® 500 HIFU device, between August 28, 2002 and June 1, 2010, was carried out. All men had presumed organ-confined, histologically confirmed recurrent prostate adenocarcinoma following radiation therapy. The mean (range) age was 65 (52-80) years with a mean PSA level before radiation therapy of 26.6 (4.8-118) ng/mL. The mean (range) period after radiation therapy to HIFU was 41 (4-96) months. All men with presumed, organ-confined, recurrent disease following EBRT in 13 patients, brachytherapy in 5 patients (4 patients with high-dose brachytherapy with In192 and 1 with low-dose brachytherapy with Au98) or proton therapy in 4 patients treated with salvage HIFU were included. The patients were followed for a mean (range) of 21 months. Biochemical disease-free survival (bDFS) rates in patients with low-, intermediate- and high risk groups were 100%, 85.7%, and 18.2%, respectively. All nine patients who received a post HIFU prostate biopsy showed no malignancy. Side-effects included urethral stricture in 4 of the 22 patients (18%) and urinary incontinence in 4 of the 22 patients (18%). Recto-urethral fistula occurred in one patient (5%). Salvage HIFU is a minimally invasive for patients with low-and intermediate risk group with comparable morbidity to other forms of salvage treatment.

Salvage high-intensity focused ultrasound for the recurrent prostate cancer after radiotherapy in Japan

NASA Astrophysics Data System (ADS)

Shoji, S.; Nakano, M.; Nagata, Y.; Uchida, T.

2012-10-01

Aim: to investigate the use of minimally invasive high-intensity focused ultrasound (HIFU) as a salvage therapy in men with localized prostate cancer recurrence following external beam radiotherapy (EBRT), brachytherapy or proton therapy. A review of 22 cases treated using the Sonablate® 500 HIFU device, between August 28, 2002 and April 1, 2010, was carried out. All men had presumed organ-confined, histologically confirmed recurrent prostate adenocarcinoma following radiation therapy. The mean (range) age was 65 (52-80) years with a mean PSA level before radiation therapy of 14.3 (5.7-118) ng/mL. The mean (range) period after radiation therapy to HIFU was 36 (4-96) months. All men with presumed, organ-confined, recurrent disease following EBRT in 14 patients, brachytherapy in 5 patients (4 patients with high-dose brachytherapy with In192 and 1 with low-dose brachytherapy with Au98) or proton therapy in 3 patients treated with salvage HIFU were included. The patients were followed for a mean (range) of 24 months. Biochemical disease-free survival (bDFS) rates in patients with low-, intermediate-and high risk groups were 100%, 86%, and 14%, respectively. All nine patients who received a post HIFU prostate biopsy showed no malignancy. Side-effects included urethral stricture in 4 of the 25 patients (16%) and urinary incontinence in 4 of the 25 patients (16%). Recto-urethral fistula occurred in one patient (4%). Salvage HIFU is a minimally invasive for patients with low-and intermediate risk group with comparable morbidity to other forms of salvage treatment.

Performance characteristics of prostate-specific antigen density and biopsy core details to predict oncological outcome in patients with intermediate to high-risk prostate cancer underwent robot-assisted radical prostatectomy.

PubMed

Yashi, Masahiro; Nukui, Akinori; Tokura, Yuumi; Takei, Kohei; Suzuki, Issei; Sakamoto, Kazumasa; Yuki, Hideo; Kambara, Tsunehito; Betsunoh, Hironori; Abe, Hideyuki; Fukabori, Yoshitatsu; Nakazato, Yoshimasa; Kaji, Yasushi; Kamai, Takao

2017-06-23

Many urologic surgeons refer to biopsy core details for decision making in cases of localized prostate cancer (PCa) to determine whether an extended resection and/or lymph node dissection should be performed. Furthermore, recent reports emphasize the predictive value of prostate-specific antigen density (PSAD) for further risk stratification, not only for low-risk PCa, but also for intermediate- and high-risk PCa. This study focused on these parameters and compared respective predictive impact on oncologic outcomes in Japanese PCa patients. Two-hundred and fifty patients with intermediate- and high-risk PCa according to the National Comprehensive Cancer Network (NCCN) classification, that underwent robot-assisted radical prostatectomy at a single institution, and with observation periods of longer than 6 months were enrolled. None of the patients received hormonal treatments including antiandrogens, luteinizing hormone-releasing hormone analogues, or 5-alpha reductase inhibitors preoperatively. PSAD and biopsy core details, including the percentage of positive cores and the maximum percentage of cancer extent in each positive core, were analyzed in association with unfavorable pathologic results of prostatectomy specimens, and further with biochemical recurrence. The cut-off values of potential predictive factors were set through receiver-operating characteristic curve analyses. In the entire cohort, a higher PSAD, the percentage of positive cores, and maximum percentage of cancer extent in each positive core were independently associated with advanced tumor stage ≥ pT3 and an increased index tumor volume > 0.718 ml. NCCN classification showed an association with a tumor stage ≥ pT3 and a Gleason score ≥8, and the attribution of biochemical recurrence was also sustained. In each NCCN risk group, these preoperative factors showed various associations with unfavorable pathological results. In the intermediate-risk group, the percentage of positive cores showed an independent predictive value for biochemical recurrence. In the high-risk group, PSAD showed an independent predictive value. PSAD and biopsy core details have different performance characteristics for the prediction of oncologic outcomes in each NCCN risk group. Despite the need for further confirmation of the results with a larger cohort and longer observation, these factors are important as preoperative predictors in addition to the NCCN classification for a urologic surgeon to choose a surgical strategy.

The Utility of PET/CT in the Planning of External Radiation Therapy for Prostate Cancer.

PubMed

Calais, Jeremie; Cao, Minsong; Nickols, Nicholas G

2018-04-01

Radiotherapy and radical prostatectomy are the definitive treatment options for patients with localized prostate cancer. A rising level of prostate-specific antigen after radical prostatectomy indicates prostate cancer recurrence, and these patients may still be cured with salvage radiotherapy. To maximize chance for cure, the irradiated volumes should completely encompass the extent of disease. Therefore, accurate estimation of the location of disease is critical for radiotherapy planning in both the definitive and the salvage settings. Current first-line imaging for prostate cancer has limited sensitivity for detection of disease both at initial staging and at biochemical recurrence. Integration of PET into routine evaluation of prostate cancer patients may improve both staging accuracy and radiotherapy planning. 18 F-FDG PET/CT is now routinely used in radiation planning for several cancer types. However, 18 F-FDG PET/CT has low sensitivity for prostate cancer. Additional PET probes evaluated in prostate cancer include 18 F-sodium fluoride, 11 C-acetate, 11 C- or 18 F-choline, 18 F-fluciclovine, and 68 Ga- or 18 F-labeled ligands that bind prostate-specific membrane antigen (PSMA). PSMA ligands appear to be the most sensitive and specific but have not yet received Food and Drug Administration New Drug Application approval for use in the United States. Retrospective and prospective investigations suggest a potential major impact of PET/CT on prostate radiation treatment planning. Prospective trials randomizing patients to routine radiotherapy planning versus PET/CT-aided planning may show meaningful clinical outcomes. Prospective clinical trials evaluating the addition of 18 F-fluciclovine PET/CT for planning of salvage radiotherapy with clinical endpoints are under way. Prospective trials evaluating the clinical impact of PSMA PET/CT on prostate radiation planning are indicated. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Dosimetry and first clinical evaluation of the new 18F-radiolabeled bombesin analogue BAY 864367 in patients with prostate cancer.

PubMed

Sah, Bert-Ram; Burger, Irene A; Schibli, Roger; Friebe, Matthias; Dinkelborg, Ludger; Graham, Keith; Borkowski, Sandra; Bacher-Stier, Claudia; Valencia, Ray; Srinivasan, Ananth; Hany, Thomas F; Mu, Linjing; Wild, Peter J; Schaefer, Niklaus G

2015-03-01

The aim of this first-in-man study was to demonstrate the feasibility, safety, and tolerability, as well as provide dosimetric data and evaluate the imaging properties, of the bombesin analogue BAY 864367 for PET/CT in a small group of patients with primary and recurrent prostate cancer (PCa). Ten patients with biopsy-proven PCa (5 with primary PCa and 5 with prostate-specific antigen recurrence after radical prostatectomy) were prospectively selected for this exploratory clinical trial with BAY 864367, a new (18)F-labeled bombesin analogue. PET scans were assessed at 6 time points, up to 110 min after intravenous administration of 302 ± 11 MBq of BAY 864367. Imaging results were compared with (18)F-fluorocholine PET/CT scans. Dosimetry was calculated using the OLINDA/EXM software. Three of 5 patients with primary disease showed positive tumor delineation in the prostate, and 2 of 5 patients with biochemical relapse showed a lesion suggestive of recurrence on the BAY 864367 scan. Tumor-to-background ratio averaged 12.9 ± 7.0. The ratio of malignant prostate tissue to normal prostate tissue was 4.4 ± 0.6 in 3 patients with tracer uptake in the primary PCa. Mean effective dose was 4.3 ± 0.3 mSv/patient (range, 3.7-4.9 mSv). BAY 864367, a novel (18)F-labeled bombesin tracer, was successfully investigated in a first-in-man clinical trial of PCa and showed favorable dosimetric values. Additionally, the application was safe and well tolerated. The tracer delineated tumors in a subset of patients, demonstrating the potential of gastrin-releasing-peptide receptor imaging. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

68Ga-PSMA-PET/CT in Patients With Biochemical Prostate Cancer Recurrence and Negative 18F-Choline-PET/CT.

PubMed

Bluemel, Christina; Krebs, Markus; Polat, Bülent; Linke, Fränze; Eiber, Matthias; Samnick, Samuel; Lapa, Constantin; Lassmann, Michael; Riedmiller, Hubertus; Czernin, Johannes; Rubello, Domenico; Bley, Thorsten; Kropf, Saskia; Wester, Hans-Juergen; Buck, Andreas K; Herrmann, Ken

2016-07-01

Investigating the value of Ga-PSMA-PET/CT in biochemically recurring prostate cancer patients with negative F-choline-PET/CT. One hundred thirty-nine consecutive patients with biochemical recurrence after curative (surgery and/or radiotherapy) therapy were offered participation in this sequential clinical imaging approach. Patients first underwent an F-choline-PET/CT. If negative, an additional Ga-PSMA-PET/CT was offered. One hundred twenty-five of 139 eligible patients were included in the study; 32 patients underwent additional Ga-PSMA-PET/CT. Patients with equivocal findings (n = 5) on F-choline-PET/CT and those who declined the additional Ga-PSMA-PET/CT (n = 9) were excluded. Images were analyzed visually for the presence of suspicious lesions. Findings on PET/CT were correlated with PSA level, PSA doubling time (dt), and PSA velocity (vel). The overall detection rates were 85.6% (107/125) for the sequential imaging approach and 74.4% (93/125) for F-choline-PET/CT alone. Ga-PSMA-PET/CT detected sites of recurrence in 43.8% (14/32) of the choline-negative patients. Detection rates of the sequential imaging approach and F-choline-PET/CT alone increased with higher serum PSA levels and PSA vel. Subgroup analysis of Ga-PSMA-PET/CT in F-choline negative patients revealed detection rates of 28.6%, 45.5%, and 71.4% for PSA levels of 0.2 or greater to less than 1 ng/mL, 1 to 2 ng/mL, and greater than 2 ng/mL, respectively. The sequential imaging approach designed to limit Ga-PSMA imaging to patients with negative choline scans resulted in high detection rates. Ga-PSMA-PET/CT identified sites of recurrent disease in 43.8% of the patients with negative F-choline PET/CT scans.

68Ga-PSMA-PET/CT in Patients With Biochemical Prostate Cancer Recurrence and Negative 18F-Choline-PET/CT

PubMed Central

Bluemel, Christina; Krebs, Markus; Polat, Bülent; Linke, Fränze; Eiber, Matthias; Samnick, Samuel; Lapa, Constantin; Lassmann, Michael; Riedmiller, Hubertus; Czernin, Johannes; Rubello, Domenico; Bley, Thorsten; Kropf, Saskia; Wester, Hans-Juergen; Buck, Andreas K.; Herrmann, Ken

2016-01-01

Purpose Investigating the value of 68Ga-PSMA-PET/CT in biochemically recurring prostate cancer patients with negative 18F-choline-PET/CT. Patients and Methods One hundred thirty-nine consecutive patients with biochemical recurrence after curative (surgery and/or radiotherapy) therapy were offered participation in this sequential clinical imaging approach. Patients first underwent an 18F-choline-PET/CT. If negative, an additional 68Ga-PSMA-PET/CTwas offered. One hundred twenty-five of 139 eligible patients were included in the study; 32 patients underwent additional 68Ga-PSMA-PET/CT. Patients with equivocal findings (n = 5) on 18F-choline-PET/CT and those who declined the additional 68Ga-PSMA-PET/CT (n = 9) were excluded. Images were analyzed visually for the presence of suspicious lesions. Findings on PET/CT were correlated with PSA level, PSA doubling time (dt), and PSA velocity (vel). Results The overall detection rates were 85.6% (107/125) for the sequential imaging approach and 74.4% (93/125) for 18F-choline-PET/CT alone. 68Ga-PSMA-PET/CT detected sites of recurrence in 43.8% (14/32) of the choline-negative patients. Detection rates of the sequential imaging approach and 18F-choline-PET/CT alone increased with higher serum PSA levels and PSA vel. Subgroup analysis of 68Ga-PSMA-PET/CT in 18F-choline negative patients revealed detection rates of 28.6%, 45.5%, and 71.4% for PSA levels of 0.2 or greater to less than 1 ng/mL, 1 to 2 ng/mL, and greater than 2 ng/mL, respectively. Conclusions The sequential imaging approach designed to limit 68Ga-PSMA imaging to patients with negative choline scans resulted in high detection rates. 68Ga-PSMA-PET/CT identified sites of recurrent disease in 43.8% of the patients with negative 18F-choline PET/CT scans. PMID:26975008

Salvage Radiotherapy After Postprostatectomy Biochemical Failure: Does Pretreatment Radioimmunoscintigraphy Help Select Patients with Locally Confined Disease?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liauw, Stanley L.; Weichselbaum, Ralph R.; Zagaja, Gregory P.

2008-08-01

Purpose: Radioimmunoscintigraphy (RIS) has the potential to demonstrate early recurrences after prostatectomy and might be useful in selecting patients for salvage radiotherapy (RT). Methods: A total of 82 patients with adenocarcinoma of the prostate were treated with salvage RT between 1988 and 2005, for an elevated prostate-specific antigen (PSA) level after prostatectomy. Of the 82 patients, 32% had Gleason score 6 or less disease, 54% Gleason score 7 disease, 70% had Stage pT3 disease, 55% had positive margins, and 5% had pathologic lymph node involvement. The median pre-RT PSA level was 0.63 ng/mL. Of the 82 patients, 47 (57%) hadmore » a pre-RT RIS (ProstaScint) scan, which was used for both patient selection and target delineation. The RT regimen was a median dose of 66 Gy to the prostate bed. Also, 64% received androgen deprivation therapy. Biochemical failure was defined as a PSA level >0.1 ng/mL and increasing. Results: Patients with a pre-RT RIS scan had a lower preoperative PSA level (p = 0.0240) and shorter follow-up (p = 0.0221) than those without RIS. With a median follow-up of 44 months, the biochemical control rate was 56% at 3 years and 48% at 5 years. Margin status was the only factor associated with biochemical control on univariate (p = 0.0055) and multivariate (p = 0.0044) analysis. Patients who had prostate bed-only uptake on RIS (n = 38) did not have improved outcomes, with biochemical control rates of 51% at 3 years and 40% at 5 years. Conclusion: Patients treated with salvage RT had modest responses. Patients who were selected for treatment with RIS did not have better biochemical outcomes. Our results indicated that patients with positive margins were most likely to benefit from salvage RT.« less

Salvage Radiation Therapy Dose Response for Biochemical Failure of Prostate Cancer After Prostatectomy—A Multi-Institutional Observational Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pisansky, Thomas M., E-mail: pisansky.thomas@mayo.edu; Agrawal, Shree; Hamstra, Daniel A.

Purpose: To determine whether a dose-response relationship exists for salvage radiation therapy (RT) of biochemical failure after prostatectomy for prostate cancer. Methods and Materials: Individual data from 1108 patients who underwent salvage RT at 10 academic centers were pooled. The cohort was enriched for selection criteria more likely associated with tumor recurrence in the prostate bed (margin positive and pre-RT prostate-specific antigen [PSA] level of ≤2.0 ng/mL) and without the confounding of planned androgen suppression. The cumulative incidence of biochemical failure and distant metastasis over time was computed, and competing risks hazard regression models were used to investigate the association betweenmore » potential predictors and these outcomes. The association of radiation dose with outcomes was the primary focus. Results: With a 65.2-month follow-up duration, the 5- and 10-year estimates of freedom from post-RT biochemical failure (PSA level >0.2 ng/mL and rising) was 63.5% and 49.8%, respectively, and the cumulative incidence of distant metastasis was 12.4% by 10 years. A Gleason score of ≥7, higher pre-RT PSA level, extraprostatic tumor extension, and seminal vesicle invasion were associated with worse biochemical failure and distant metastasis outcomes. A salvage radiation dose of ≥66.0 Gy was associated with a reduced cumulative incidence of biochemical failure, but not of distant metastasis. Conclusions: The use of salvage radiation doses of ≥66.0 Gy are supported by evidence presented in the present multicenter pooled analysis of individual patient data. The observational reporting method, limited sample size, few distant metastasis events, modest follow-up duration, and elective use of salvage therapy might have diminished the opportunity to identify an association between the radiation dose and this endpoint.« less

Evaluation of Serum Calcium as a Predictor of Biochemical Recurrence following Salvage Radiation Therapy for Prostate Cancer

PubMed Central

Peterson, Jennifer L.; Buskirk, Steven J.; Heckman, Michael G.; Parker, Alexander S.; Diehl, Nancy N.; Tzou, Katherine S.; Paryani, Nitesh N.; Ko, Stephen J.; Daugherty, Larry C.; Vallow, Laura A.; Pisansky, Thomas M.

2013-01-01

Background. Previous reports have shown a positive association between serum calcium level and prostate cancer mortality. However, there is no data regarding whether higher serum calcium levels are associated with increased risk of biochemical recurrence (BCR) following salvage radiation therapy (SRT) for prostate cancer. Herein, we evaluate the association between pretreatment serum calcium levels and BCR in a cohort of men who underwent SRT. Methods. We evaluated 165 patients who underwent SRT at our institution. Median dose was 65.0 Gy (range: 54.0–72.4 Gy). We considered serum calcium as both a continuous variable and a 3-level categorical variable (low [≤9.0 mg/dL], moderate [>9.0 mg/dL and ≤9.35 mg/dL], and high [>9.35 mg/dL]) based on sample tertiles. Results. We observed no evidence of a linear association between serum calcium and BCR (relative risk (RR): 0.96, P = 0.76). Compared to men with low calcium, there was no significantly increased risk of BCR for men with moderate (RR: 0.94, P = 0.79) or high (RR: 1.08, P = 0.76) serum calcium levels. Adjustment for clinical, pathological, and SRT characteristics in multivariable analyses did not alter these findings. Conclusion. Our results provide evidence that pretreatment serum calcium is unlikely to be a useful tool in predicting BCR risk following SRT. PMID:23606986

Diagnostic Challenges in Prostate Cancer and 68Ga-PSMA PET Imaging: A Game Changer?

PubMed

Zaman, Maseeh uz; Fatima, Nosheen; Zaman, Areeba; Sajid, Mahwsih; Zaman, Unaiza; Zaman, Sidra

2017-10-26

Prostate cancer (PC) is the most frequent solid tumor in men and the third most common cause of cancer mortality among men in developed countries. Current imaging modalities like ultrasound (US), computerized tomography (CT), magnetic resonance imaging (MRI) and choline based positron emission (PET) tracing have disappointing sensitivity for detection of nodal metastasis and small tumor recurrence. This poses a diagnostic challenge in staging of intermediate to high risk PC and restaging of patients with biochemical recurrence (PSA >0.2 ng/ml). Gallium-68 labeled prostate specific membrane antigen (68Ga-PSMA) PET imaging has now emerged with a higher diagnostic yield. 68Ga-PSMA PET/CT or PET/MRI can be expected to offer a one-stop-shop for staging and restaging of PC. PSMA ligands labeled with alpha and beta emitters have also shown promising therapeutic efficacy for nodal, bone and visceral metastasis. Therefore a PSMA based theranostics approach for detection, staging, treatment, and follow-up of PC would appear to be highly valuable to achieve personalized PC treatment. Creative Commons Attribution License

Robot-assisted Salvage Lymph Node Dissection for Clinically Recurrent Prostate Cancer.

PubMed

Montorsi, Francesco; Gandaglia, Giorgio; Fossati, Nicola; Suardi, Nazareno; Pultrone, Cristian; De Groote, Ruben; Dovey, Zach; Umari, Paolo; Gallina, Andrea; Briganti, Alberto; Mottrie, Alexandre

2017-09-01

Salvage lymph node dissection has been described as a feasible treatment for the management of prostate cancer patients with nodal recurrence after primary treatment. To report perioperative, pathologic, and oncologic outcomes of robot-assisted salvage nodal dissection (RASND) in patients with nodal recurrence after radical prostatectomy (RP). We retrospectively evaluated 16 patients affected by nodal recurrence following RP documented by positive positron emission tomography/computed tomography scan. Surgery was performed using DaVinci Si and Xi systems. A pelvic nodal dissection that included lymphatic stations overlying the external, internal, and common iliac vessels, the obturator fossa, and the presacral nodes was performed. In 13 (81.3%) patients a retroperitoneal lymph node dissection that included all nodal tissue located between the aortic bifurcation and the renal vessels was performed. Perioperative outcomes consisted of operative time, blood loss, length of hospital stay, and complications occurred within 30 d after surgery. Biochemical response (BR) was defined as a prostate-specific antigen level <0.2 ng/ml at 40 d after RASND. Median operative time, blood loss, and length of hospital stay were 210min, 250ml, and 3.5 d. The median number of nodes removed was 16.5. Positive lymph nodes were detected in 11 (68.8%) patients. Overall, four (25.0%) and five (31.2%) patients experienced intraoperative and postoperative complications, respectively. Overall, one (6.3%) and four (25.0%) patients had Clavien I and II complications within 30 d after RASND, respectively. Overall, five (33.3%) patients experienced BR after surgery. Our study is limited by the small cohort of patients evaluated and by the follow-up duration. RASND represents a feasible procedure in patients with nodal recurrence after RP and provides acceptable short-term oncologic outcomes, where one out of three patients experience BR immediately after surgery. Long-term data are needed to confirm the effectiveness of this approach. We report our initial experience with robot-assisted salvage nodal dissection for the management of patients with lymph node recurrence after radical prostatectomy. This technique represents a feasible and effective approach, where no high-grade complications were recorded and one out of three patients experienced biochemical response at 40 d after surgery. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Combinations of elevated tissue miRNA-17-92 cluster expression and serum prostate-specific antigen as potential diagnostic biomarkers for prostate cancer.

PubMed

Feng, Sujuan; Qian, Xiaosong; Li, Han; Zhang, Xiaodong

2017-12-01

The aim of the present study was to investigate the effectiveness of the miR-17-92 cluster as a disease progression marker in prostate cancer (PCa). Reverse transcription-quantitative polymerase chain reaction analysis was used to detect the microRNA (miR)-17-92 cluster expression levels in tissues from patients with PCa or benign prostatic hyperplasia (BPH), in addition to in PCa and BPH cell lines. Spearman correlation was used for comparison and estimation of correlations between miRNA expression levels and clinicopathological characteristics such as the Gleason score and prostate-specific antigen (PSA). Receiver operating curve (ROC) analysis was performed for evaluation of specificity and sensitivity of miR-17-92 cluster expression levels for discriminating patients with PCa from patients with BPH. Kaplan-Meier analysis was plotted to investigate the predictive potential of miR-17-92 cluster for PCa biochemical recurrence. Expression of the majority of miRNAs in the miR-17-92 cluster was identified to be significantly increased in PCa tissues and cell lines. Bivariate correlation analysis indicated that the high expression of unregulated miRNAs was positively correlated with Gleason grade, but had no significant association with PSA. ROC curves demonstrated that high expression of miR-17-92 cluster predicted a higher diagnostic accuracy compared with PSA. Improved discriminating quotients were observed when combinations of unregulated miRNAs with PSA were used. Survival analysis confirmed a high combined miRNA score of miR-17-92 cluster was associated with shorter biochemical recurrence interval. miR-17-92 cluster could be a potential diagnostic and prognostic biomarker for PCa, and the combination of the miR-17-92 cluster and serum PSA may enhance the accuracy for diagnosis of PCa.

PET imaging in adaptive radiotherapy of prostate tumors.

PubMed

Beuthien-Baumann, Bettina; Koerber, Stefan A

2018-06-04

The integration of data from positron-emission-tomography, combined with computed tomography as PET/CT or combined with magnet resonance imaging as PET/MRI, into radiation treatment planning of prostate cancer is gaining higher impact with the development of more sensitive and specific radioligands. The classic PET-tracer for prostate cancer imaging are [11C]choline and [11C]acetate, which are currently outperformed by ligands binding to the prostate-specific- membrane-antigen (PSMA). [68Ga]PSMA-11, which is the most frequently applied tracer, has shown to detect lymph node metastases, local recurrences, distant metastases and intraprostatic foci with high sensitivity, even at relatively low PSA levels. The results from PET-imaging may influence radiotherapeutic (RT) management at different stages of the disease i.e. during primary staging or biochemical recurrence, when the detection of distant metastases may alter the curative treatment concept into a palliative approach. On the other hand, the clinical target volume could be adapted by visualizing lymph node metastases at locations, which might not have been suspicious on morphologic imaging alone. The treatment plan might contain a boost to the dominant intraprostatic lesion, which could be delineated by a combination of PET-tracer uptake and multiparametric MRI. Therefore, PSMA-PET imaging is well suited for being integrated into prostate radiation planning. However, further prospective trials evaluating the impact on oncological outcome are indicated.

False Positive Uptake in Bilateral Gynecomastia on 68Ga-PSMA PET/CT Scan.

PubMed

Sasikumar, Arun; Joy, Ajith; Nair, Bindu P; Pillai, M R A; Madhavan, Jayaprakash

2017-09-01

A 66-year-old man on hormonal therapy with prostate cancer was referred for Ga-PSMA PET/CT scan for biochemical recurrence. Ga-PSMA PET/CT scan detected moderate heterogeneous tracer concentration in bilateral breast parenchyma, in addition to the abnormal tracer concentration in enlarged prostate gland, right external iliac lymph node, and sclerotic lesion in L4 vertebra. On clinical examination, he was found to have bilateral gynecomastia. Abnormal concentration of Ga-PSMA in breast cancer is now well known, and in this context, it is important to know that tracer localization can occur in gynecomastia as well, as evidenced in this case.

Image Guided Hypofractionated Postprostatectomy Intensity Modulated Radiation Therapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lewis, Stephen L.; Patel, Pretesh; Song, Haijun

2016-03-01

Purpose: Hypofractionated radiation therapy (RT) has promising long-term biochemical relapse-free survival (bRFS) with comparable toxicity for definitive treatment of prostate cancer. However, data reporting outcomes after adjuvant and salvage postprostatectomy hypofractionated RT are sparse. Therefore, we report the toxicity and clinical outcomes after postprostatectomy hypofractionated RT. Methods and Materials: From a prospectively maintained database, men receiving image guided hypofractionated intensity modulated RT (HIMRT) with 2.5-Gy fractions constituted our study population. Androgen deprivation therapy was used at the discretion of the radiation oncologist. Acute toxicities were graded according to the Common Terminology Criteria for Adverse Events version 4.0. Late toxicities weremore » scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. Biochemical recurrence was defined as an increase of 0.1 in prostate-specific antigen (PSA) from posttreatment nadir or an increase in PSA despite treatment. The Kaplan-Meier method was used for the time-to-event outcomes. Results: Between April 2008 and April 2012, 56 men received postoperative HIMRT. The median follow-up time was 48 months (range, 21-67 months). Thirty percent had pre-RT PSA <0.1; the median pre-RT detectable PSA was 0.32 ng/mL. The median RT dose was 65 Gy (range, 57.5-65 Gy). Ten patients received neoadjuvant and concurrent hormone therapy. Posttreatment acute urinary toxicity was limited. There was no acute grade 3 toxicity. Late genitourinary (GU) toxicity of any grade was noted in 52% of patients, 40% of whom had pre-RT urinary incontinence. The 4-year actuarial rate of late grade 3 GU toxicity (exclusively gross hematuria) was 28% (95% confidence interval [CI], 16%-41%). Most grade 3 GU toxicity resolved; only 7% had persistent grade ≥3 toxicity at the last follow-up visit. Fourteen patients experienced biochemical recurrence at a median of 20 months after radiation. The 4-year bPFS rate was 75% (95% CI, 63%-87%). Conclusions: The biochemical control in this series appears promising, although relatively short follow-up may lead to overestimation. Late grade 3 GU toxicity was higher than anticipated with hypofractionated radiation of 65 Gy to the prostate bed, although most resolved.« less

Identification of Differentially Expressed Proteins in Direct Expressed Prostatic Secretions of Men with Organ-confined Versus Extracapsular Prostate Cancer*

PubMed Central

Kim, Yunee; Ignatchenko, Vladimir; Yao, Cindy Q.; Kalatskaya, Irina; Nyalwidhe, Julius O.; Lance, Raymond S.; Gramolini, Anthony O.; Troyer, Dean A.; Stein, Lincoln D.; Boutros, Paul C.; Medin, Jeffrey A.; Semmes, O. John; Drake, Richard R.; Kislinger, Thomas

2012-01-01

Current protocols for the screening of prostate cancer cannot accurately discriminate clinically indolent tumors from more aggressive ones. One reliable indicator of outcome has been the determination of organ-confined versus nonorgan-confined disease but even this determination is often only made following prostatectomy. This underscores the need to explore alternate avenues to enhance outcome prediction of prostate cancer patients. Fluids that are proximal to the prostate, such as expressed prostatic secretions (EPS), are attractive sources of potential prostate cancer biomarkers as these fluids likely bathe the tumor. Direct-EPS samples from 16 individuals with extracapsular (n = 8) or organ-confined (n = 8) prostate cancer were used as a discovery cohort, and were analyzed in duplicate by a nine-step MudPIT on a LTQ-Orbitrap XL mass spectrometer. A total of 624 unique proteins were identified by at least two unique peptides with a 0.2% false discovery rate. A semiquantitative spectral counting algorithm identified 133 significantly differentially expressed proteins in the discovery cohort. Integrative data mining prioritized 14 candidates, including two known prostate cancer biomarkers: prostate-specific antigen and prostatic acid phosphatase, which were significantly elevated in the direct-EPS from the organ-confined cancer group. These and five other candidates (SFN, MME, PARK7, TIMP1, and TGM4) were verified by Western blotting in an independent set of direct-EPS from patients with biochemically recurrent disease (n = 5) versus patients with no evidence of recurrence upon follow-up (n = 10). Lastly, we performed proof-of-concept SRM-MS-based relative quantification of the five candidates using unpurified heavy isotope-labeled synthetic peptides spiked into pools of EPS-urines from men with extracapsular and organ-confined prostate tumors. This study represents the first efforts to define the direct-EPS proteome from two major subclasses of prostate cancer using shotgun proteomics and verification in EPS-urine by SRM-MS. PMID:22986220

Disseminated Tumor Cells in Prostate Cancer Patients after Radical Prostatectomy and without Evidence of Disease Predicts Biochemical Recurrence

PubMed Central

Morgan, Todd M.; Lange, Paul H.; Porter, Michael P.; Lin, Daniel W.; Ellis, William J.; Gallaher, Ian S.; Vessella, Robert L.

2011-01-01

Purpose Men with apparently localized prostate cancer often relapse years after radical prostatectomy (RP). We sought to determine if epithelial-like cells identified from bone marrow (BM) in patients after RP (commonly called disseminated tumor cells, DTC) were associated with biochemical recurrence (BR). Experimental Design We obtained BM aspirates from 569 men prior to RP and from 34 healthy men with PSA<2.5 ng/ml to establish a comparison group. Additionally, an analytic cohort consisting of 98 patients after RP with no evidence of disease (NED) was established to evaluate the relationship between DTC and BR. Epithelial cells in the BM were detected by magnetic bead enrichment with antibodies to CD45 and CD61 (negative selection) followed by antibodies to human epithelial antigen (positive selection) and confirmation with FITC-labeled anti-BerEP4 antibody. Results DTC were present in 72% (408/569) of patients prior to RP. There was no correlation with pathologic stage, Gleason grade, or pre-operative PSA. Three of 34 controls (8.8%) had DTC present. In patients NED post-RP, DTC were present in 56/98 (57%). DTC were detected in 12/14 (86%) NED patients post-RP who subsequently suffered BR. Presence of DTC in NED patients was an independent predictor of recurrence (HR 6.9, CI 1.03–45.9). Conclusions Approximately 70% of men undergoing RP had DTC detected in their BM prior to surgery, suggesting that these cells escape early in the disease. Though pre-operative DTC status does not correlate with pathologic risk factors, persistence of DTC after RP in NED patients was an independent predictor of recurrence. PMID:19147774

A Diet, Physical Activity, and Meditation Intervention in Men With Rising Prostate-Specific Antigen (PSA)

DTIC Science & Technology

2007-05-01

AD_________________ Award Number: DAMD17-03-1-0139 TITLE: A Diet , Physical Activity, and...To) 1 May 2003 – 30 Apr 2007 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER A Diet , Physical Activity, and Meditation Intervention in Men with...asymptomatic men with biochemically recurrent PrCA, as reflected by the PSA rise, is favorably affected by an intensive, vegetable-based diet , plus

PET/CT with (11)C-choline for evaluation of prostate cancer patients with biochemical recurrence: meta-analysis and critical review of available data.

PubMed

Fanti, Stefano; Minozzi, Silvia; Castellucci, Paolo; Balduzzi, Sara; Herrmann, Ken; Krause, Bernd Joachim; Oyen, Wim; Chiti, Arturo

2016-01-01

For the last decade PET and PET/CT with (11)C-choline have been proposed for the evaluation of prostate cancer (PC), but the diagnostic performance of (11)C-choline PET/CT is still a matter of debate. We performed a comprehensive review of the most important clinical application of (11)C-choline PET, restaging of patients with biochemical relapse, following a rigorous methodological approach and including assessment of the risk of bias. We conducted a systematic review and meta-analysis of the literature assessing (11)C-choline PET/CT for its accuracy in the diagnosis and ability to detect the site of recurrence of PC in the restaging of patients with biochemical recurrence after initial treatment with curative intent. We performed a comprehensive literature search of PubMed and the Cochrane Library to determine the accuracy for the detection of the site of recurrence (prostate bed recurrences, metastatic spread to locoregional pelvic lymph nodes or distant metastases). Only studies with a reference standard (for prostatic bed histopathology, for histopathology or biopsy of distant metastases or a composite reference standard with clinical follow-up of at least 12 months, correlative imaging and clinical data) were included. Overall 425 studies were retrieved, of which 43 were judged as potentially relevant and 29 with 2,686 participants were finally included. Of these 29 studies, 18 reported results for any relapse, All 18 studies, with a total of 2,126 participants, reported detection rates. The pooled rate was 62 % (95 % CI 53 - 71 %). Of the 18 studies, 12 with 1,270 participants reported useful data to derive sensitivity and specificity. The pooled sensitivity was 89 % (95 % CI 83 - 93 %) and the pooled specificity was 89 % (95 % CI 73 - 96 %). Of 11 studies reporting results for local relapse, 9 with 993 participants reported detection rates. The pooled rate was 27 % (95 % CI 16 - 38 %). Six studies with 491 participants reported sensitivity and specificity. The pooled sensitivity was 61 % (95 % CI 40 - 80 %) and the pooled specificity was 97 % (95 % CI 87 - 99 %). Ten studies reported results for lymph nodes and distant metastases. For nodal disease, 7 studies with 752 participants reported detection rates. The pooled rate was 36 % (95 % CI 22 - 50 %). For bone metastases, 8 studies with 775 participants reported detection rates. The pooled rate was 25 % (95 % CI 16 - 34 %). There is a significant amount of (11)C-choline PET data published showing a high degree of consistency in inclusion criteria, acquisition protocols and scan interpretation criteria. Furthermore, the quality of the data derived limited to the same standard of reference was acceptable. Despite a high variability in the observed prevalence of any relapse, the diagnostic performance of (11)C-choline PET was in line with previous meta-analyses. Our data confirm the very good accuracy of (11)C-choline PET for detection of lymph node metastases and/or distant lesions in a single examination in patients with biochemical relapse.

Early hypofractionated salvage radiotherapy for postprostatectomy biochemical recurrence.

PubMed

Kruser, Tim J; Jarrard, David F; Graf, Andrew K; Hedican, Sean P; Paolone, David R; Wegenke, John D; Liu, Glenn; Geye, Heather M; Ritter, Mark A

2011-06-15

Postprostatectomy adjuvant or salvage radiotherapy, when using standard fractionation, requires 6.5 to 8 weeks of treatment. The authors report on the safety and efficacy of an expedited radiotherapy course for salvage prostate radiotherapy. A total of 108 consecutive patients were treated with salvage radiation therapy to 65 grays (Gy) in 26 fractions of 2.5 Gy. Median follow-up was 32.4 months. Median presalvage prostate-specific antigen (PSA) was 0.44 (range, 0.05-9.50). Eighteen (17%) patients received androgen deprivation after surgery or concurrently with radiation. The actuarial freedom from biochemical failure for the entire group at 4 years was 67% ± 5.3%. An identical 67% control rate was seen at 5 years for the first 50 enrolled patients, whose median follow-up was longer at 43 months. One acute grade 3 genitourinary toxicity occurred, with no acute grade 3 gastrointestinal and no late grade 3 toxicities observed. On univariate analysis, higher Gleason score (P = .006), PSA doubling time ≤12 months (P = .03), perineural invasion (P = .06), and negative margins (P = .06) showed association with unsuccessful salvage. On multivariate analysis, higher Gleason score (P = .057) and negative margins (P = .088) retained an association with biochemical failure. Hypofractionated radiotherapy (65 Gy in 2.5 Gy fractions in about 5 weeks) reduces the length of treatment by from 1-½ to 3 weeks relative to other treatment schedules commonly used, produces low rates of toxicity, and demonstrates encouraging efficacy at 4 to 5 years. Hypofractionation may provide a convenient, resource-efficient, and well-tolerated salvage approach for the estimated 20,000 to 35,000 US men per year experiencing biochemical recurrence after prostatectomy. Copyright © 2010 American Cancer Society.

PSMA PET/CT with Glu-urea-Lys-(Ahx)-[⁶⁸Ga(HBED-CC)] versus 3D CT volumetric lymph node assessment in recurrent prostate cancer.

PubMed

Giesel, Frederik L; Fiedler, H; Stefanova, M; Sterzing, F; Rius, M; Kopka, K; Moltz, J H; Afshar-Oromieh, A; Choyke, P L; Haberkorn, U; Kratochwil, C

2015-11-01

PET/CT with the PSMA ligand is a powerful new method for the early detection of nodal metastases in patients with biochemical relapse. The purpose of this retrospective investigation was to evaluate the volume and dimensions of nodes identified by Glu-urea-Lys-(Ahx)-[(68)Ga(HBED-CC)] ((68)Ga-PSMA-11) in the setting of recurrent prostate cancer. All PET/CT images were acquired 60 ± 10 min after intravenous injection of (68)Ga-PSMA-11 (mean dose 176 MBq). In 21 patients with recurrent prostate cancer and rising PSA, 49 PSMA-positive lymph nodes were identified. Using semiautomated lymph node segmentation software, node volume and short-axis and long-axis dimensions were measured and compared with the maximum standardized uptake values (SUVmax). Round nodes greater than or equal to 8 mm were considered positive by morphological criteria alone. The percentage of nodes identified by elevated SUVmax but not by conventional morphological criteria was determined. The mean volume of (68)Ga-PSMA-11-positive nodes was 0.5 ml (range 0.2 - 2.3 ml), and the mean short-axis diameter was 5.8 mm (range 2.4 - 13.3 mm). In 7 patients (33.3 %) with 31 PSMA-positive nodes only 11 (36 %) were morphologically positive based on diameters >8 mm on CT. In the remaining 14 patients (66.7 %), 18 (37 %) of PSMA positive lymph nodes had short-axis diameters <8 mm with a mean short-axis diameter of 5.0 mm (range 2.4 - 7.9 mm). Thus, in this population, (68)Ga-PSMA-11 PET/CT detected nodal recurrence in two-thirds of patients who would have been missed using conventional morphological criteria. (68)Ga-PSMA-11 PET/CT is more sensitive than CT based 3D volumetric lymph node evaluation in determining the node status of patients with recurrent prostate cancer, and is a promising method of restaging prostate cancers in this setting.

Correlation between prolonged use of aspirin and prognostic risk in prostate cancer.

PubMed

Dell'Atti, Lucio

2014-01-01

In recent years the role of inflammation in cancer etiology has gained attention and several studies have suggested that acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs may have chemopreventive activity and reduce the risk of prostate cancer. We investigated whether there is a correlation between prolonged use of aspirin and prognostic risk in prostate cancer. From January 2002 to December 2007 we performed 385 radical prostatectomies for localized prostate cancer. Patients were divided into 2 groups: group A (GA) comprised 174 patients who took aspirin 100 mg once daily for 2 years or more; group B (GB) consisted of 211 patients who did not take NSAIDs, or only occasionally. To evaluate the correlation between aspirin use and prognostic risk in prostate cancer we examined the following factors: biochemical recurrence, percentage of positive surgical margins, pathological stage, pathological Gleason score, percentage of positive lymph nodes, and preoperative PSA level. There was no statistical difference in preoperative PSA levels (6.5 and 6.9 ng/mL; P = 0.045) between the 2 groups. The incidence of positive surgical margins was 18.9% in GA and 28.9% in GB (P <0.002). The percentage of positive lymph nodes in patients with positive surgical margins in GB (47.5%) was statistically higher than that in GA (27.2%). With an average follow-up period of 4.6 years, 22.7% of patients in GA and 32.7% in GB developed biochemical recurrence. In the stratified analysis we observed significant differences in the association between prediagnostic aspirin use and prognostic risk for patients with Gleason score 7 and T2 stage of disease. The daily use of aspirin was significantly associated with a lower risk of disease progression, with a hazard ratio of 0.92 (95% CI 0.85-0.99). These results provide further evidence that aspirin may have chemopreventive activity against prostate cancer and highlight the need for additional research. Additional studies with more detailed exposure measurement are warranted to evaluate questions about dose, the best age to begin treatment, and the duration of therapy.

Prospective evaluation of fluciclovine (18F) PET-CT and MRI in detection of recurrent prostate cancer in non-prostatectomy patients.

PubMed

Akin-Akintayo, Oladunni; Tade, Funmilayo; Mittal, Pardeep; Moreno, Courtney; Nieh, Peter T; Rossi, Peter; Patil, Dattatraya; Halkar, Raghuveer; Fei, Baowei; Master, Viraj; Jani, Ashesh B; Kitajima, Hiroumi; Osunkoya, Adeboye O; Ormenisan-Gherasim, Claudia; Goodman, Mark M; Schuster, David M

2018-05-01

To investigate the disease detection rate, diagnostic performance and interobserver agreement of fluciclovine ( 18 F) PET-CT and multiparametric magnetic resonance imaging (mpMR) in recurrent prostate cancer. Twenty-four patients with biochemical failure after non-prostatectomy definitive therapy, 16/24 of whom had undergone brachytherapy, underwent fluciclovine PET-CT and mpMR with interpretation by expert readers blinded to patient history, PSA and other imaging results. Reference standard was established via a multidisciplinary truth panel utilizing histology and clinical follow-up (22.9 ± 10.5 months) and emphasizing biochemical control. The truth panel was blinded to investigative imaging results. Diagnostic performance and interobserver agreement (kappa) for the prostate and extraprostatic regions were calculated for each of 2 readers for PET-CT (P1 and P2) and 2 different readers for mpMR (M1 and M2). On a whole body basis, the detection rate for fluciclovine PET-CT was 94.7% (both readers), while it ranged from 31.6-36.8% for mpMR. Kappa for fluciclovine PET-CT was 0.90 in the prostate and 1.0 in the extraprostatic regions. For mpMR, kappa was 0.25 and 0.74, respectively. In the prostate, 22/24 patients met the reference standard with 13 malignant and 9 benign results. Sensitivity, specificity and positive predictive value (PPV) were 100.0%, 11.1% and 61.9%, respectively for both PET readers. For mpMR readers, values ranged from 15.4-38.5% for sensitivity, 55.6-77.8% for specificity and 50.0-55.6% for PPV. For extraprostatic disease determination, 18/24 patients met the reference standard. Sensitivity, specificity and PPV were 87.5%, 90.0% and 87.5%, respectively, for fluciclovine PET-CT, while for mpMR, sensitivity ranged from 50 to 75%, specificity 70-80% and PPV 57-75%. The disease detection rate for fluciclovine PET-CT in non-prostatectomy patients with biochemical failure was 94.7% versus 31.6-36.8% for mpMR. For extraprostatic disease detection, fluciclovine PET-CT had overall better diagnostic performance than mpMR. For the treated prostate, fluciclovine PET-CT had high sensitivity though low specificity for disease detection, while mpMR had higher specificity, though low sensitivity. Interobserver agreement was also higher with fluciclovine PET-CT compared with mpMR. Copyright © 2018 Elsevier B.V. All rights reserved.

Validation study of genes with hypermethylated promoter regions associated with prostate cancer recurrence

PubMed Central

Stott-Miller, Marni; Zhao, Shanshan; Wright, Jonathan L.; Kolb, Suzanne; Bibikova, Marina; Klotzle, Brandy; Ostrander, Elaine A.; Fan, Jian-Bing; Feng, Ziding; Stanford, Janet L.

2014-01-01

Background One challenge in prostate cancer (PCa) is distinguishing indolent from aggressive disease at diagnosis. DNA promoter hypermethylation is a frequent epigenetic event in PCa, but few studies of DNA methylation in relation to features of more aggressive tumors or PCa recurrence have been completed. Methods We used the Infinium® HumanMethylation450 BeadChip to assess DNA methylation in tumor tissue from 407 patients with clinically localized PCa who underwent radical prostatectomy. Recurrence status was determined by follow-up patient surveys, medical record review, and linkage with the SEER registry. The methylation status of 14 genes for which promoter hypermethylation was previously correlated with advanced disease or biochemical recurrence was evaluated. Average methylation level for promoter region CpGs in patients who recurred compared to those with no evidence of recurrence was analyzed. For two genes with differential methylation, time to recurrence was examined. Results During an average follow-up of 11.7 years, 104 (26%) patients recurred. Significant promoter hypermethylation in at least 50% of CpG sites in two genes, ABHD9 and HOXD3, was found in tumors from patients who recurred compared to those without recurrence. Evidence was strongest for HOXD3 (lowest P = 9.46x10−6), with higher average methylation across promoter region CpGs associated with reduced recurrence-free survival (P = 2×10−4). DNA methylation profiles did not differ by recurrence status for the other genes. Conclusions These results validate the association between promoter hypermethylation of ADHB9 and HOXD3 and PCa recurrence. Impact Tumor DNA methylation profiling may help distinguish PCa patients at higher risk for disease recurrence. PMID:24718283

Prognostic value of transformer 2β expression in prostate cancer.

PubMed

Diao, Yan; Wu, Dong; Dai, Zhijun; Kang, Huafeng; Wang, Ziming; Wang, Xijing

2015-01-01

Deregulation of transformer 2β (Tra2β) has been implicated in several cancers. However, the role of Tra2β expression in prostate cancer (PCa) is unclear. Therefore, this study was to investigate the expression of Tra2β in PCa and evaluated its association with clinicopathological variables and prognosis. Thirty paired fresh PCa samples were analyzed for Tra2β expression by Western blot analysis. Immunohistochemistry (IHC) assay was performed in 160 PCa samples after radical prostatectomy and adjacent non-cancerous tissues. Tra2β protein expression was divided into high expression group and low expression group by IHC. We also investigated the association of Tra2β expression with clinical and pathologic parameters. Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the association between Tra2β protein expression and prognosis of PCa patients. Our results showed that Tra2β was significantly upregulated in PCa tissues by western blot and IHC. Our data indicated that high expression of Tra2β was significantly associated with lymph node metastasis (P=0.002), clinical stage (P=0.015), preoperative prostate-specific antigen (P=0.003), Gleason score (P=0.001), and biochemical recurrence (P=0.021). High Tra2β expression was a significant predictor of poor biochemical recurrence free survival and overall survival both in univariate and multivariate analysis. We show that Tra2β was significantly upregulated in PCa patients after radical prostatectomy, and multivariate analysis confirmed Tra2β as an independent prognostic factor.

(68)Ga-PSMA-11 PET/CT: a new technique with high potential for the radiotherapeutic management of prostate cancer patients.

PubMed

Sterzing, Florian; Kratochwil, Clemens; Fiedler, Hannah; Katayama, Sonja; Habl, Gregor; Kopka, Klaus; Afshar-Oromieh, Ali; Debus, Jürgen; Haberkorn, Uwe; Giesel, Frederik L

2016-01-01

Radiotherapy is the main therapeutic approach besides surgery of localized prostate cancer. It relies on risk stratification and exact staging. This report analyses the potential of [(68)Ga]Glu-urea-Lys(Ahx)-HBED-CC ((68)Ga-PSMA-11), a new positron emission tomography (PET) tracer targeting prostate-specific membrane antigen (PSMA) for prostate cancer staging and individualized radiotherapy planning. A cohort of 57 patients with prostate cancer scanned with (68)Ga-PSMA-11 PET/CT for radiotherapy planning was retrospectively reviewed; 15 patients were at initial diagnosis and 42 patients at time of biochemical recurrence. Staging results of conventional imaging, including bone scintigraphy, CT or MRI, were compared with (68)Ga-PSMA ligand PET/CT results and the influence on radiotherapeutic management was quantified. (68)Ga-PSMA ligand PET/CT had a dramatic impact on radiotherapy application in the presented cohort. In 50.8 % of the cases therapy was changed. The presented imaging technique of (68)Ga-PSMA PET/CT could be a key technology for individualized radiotherapy management in prostate cancer.

[High-intensity focused ultrasound (HIFU): our experience in the treatment of prostate cancer relapsing after radiotherapy].

PubMed

Giovanessi, Luca; Peroni, Angelo; Mirabella, Giuseppe; Fugini, Andrea Vismara; Zani, Danilo; Cunico, Sergio Cosciani; Simeone, Claudio

2011-01-01

The aim of the study is to evaluate the safety and efficacy of high-intensity focused ultrasound (HIFU) treatment in patients with local prostate cancer recurrence after radiotherapy. From February 2009 to June 2010, 14 patients with prostate cancer recurrence after radiotherapy were selected for HIFU treatment; all patients had a positive TRUS-guided biopsy and the absence of distant metastases was confirmed by computer tomography, PET choline or bone scintigraphy. We classified all patients in 3 groups using D'Amico's classification: 4 patients high risk (PSA >20 ng/ml - 8≤ Gleason Score≤ 10 - clinical stage≥T2c), 8 patients intermediate risk (10 PSAnadir+1.2ng/ml) or after adjuvant therapy introduction. All complications were recorded. Of the 14 patients selected, 12 patients underwent HIFU treatments; 2 patients were excluded because of rectal strictures induced by radiotherapy. At a mean 13 months' follow-up, biochemical success rate was obtained in 1 of the high risk patients and in 5 of the low and intermediate risk patients; 1 man died for a disease not correlated with prostate cancer recurrence. Complications included urinary tract infection, acute urinary retentions, urethral strictures and light stress incontinence. In our experience salvage HIFU is a safe treatment option for local relapse after radiotherapy; its efficacy depends on a careful patient selection.

A risk-adjusted definition of biochemical recurrence after radical prostatectomy.

PubMed

Morgan, T M; Meng, M V; Cooperberg, M R; Cowan, J E; Weinberg, V; Carroll, P R; Lin, D W

2014-06-01

To determine whether a variable definition of biochemical recurrence (BCR) based on clincopathologic features facilitates early identification of patients likely to suffer from disease progression. The definition of BCR after radical prostatectomy (RP) bears important implications for patient counseling and management; however, there remains a significant debate regarding the appropriate definition. The study cohort consisted of 3619 men who underwent RP for localized prostate cancer from 1989 to 2007, with data abstracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. Patients were stratified into three risk groups according to Cancer of the Prostate Risk Assessment post-Surgical (CAPRA-S) score. Three single threshold PSA cut-points for BCR were evaluated (PSA > or =0.05, > or =0.2 and > or =0.4 ng ml(-1)) as well as a variable cut-point defined by risk group. After reaching the cut-points, patients were followed for further PSA progression. The proportion of patients with BCR differed by cut-point and risk group, ranging from 7 to 37% (low risk), 22 to 58% (intermediate risk) and 60 to 86% (high risk). The positive-predictive value (PPV) for predicting further PSA progression was 49% for the PSA > or =0.05 ng ml(-1), 62% for the PSA > or =0.2 ng ml(-1), 65% for the PSA > or =0.4 ng ml(-1) and 68% for the risk-adjusted definition. Five-year progression-free survival was 39% for the risk-adjusted definition compared with 45-52% for the other definitions of BCR. These data suggest that a variable definition of BCR determined by clinicopathologic risk may improve the identification of early recurrence after RP without increasing the overdiagnosis of BCR. By using a risk-adjusted BCR definition, clinicians can better predict future PSA progression and more appropriately counsel patients regarding salvage therapies.

Evaluation and prognostic significance of ACAT1 as a marker of prostate cancer progression.

PubMed

Saraon, Punit; Trudel, Dominique; Kron, Ken; Dmitromanolakis, Apostolos; Trachtenberg, John; Bapat, Bharati; van der Kwast, Theodorus; Jarvi, Keith A; Diamandis, Eleftherios P

2014-04-01

Prostate cancer is the second leading cause of cancer-related death among men in North America. While a majority of prostate cancer cases remain indolent, subsets of patients develop aggressive cancers, which may lead to death. The current methods of detection include digital rectal examination and the serum PSA test. However, due to lack of specificity, neither of these approaches is able to accurately discriminate between indolent and aggressive cancer, which is why there is a need for additional prognostic factors. Previously, we identified enzymes of the ketogenic pathway, particularly ACAT1, to be elevated in aggressive prostate cancer. In the current study, we assessed the diagnostic and prognostic potential of ACAT1 by analyzing its expression using immunohistochemistry on a tissue microarray consisting of 251 clinically localized prostate cancer patients who have undergone radical prostatectomy. Using quantitative digital imaging software, we found that ACAT1 expression was significantly greater in cancerous cores compared to adjacent benign cores (P < 0.0001), in Gleason score (GS) ≥8 cancers versus GS≤6 cancers (P < 0.0001), GS≥8 cancers versus GS7 cancers (P = 0.001), as well as pT3/pT4 versus pT2 cancers (P = 0.001). In addition, ACAT1 predicted biochemical recurrence in univariate (HR, 1.81, CI = 1.13-2.9, P = 0.0128), and multivariate models (HR, 1.69, CI = 1.01-2.81, P = 0.0431) including pre-operative PSA level, Gleason score and pathological stage. In univariate time-to-recurrence analysis, ACAT1 expression predicted recurrence in ERG negative cases (P = 0.0025), whereas ERG positive cases did not display any differences. Taken together, these findings indicate that ACAT1 expression could serve as a potential prognostic marker in prostate cancer, specifically in differentiating indolent and aggressive forms of cancer. © 2013 Wiley Periodicals, Inc.

High-intensity Focused Ultrasound (HIFU) as salvage therapy for radio-recurrent prostate cancer: predictors of disease response.

PubMed

Dason, Shawn; Wong, Nathan C; Allard, Christopher B; Hoogenes, Jen; Orovan, William; Shayegan, Bobby

2018-01-01

Some men with localized radio-recurrent prostate cancer may benefit from salvage high-intensity focused ultrasound (HIFU). Herein, we describe oncologic outcomes and predictors of disease response after salvage whole gland HIFU from our prospective cohort. Patients with localized radio-recurrent prostate cancer were prospectively enrolled from January 2005 to December 2014. Participants had to meet both biochemical and histological definitions of recurrence. Exclusion criteria included the receipt of prior salvage therapy, presence of metastatic disease, and administration of ADT in the 6-months prior to enrollment. Participants were treated with a single session of whole-gland HIFU ablation with the AblathermTM device (EDAP, France). The primary endpoint was recurrence-free survival (RFS), defined as a composite endpoint of PSA progression (Phoenix criteria), receipt of any further salvage therapy, receipt of ADT, clinical progression, or death. Kaplan-Meier survival analysis was used to determine the primary end-point and stratifications were used to determine the significance of 6 pre-specified predictors of improved RFS (TRUS biopsy grade, number of study entry TRUS biopsy cores positive, palpable disease at study enrollment, pre-HIFU PSA, an undetectable post-HIFU PSA nadir, and receipt of prior hormone therapy). Survival analysis was performed on participants with a minimum of 1-year follow-up. Twenty-four participants were eligible for study inclusion with a median follow-up of 31.0 months. Median PSA at study entry was 4.02ng/ml. Median time to PSA nadir was 3 months after treatment and median post-HIFU PSA nadir was 0.04ng/ ml. Median 2-year and 5-year RFS was 66.3% and 51.6% respectively. Of our 6 pre-specified predictors, an undetectable PSA nadir was the only significant predictor of improved RFS (HR 0.07, 95% CI 0.02-0.29, log-rank P<0.001). One participant underwent an intervention for a urethral stricture. No participants developed osteitis pubis or rectourethral fistulae. Salvage HIFU allows for disease control in selected patients with localized radio-recurrent prostate cancer. An undetectable PSA nadir serves as an early predictor of disease response. Copyright® by the International Brazilian Journal of Urology.

The Roles of the Bone Marrow Microenvironment in Controlling Tumor Dormancy

DTIC Science & Technology

2017-10-01

Prostate cancer patients often have long time periods betweencurative intent surgery or radiation therapy until the time of biochemical recurrence or...incurred by the consequent excision of some benign masses. Radiation triggers EMT Above we reviewed some evidence that chemotherapy and mechanical...tissue disruption give rise to CTC and EMT in surviving cells. Below we review data showing radiation causes CTC and EMT as well.45,46 For a few specific

Robotic-assisted pelvic lymph node dissection for prostate cancer: frequency of nodal metastases and oncological outcomes.

PubMed

Ledezma, Rodrigo A; Negron, Edris; Razmaria, Aria A; Dangle, Pankaj; Eggener, Scott E; Shalhav, Arieh L; Zagaja, Gregory P

2015-11-01

Limited data are available regarding the oncologic efficacy of pelvic lymph node dissection (PLND) performed during robotic-assisted laparoscopic prostatectomy (RALP) for prostate cancer. We aimed to determine the frequency of pelvic lymph node metastasis and oncological outcomes following RALP with PLND in patients who did not receive adjuvant androgen deprivation therapy (ADT). We retrospectively reviewed the records of 1740 consecutive patients who underwent RALP and extended PLND. The primary endpoint was biochemical recurrence (BCR). The estimated BCR probability was obtained using the Kaplan-Meier method. Cox proportional hazard regression models were used to assess for predictors of BCR. One hundred and eight patients (6 %) with positive LNs were identified. The median number of LNs removed was 17 (IQR 11-24), and median follow-up was 26 months (IQR 14-43). Ninety-one (84 %) patients did not receive adjuvant ADT of whom 60 % had BCR with a median time to recurrence of 8 months. The 1- and 3-year BCR-free probability was 42 and 28 %, respectively. Patients with ≤2 LN+ had significantly better biochemical-free estimated probability compared to those with >2 LN+ (p = 0.002). The total number of LN+ (HR = 1.1; 95 % CI 1.01-1.2, p = 0.04) and Gleason 8-10 (HR = 1.96; 95 % CI 1.1-3.4, p = 0.02) were predictors of BCR on multivariate analysis. Among men with positive lymph nodes at time of robotic prostatectomy, those with two or fewer positive nodes and Gleason <8 exhibited favorable biochemical-free survival without adjuvant therapy.

68Ga-PSMA-11 PET/CT Mapping of Prostate Cancer Biochemical Recurrence After Radical Prostatectomy in 270 Patients with a PSA Level of Less Than 1.0 ng/mL: Impact on Salvage Radiotherapy Planning.

PubMed

Calais, Jeremie; Czernin, Johannes; Cao, Minsong; Kishan, Amar U; Hegde, John V; Shaverdian, Narek; Sandler, Kiri; Chu, Fang-I; King, Chris R; Steinberg, Michael L; Rauscher, Isabel; Schmidt-Hegemann, Nina-Sophie; Poeppel, Thorsten; Hetkamp, Philipp; Ceci, Francesco; Herrmann, Ken; Fendler, Wolfgang P; Eiber, Matthias; Nickols, Nicholas G

2018-02-01

Target volume delineations for prostate cancer (PCa) salvage radiotherapy (SRT) after radical prostatectomy are usually drawn in the absence of visibly recurrent disease. 68 Ga-labeled prostate-specific membrane antigen (PSMA-11) PET/CT detects recurrent PCa with sensitivity superior to standard-of-care imaging at serum prostate-specific antigen (PSA) values low enough to affect target volume delineations for routine SRT. Our objective was to map the recurrence pattern of PCa early biochemical recurrence (BCR) after radical prostatectomy with 68 Ga-PSMA-11 PET/CT in patients with serum PSA levels of less than 1 ng/mL, determine how often consensus clinical target volumes (CTVs) based on the Radiation Therapy Oncology Group (RTOG) guidelines cover 68 Ga-PSMA-11 PET/CT-defined disease, and assess the potential impact of 68 Ga-PSMA-11 PET/CT on SRT. Methods: This was a post hoc analysis of an intention-to-treat population of 270 patients who underwent 68 Ga-PSMA-11 PET/CT at 4 institutions for BCR after prostatectomy without prior radiotherapy at a PSA level of less than 1 ng/mL. RTOG consensus CTVs that included both the prostate bed and the pelvic lymph nodes were contoured on the CT dataset of the PET/CT image by a radiation oncologist masked to the PET component. 68 Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. 68 Ga-PSMA-11-positive lesions not covered by planning volumes based on the consensus CTVs were considered to have a potential major impact on treatment planning. Results: The median PSA level at the time of 68 Ga-PSMA-11 PET/CT was 0.48 ng/mL (range, 0.03-1 ng/mL). One hundred thirty-two of 270 patients (49%) had a positive 68 Ga-PSMA-11 PET/CT result. Fifty-two of 270 (19%) had at least one PSMA-11-positive lesion not covered by the consensus CTVs. Thirty-three of 270 (12%) had extrapelvic PSMA-11-positive lesions, and 19 of 270 (7%) had PSMA-11-positive lesions within the pelvis but not covered by the consensus CTVs. The 2 most common 68 Ga-PSMA-11-positive lesion locations outside the consensus CTVs were bone (23/52, 44%) and perirectal lymph nodes (16/52, 31%). Conclusion: Post hoc analysis of 68 Ga-PSMA-11 PET/CT implied a major impact on SRT planning in 52 of 270 patients (19%) with PCa early BCR (PSA < 1.0 ng/mL). This finding justifies a randomized imaging trial of SRT with or without 68 Ga-PSMA-11 PET/CT investigating its potential benefit on clinical outcome. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

AXIN2 expression predicts prostate cancer recurrence and regulates invasion and tumor growth.

PubMed

Hu, Brian R; Fairey, Adrian S; Madhav, Anisha; Yang, Dongyun; Li, Meng; Groshen, Susan; Stephens, Craig; Kim, Philip H; Virk, Navneet; Wang, Lina; Martin, Sue Ellen; Erho, Nicholas; Davicioni, Elai; Jenkins, Robert B; Den, Robert B; Xu, Tong; Xu, Yucheng; Gill, Inderbir S; Quinn, David I; Goldkorn, Amir

2016-05-01

Treatment of prostate cancer (PCa) may be improved by identifying biological mechanisms of tumor growth that directly impact clinical disease progression. We investigated whether genes associated with a highly tumorigenic, drug resistant, progenitor phenotype impact PCa biology and recurrence. Radical prostatectomy (RP) specimens (±disease recurrence, N = 276) were analyzed by qRT-PCR to quantify expression of genes associated with self-renewal, drug resistance, and tumorigenicity in prior studies. Associations between gene expression and PCa recurrence were confirmed by bootstrap internal validation and by external validation in independent cohorts (total N = 675) and in silico. siRNA knockdown and lentiviral overexpression were used to determine the effect of gene expression on PCa invasion, proliferation, and tumor growth. Four candidate genes were differentially expressed in PCa recurrence. Of these, low AXIN2 expression was internally validated in the discovery cohort. Validation in external cohorts and in silico demonstrated that low AXIN2 was independently associated with more aggressive PCa, biochemical recurrence, and metastasis-free survival after RP. Functionally, siRNA-mediated depletion of AXIN2 significantly increased invasiveness, proliferation, and tumor growth. Conversely, ectopic overexpression of AXIN2 significantly reduced invasiveness, proliferation, and tumor growth. Low AXIN2 expression was associated with PCa recurrence after RP in our test population as well as in external validation cohorts, and its expression levels in PCa cells significantly impacted invasiveness, proliferation, and tumor growth. Given these novel roles, further study of AXIN2 in PCa may yield promising new predictive and therapeutic strategies. © 2016 Wiley Periodicals, Inc.

Canary TMA — EDRN Public Portal

Cancer.gov

This protocol describes a multi-center, retrospective, case-cohort tissue microarray (TMA) study to evaluate tissue biomarkers for their ability to predict recurrent prostate cancer at the time of radical prostatectomy (RP). Candidate biomarkers will be assessed by performing tissue localization studies on TMAs containing recurrent prostate cancer and non-recurrent prostate cancer. De-identified data will be transferred to a central repository for statistical analysis. Participating institutions will use a variation of case-cohort sampling to randomly select a subset of patients from a retrospectively constructed RP cohort and/or perform selected assays on the cohort. The study endpoint is time to recurrence; of primary interest is five year recurrence free survival. Recurrent prostate cancer is defined by 1) a single serum prostate-specific antigen (PSA) level greater than 0.2 ng/mL after RP and/or 2) receipt of salvage or secondary therapy after RP and/or 3) clinical or radiological evidence of metastatic disease. Non-recurrent prostate cancer is defined as disease with no evidence of recurrence.

Cyclin K dependent regulation of Aurora B affects apoptosis and proliferation by induction of mitotic catastrophe in prostate cancer.

PubMed

Schecher, Sabrina; Walter, Britta; Falkenstein, Michael; Macher-Goeppinger, Stephan; Stenzel, Philipp; Krümpelmann, Kristina; Hadaschik, Boris; Perner, Sven; Kristiansen, Glen; Duensing, Stefan; Roth, Wilfried; Tagscherer, Katrin E

2017-10-15

Cyclin K plays a critical role in transcriptional regulation as well as cell development. However, the role of Cyclin K in prostate cancer is unknown. Here, we describe the impact of Cyclin K on prostate cancer cells and examine the clinical relevance of Cyclin K as a biomarker for patients with prostate cancer. We show that Cyclin K depletion in prostate cancer cells induces apoptosis and inhibits proliferation accompanied by an accumulation of cells in the G2/M phase. Moreover, knockdown of Cyclin K causes mitotic catastrophe displayed by multinucleation and spindle multipolarity. Furthermore, we demonstrate a Cyclin K dependent regulation of the mitotic kinase Aurora B and provide evidence for an Aurora B dependent induction of mitotic catastrophe. In addition, we show that Cyclin K expression is associated with poor biochemical recurrence-free survival in patients with prostate cancer treated with an adjuvant therapy. In conclusion, targeting Cyclin K represents a novel, promising anti-cancer strategy to induce cell cycle arrest and apoptotic cell death through induction of mitotic catastrophe in prostate cancer cells. Moreover, our results indicate that Cyclin K is a putative predictive biomarker for clinical outcome and therapy response for patients with prostate cancer. © 2017 UICC.

18F-Fluorocholine PET/CT Complementing the Role of Dynamic Contrast-Enhanced MRI for Providing Comprehensive Diagnostic Workup in Prostate Cancer Patients With Suspected Relapse Following Radical Prostatectomy.

PubMed

Vadi, Shelvin Kumar; Singh, Baljinder; Basher, Rajender K; Watts, Ankit; Sood, Ashwani K; Lal, Anupam; Kakkar, Nandita; Singh, S K

2017-08-01

The aim of this study was to compare the diagnostic performance of F-fluorocholine (FCH) PET/CT and dynamic contrast-enhanced MRI (DCE-MRI) of pelvis in restaging prostate cancer (PC) patients with biochemical recurrence (BCR) following radical prostatectomy (RP). Twenty PC patients who had undergone RP and had BCR were recruited in this study. All the patients underwent whole-body FCH PET/CT and DCE-MRI of the pelvis. An overall pattern of recurrent disease was analyzed, and diagnostic accuracy for the detection of pelvic disease recurrence by the 2 modalities was evaluated by taking histopathologic analysis as the criterion standard. The whole-body FCH PET/CT images were also analyzed separately for the presence of any extra lesion(s). The initial mean Gleason score was 6.3 ± 1.53 (range, 4-9). The mean prostate-specific antigen levels at the time of relapse were 1.9 ± 2.87 ng/mL (range, 0.24-13.2 ng/mL). MRI findings were positive for primary tumor recurrence in the prostate bed in 6 patients (6/20 [30.0%]), pelvic lymph node metastases in 4 patients (4/20 [20.0%]), and for pelvic skeletal metastases in 2 patients (2/20 [10.0%]), respectively. On the other hand, FCH PET/CT results were positive in the corresponding sites in 7 (7/20 [35.0%]), 9 (9/20 [45.0%]), and 2 patients (2/20 [10.0%]), respectively. F-fluorocholine PET/CT and MRI showed comparable results in terms of sensitivity, specificity, and positive and negative predictive values for PC characterization. The whole-body FCH PET/CT was found to be useful in identifying unknown distant metastases in a significant proportion of patients. The correlative whole-body FCH PET/CT and pelvic DCE-MRI offer a complementary and comprehensive diagnostic workup for better management of PC patients with BCR following RP.

Heterogeneous clinicopathological features of intraductal carcinoma of the prostate: a comparison between "precursor-like" and "regular type" lesions.

PubMed

Miyai, Kosuke; Divatia, Mukul K; Shen, Steven S; Miles, Brian J; Ayala, Alberto G; Ro, Jae Y

2014-01-01

Intraductal carcinoma of the prostate (IDC-P) has been described as a lesion associated with intraductal spread of invasive carcinoma and consequently aggressive disease. However, there are a few reported cases of pure IDC-P without an associated invasive component, strongly suggesting that this subset of IDC-P may represent a precursor lesion. We compared the clinicopathological features between the morphologically "regular type" IDC-P and "precursor-like" IDC-P. IDC-P was defined as follows; 1) solid/dense cribriform lesions or 2) loose cribriform/micropapillary lesions with prominent nuclear pleomorphism and/or non-focal comedonecrosis. We defined precursor-like IDC-P as follows; 1) IDC-P without adjoining invasive adenocarcinoma but carcinoma present distant from the IDC-P or 2) IDC-P having adjoining invasive microcarcinoma (less than 0.05 ml) and showing a morphologic transition from high-grade prostatic intraepithelial neoplasia (HGPIN) to the IDC-P. IDC-P lacking the features of precursor-like IDC-P was categorized as regular type IDC-P. Of 901 radical prostatectomies performed at our hospital, 141 and 14 showed regular type IDC-P and precursor-like IDC-P in whole-mounted specimens, respectively. Regular type IDC-P cases had significantly higher Gleason score, more frequent extraprostatic extension and seminal vesicle invasion, more advanced pathological T stage, and lower 5-year biochemical recurrence-free rate than precursor-like IDC-P cases. Multivariate analysis revealed nodal metastasis and the presence of regular type IDC-P as independent predictors for biochemical recurrence. Our data suggest that IDC-P may be heterogeneous with variable clinicopathological features. We also suggest that not all IDC-P cases represent intraductal spread of pre-existing invasive cancer, and a subset of IDC-P may be a precursor lesion.

A Diet, Physical Activity, and Stress Reduction Intervention in Men with Rising Prostate-Specific Antigen (PSA) after Treatment for Prostate Cancer

PubMed Central

Hébert, James R.; Hurley, Thomas G.; Harmon, Brook E.; Heiney, Sue; Hebert, Christine J.; Steck, Susan E.

2011-01-01

Background Nearly 35% of men treated for prostate cancer (PrCA) will experience biochemically defined recurrence, noted by a rise in PSA, within ten years of definitive therapy. Diet, physical activity, and stress reduction may affect tumor promotion and disease progression. Methods A randomized trial of an intensive diet, physical activity, and meditation intervention was conducted in men with rising post-treatment PSA after definitive treatment for PrCA. Intention-to-treat methods were used to compare usual care to the intervention in 47 men with complete data. Signal detection methods were used to identify dietary factors associated with PSA change. Results The intervention and control groups did not differ statistically on any demographic or disease-related factor. Although the intervention group experienced decreases of 39% in intakes of saturated fatty acid (SFA as percent of total calories) (p<0.0001) and 12% in total energy intake (218 kcal/day p<0.05)], no difference in PSA change was observed by intervention status. Signal detection methods indicated that in men increasing their consumption of fruit, 56% experienced no rise in PSA (vs. 29% in men who did not increase their fruit intake). Among men who increased fruit and fiber intakes, PSA increased in 83% of participants who also increased saturated fatty acid intake (vs. 44% in participants who decreased or maintained saturated fatty acid intake). Conclusion Results are discussed in the context of conventional treatment strategies that were more aggressive when this study was being conducted in the mid-2000s. Positive health changes in a number of lifestyle parameters were observed with the intervention, and both increased fruit and reduced saturated fat intakes were associated with maintaining PSA levels in men with biochemically recurrent disease. PMID:22018935

Neoadjuvant luteinizing-hormone-releasing hormone agonist plus low-dose estramustine phosphate improves prostate-specific antigen-free survival in high-risk prostate cancer patients: a propensity score-matched analysis.

PubMed

Koie, Takuya; Mitsuzuka, Koji; Yoneyama, Takahiro; Narita, Shintaro; Kawamura, Sadafumi; Kaiho, Yasuhiro; Tsuchiya, Norihiko; Tochigi, Tatsuo; Habuchi, Tomonori; Arai, Yoichi; Ohyama, Chikara; Yoneyama, Tohru; Tobisawa, Yuki

2015-10-01

The optimal treatment for high-risk prostate cancer (Pca) remains to be established. We previously reported favorable biochemical recurrence-free survival (BRFS) in high-risk Pca patients treated with a neoadjuvant therapy comprising a luteinizing-hormone-releasing hormone (LHRH) agonist plus low dose estramustine phosphate (EMP) (LHRH+EMP) followed by radical prostatectomy (RP). In the present study, we used a retrospective design via propensity score matching to elucidate the clinical benefit of neoadjuvant LHRH+EMP for high-risk Pca. The Michinoku Urological Cancer Study Group database contained data for 1,268 consecutive Pca patients treated with RP alone at 4 institutions between April 2000 and March 2011 (RP alone group). In the RP alone group, we identified 386 high-risk Pca patients. The neoadjuvant LHRH+EMP group included 274 patients with high-risk Pca treated between September 2005 and November 2013 at Hirosaki University. Neoadjuvant LHRH+EMP therapy included LHRH and EMP administration at a dose of 280 mg/day for 6 months before RP. The outcome measures were overall survival (OS) and BRFS. The propensity score-matched analysis indicated 210 matched pairs from both groups. The 5-year BRFS rates were 90.4 and 65.8 % for the neoadjuvant LHRH+EMP and RP alone groups, respectively (P < 0.0001). The 5-year OS rates were 100 and 96.1 % for the neoadjuvant LHRH+EMP and RP alone groups, respectively (P = 0.110). Although the present study was not randomized, neoadjuvant LHRH+EMP therapy followed by RP appeared to reduce the risk of biochemical recurrence. A prospective randomized study is warranted to determine the clinical implications of the neoadjuvant therapy described here.

CDO1 promoter methylation is associated with gene silencing and is a prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients.

PubMed

Meller, Sebastian; Zipfel, Lisa; Gevensleben, Heidrun; Dietrich, Jörn; Ellinger, Jörg; Majores, Michael; Stein, Johannes; Sailer, Verena; Jung, Maria; Kristiansen, Glen; Dietrich, Dimo

2016-12-01

Molecular biomarkers may facilitate the distinction between aggressive and clinically insignificant prostate cancer (PCa), thereby potentially aiding individualized treatment. We analyzed cysteine dioxygenase 1 (CDO1) promoter methylation and mRNA expression in order to evaluate its potential as prognostic biomarker. CDO1 methylation and mRNA expression were determined in cell lines and formalin-fixed paraffin-embedded prostatectomy specimens from a first cohort of 300 PCa patients using methylation-specific qPCR and qRT-PCR. Univariate and multivariate Cox proportional hazards and Kaplan-Meier analyses were performed to evaluate biochemical recurrence (BCR)-free survival. Results were confirmed in an independent second cohort comprising 498 PCa cases. Methylation and mRNA expression data from the second cohort were generated by The Cancer Genome Atlas (TCGA) Research Network by means of Infinium HumanMethylation450 BeadChip and RNASeq. CDO1 was hypermethylated in PCa compared to normal adjacent tissues and benign prostatic hyperplasia (P < 0.001) and was associated with reduced gene expression (ρ = -0.91, P = 0.005). Using two different methodologies for methylation quantification, high CDO1 methylation as continuous variable was associated with BCR in univariate analysis (first cohort: HR = 1.02, P = 0.002, 95% CI [1.01-1.03]; second cohort: HR = 1.02, P = 0.032, 95% CI [1.00-1.03]) but failed to reach statistical significance in multivariate analysis. CDO1 promoter methylation is involved in gene regulation and is a potential prognostic biomarker for BCR-free survival in PCa patients following radical prostatectomy. Further studies are needed to validate CDO1 methylation assays and to evaluate the clinical utility of CDO1 methylation for the management of PCa.

11C choline PET guided salvage radiotherapy with volumetric modulation arc therapy and hypofractionation for recurrent prostate cancer after HIFU failure: preliminary results of tolerability and acute toxicity.

PubMed

Alongi, Filippo; Liardo, Rocco L E; Iftode, Cristina; Lopci, Egesta; Villa, Elisa; Comito, Tiziana; Tozzi, Angelo; Navarria, Pierina; Ascolese, Anna M; Mancosu, Pietro; Tomatis, Stefano; Bellorofonte, Carlo; Arturo, Chiti; Scorsetti, Marta

2014-10-01

The purpose of this work was to evaluate tolerance, feasibility and acute toxicity in patients undergoing salvage radiotherapy after high-intensity focused ultrasound (HIFU) failure. From 2005 to 2011 a total of 15 patients were treated with HIFU as primary radical treatment. Between July 2011 and February 2013, all 15 patients presented biochemical relapse after HIFU and 11C choline PET documenting intrapostatic-only failure. Salvage EBRT was performed with moderate hypofractionation schedule in 28 fractions with volumetric modulation arc therapy (VMAT). Genito-urinary (GU) and rectal and bowel toxicity were scored by common terminology criteria for adverse events version 4 (CTCAE V.4) scale. Biochemical response was assessed by ASTRO Phoenix criteria. Median age of patients was 67 years (range: 53-85). The median Gleason score was 7 (range: 6-9). The median prostate specific antigen (PSA) at the time of biochemical relapse after HIFU was 5.2 ng/mL (range: 2-64.2). Seven of the 15 patients received androgen deprivation therapy (ADT) started after HIFU failure, interrupted before 11C choline PET and radiotherapy. Median prescribed dose was 71.4 Gy (range: 71.4-74.2 Gy) in 28 fractions. No radiation related major upper gastrointestinal (GI), rectal and GU toxicity were experienced. GU, acute grade 1 and grade 2 toxicities were recorded in 7/15 and 4/15 respectively; bowel acute grade 1 and grade 2 toxicities in 4/15 and 1/15; rectal acute grade 1 and grade 2 toxicities in 3/15 and 2/15 respectively. No grade 3 or greater acute or late toxicities occurred. Biochemical control was assessed in 12/15 (80%) patients. With a median follow up of 12 months, three out of 15 patients, with biochemical relapse, showed lymph-nodal recurrence. Our early clinical results and biochemical data confirm the feasibility and show a good tolerance of the 11C choline PET guided salvage radiation therapy after HIFU failure. The findings of low acute toxicity is encouraging, but longer follow-up is needed to assess late toxicity and definitive outcomes.

Patients' perceptions and attitudes on recurrent prostate cancer and hormone therapy: Qualitative comparison between decision-aid and control groups.

PubMed

Gorawara-Bhat, Rita; O'Muircheartaigh, Siobhan; Mohile, Supriya; Dale, William

2017-09-01

To compare patients' attitudes towards recurrent prostate cancer (PCa) and starting hormone therapy (HT) treatment in two groups-Decision-Aid (DA) (intervention) and Standard-of-care (SoC) (Control). The present research was conducted at three academic clinics-two in the Midwest and one in the Northeast U.S. Patients with biochemical recurrence of PCa (n=26) and follow-up oncology visits meeting inclusion criteria were randomized to either the SoC or DA intervention group prior to their consultation. Analysts were blinded to group assignment. Semi-structured phone interviews with patients were conducted 1-week post consultation. Interviews were audio-taped and transcribed. Qualitative analytic techniques were used to extract salient themes and conduct a comparative analysis of the two groups. Four salient themes emerged-1) knowledge acquisition, 2) decision-making style, 3) decision-making about timing of HT, and 4) anxiety-coping mechanisms. A comparative analysis showed that patients receiving the DA intervention had a better comprehension of Prostate-specific antigen (PSA), an improved understanding of HT treatment implications, an external locus-of-control, participation in shared decision-making and, support-seeking for anxiety reduction. In contrast, SoC patients displayed worse comprehension of PSA testing and HT treatment implications, internal locus-of-control, unilateral involvement in knowledge-seeking and decision-making, and no support-seeking for anxiety-coping. The DA was more effective than the SoC group in helping PCa patients understand the full implications of PSA testing and treatment; motivating shared decision-making, and support-seeking for anxiety relief. DA DVD interventions can be a useful patient education tool for bringing higher quality decision-making to prostate cancer care. Copyright © 2017 Elsevier Ltd. All rights reserved.

Methylation profiling identified novel differentially methylated markers including OPCML and FLRT2 in prostate cancer.

PubMed

Wu, Yu; Davison, Jerry; Qu, Xiaoyu; Morrissey, Colm; Storer, Barry; Brown, Lisha; Vessella, Robert; Nelson, Peter; Fang, Min

2016-04-02

To develop new methods to distinguish indolent from aggressive prostate cancers (PCa), we utilized comprehensive high-throughput array-based relative methylation (CHARM) assay to identify differentially methylated regions (DMRs) throughout the genome, including both CpG island (CGI) and non-CGI regions in PCa patients based on Gleason grade. Initially, 26 samples, including 8 each of low [Gleason score (GS) 6] and high (GS ≥7) grade PCa samples and 10 matched normal prostate tissues, were analyzed as a discovery cohort. We identified 3,567 DMRs between normal and cancer tissues, and 913 DMRs distinguishing low from high-grade cancers. Most of these DMRs were located at CGI shores. The top 5 candidate DMRs from the low vs. high Gleason comparison, including OPCML, ELAVL2, EXT1, IRX5, and FLRT2, were validated by pyrosequencing using the discovery cohort. OPCML and FLRT2 were further validated in an independent cohort consisting of 20 low-Gleason and 33 high-Gleason tissues. We then compared patients with biochemical recurrence (n=70) vs. those without (n=86) in a third cohort, and they showed no difference in methylation at these DMR loci. When GS 3+4 cases and GS 4+3 cases were compared, OPCML-DMR methylation showed a trend of lower methylation in the recurrence group (n=30) than in the no-recurrence (n=52) group. We conclude that whole-genome methylation profiling with CHARM revealed distinct patterns of differential DNA methylation between normal prostate and PCa tissues, as well as between different risk groups of PCa as defined by Gleason scores. A panel of selected DMRs may serve as novel surrogate biomarkers for Gleason score in PCa.

[Testosterone replacement therapy for late-onset hypogonadism after radical prostatectomy: a case report].

PubMed

Nakano, Kosuke; Kiuchi, Hiroshi; Miyagawa, Yasushi; Tsujimura, Akira; Nonomura, Norio

2014-08-01

A 53-year-old man presented to our hospital with a few-month history of fatigue and anorexia. His aging male's symptoms (AMS) score was 57, and the free testosterone value was low (6.5 pg/ml). He was diagnosed with severe late-onset hypogonadism indicative of androgen replacement therapy (ART). His serum prostate specific antigen was 8.7 ng/ml, and pelvic magnetic resonance imaging showed a low intensity area in the peripheral zone of the prostate. A systematic 10-core prostate biopsy revealed one core of adenocarcinoma with a Gleason score of 3 + 3=6. Imaging examination revealed organ-confined prostate cancer that was cT2aN0M0. Given his desire for ART for the treatment of hypogonadism, the patient underwent open radical prostatectomy. Pathologic examination demonstrated prostate adenocarcinoma that was pT2aN0, and Gleason score of 3 + 3=6. After confirming that the prostate specific antigen value was under 0.01 ng/ml for three years after prostatectomy, the patient received 125 mg methyltestosterone monthly. His hypogonadism-related symptoms diminished and AMS score dropped to 48. During a three-year follow-up of ART, no biochemical recurrence was found.

99m Tc-MIP-1404-SPECT/CT for the detection of PSMA-positive lesions in 225 patients with biochemical recurrence of prostate cancer.

PubMed

Schmidkonz, Christian; Hollweg, Claudia; Beck, Michael; Reinfelder, Julia; Goetz, Theresa I; Sanders, James C; Schmidt, Daniela; Prante, Olaf; Bäuerle, Tobias; Cavallaro, Alexander; Uder, Michael; Wullich, Bernd; Goebell, Peter; Kuwert, Torsten; Ritt, Philipp

2018-01-01

99m Tc-MIP-1404 (Progenics Pharmaceuticals, Inc., New York, NY) is a novel, SPECT-compatible 99m Tc-labeled PSMA inhibitor for the detection of prostate cancer. We present results of its clinical use in a cohort of 225 men with histologically confirmed prostate cancer referred for workup of biochemical relapse. From April 2013 to April 2017, 99m Tc-MIP1404-scintigraphy was performed in 225 patients for workup of PSA biochemical relapse of prostate cancer. Whole-body planar and SPECT/CT images of the lower abdomen and thorax were obtained 3-4 h p.i. of 710 ± 64 MBq 99m Tc-MIP-1404. Images were visually analyzed for presence and location of abnormal uptake. In addition, quantitative analysis of the SPECT/CT data was carried out on a subset of 125 patients. Follow-up reports of subsequent therapeutic interventions were available for 59% (139) of all patients. Tracer-positive lesions were detected in 77% (174/225) of all patients. Detections occurred at the area of local recurrence in the prostate in 25% of patients (or a total of 56), with metastases in lymph nodes in 47% (105), bone in 27% (60), lung in 5% (12), and other locations in 2% (4) of patients. Detection rates were 90% at PSA levels ≥2 ng/mL and 54% below that threshold. Lesional SUVmax values were, on average, 32.2 ± 29.6 (0.8-142.2), and tumor-to-normal ratios 146.6 ± 160.5 (1.9-1482.4). The PSA level correlated significantly with total uptake of MIP-1404 in tumors (P < 0.001). Furthermore, total tumor uptake was significantly higher in patients with Gleason scores ≥8 compared to those with Gleason scores ≤7 (P < 0.05). In patients with androgen deprivation therapy, the detection rate was significantly higher compared to patients without androgen deprivation therapy (86% vs 71%, P < 0.001). Based on 99m Tc-MIP-1404-imaging and other information, an interdisciplinary tumor board review recommended changes to treatment plans in 74% (104/139) of those patients for whom the necessary documentation was available. SPECT/CT with 99m Tc-labeled MIP-1404 has a high probability in detecting PSMA-positive lesions in patients with elevated PSA. Statistical analysis disclosed significant relationship between quantitative 99m Tc-MIP-1404 uptake, PSA level, and Gleason score. © 2017 Wiley Periodicals, Inc.

Current Status of Prostate-Specific Membrane Antigen Targeting in Nuclear Medicine: Clinical Translation of Chelator Containing Prostate-Specific Membrane Antigen Ligands Into Diagnostics and Therapy for Prostate Cancer.

PubMed

Kratochwil, Clemens; Afshar-Oromieh, Ali; Kopka, Klaus; Haberkorn, Uwe; Giesel, Frederik L

2016-09-01

The prostate-specific membrane antigen (PSMA) is expressed by approximately 90% of prostate carcinomas. The expression correlates with unfavorable prognostic factors, such as a high Gleason score, infiltrative growth, metastasis, and hormone-independence. The high specificity, especially in the undifferentiated stage, makes it an excellent target for diagnosis and therapy. Therefore, antibodies and small molecule inhibitors have been developed for imaging and therapy. In 2011 PSMA-11, a ligand that consists of the Glu-urea-motif and the chelator HBED-CC, which can be exclusively radiolabeled with (68)Ga for PET imaging, presented the clinical breakthrough for prostate cancer diagnostics. In two large diagnostic studies (n = 319 and n = 248) PET/CT with PSMA-11 successfully localized the recurrent tumor in approximately 90% of patients with biochemical relapse. Integrating PSMA-PET/CT into the planning phase of radiotherapy, the treatment concept is changed in 30%-50% of the patients. The combination of the Glu-urea-motif with DOTA, which can be labeled with several diagnostic and therapeutic radionuclides, opened new avenues for therapeutic usage of the small-molecule PSMA ligands. In the beginning of 2016, there are four confirmative reports (n = 19, n = 24, n = 30, and n = 56) from four different centers reporting a PSA response in approximately 70% of patients treated with (177)Lu-labeled PSMA ligands. In conclusion, the data available up to now indicate a widespread use of PSMA ligands for diagnostic applications with respect to staging, detection of recurrence, or metastases in patients with rising tumor markers and for therapy in case of failure of guideline-compliant treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Stromal expression of VEGF-A and VEGFR-2 in prostate tissue is associated with biochemical and clinical recurrence after radical prostatectomy.

PubMed

Nordby, Yngve; Andersen, Sigve; Richardsen, Elin; Ness, Nora; Al-Saad, Samer; Melbø-Jørgensen, Christian; Patel, Hiten R H; Dønnem, Tom; Busund, Lill-Tove; Bremnes, Roy M

2015-11-01

There is probably significant overtreatment of patients with prostate cancer due to a lack of sufficient diagnostic tools to predict aggressive disease. Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are potent mediators of angiogenesis and tumor proliferation, but have been examined to a limited extent in large prostate cancer studies. Meanwhile, recent promising results on VEGFR-2 inhibition have highlighted their importance, leading to the need for further investigations regarding their expression and prognostic impact. Using tissue microarray and immunohistochemistry, the expression of VEGFs (VEGF-A and VEGF-C) and their receptors (VEGFR-2 and VEGFR-3) were measured in neoplastic tissue and corresponding stroma from radical prostatectomy specimens in 535 Norwegian patients. Their expression was evaluated semiquantatively and associations with event-free survival were calculated. High expression of VEGFR-2 in either stroma or epithelium was independently associated with a higher incidence of prostate cancer relapse (HR = 4.56, P = 0.038). A high combined expression of either VEGF-A, VEGFR-2 or both in stroma was independently associated with a higher incidence of biochemical failure (HR = 1.77, P = 0.011). This large study highlights the prognostic importance of VEGF-A and VEGFR-2 stromal expression. Analyses of these biomarkers may help distinguish which patients will benefit from radical treatment. Together with previous studies showing efficiency of targeting VEGFR-2 in prostate cancer, this study highlights its potential as a target for therapy, and may aid in future selection of prostate cancer patients for novel anti-angiogenic treatment. © 2015 Wiley Periodicals, Inc.

Prognostic significance of 5-year PSA value for predicting prostate cancer recurrence after brachytherapy alone and combined with hormonal therapy and/or external beam radiotherapy.

PubMed

Stock, Richard G; Klein, Thomas J; Cesaretti, Jamie A; Stone, Nelson N

2009-07-01

To analyze the prognosis and outcomes of patients who remain free of biochemical failure during the first 5 years after treatment. Between 1991 and 2002, 742 patients with prostate cancer were treated with brachytherapy alone (n = 306), brachytherapy and hormonal therapy (n = 212), or combined implantation and external beam radiotherapy (with or without hormonal therapy; n = 224). These patients were free of biochemical failure (American Society for Therapeutic Radiology and Oncology [ASTRO] definition) during the first 5 post-treatment years and had a documented 5-year prostate-specific antigen (PSA) value. The median follow-up was 6.93 years. The actuarial 10-year freedom from PSA failure rate was 97% using the ASTRO definition and 95% using the Phoenix definition. The median 5-year PSA level was 0.03 ng/mL (range, 0-3.6). The 5-year PSA value was 0.01-0.10 in 31.1%, >0.10-0.2 in 10.2%, >0.2-0.5 in 7.82%, and >0.5 in 3.10%. The 5-year PSA value had prognostic significance, with a PSA value of or=0.2 ng/mL (n = 81; p < .0001). The treatment regimen had no effect on biochemical failure. None of the 742 patients in this study developed metastatic disease or died of prostate cancer. The results of this study have shown that the prognosis for patients treated with brachytherapy and who remain biochemically free of disease for >or=5 years is excellent and none developed metastatic disease during the first 10 years after treatment. The 5-year PSA value is prognostic, and patients with a PSA value <0.2 ng/mL are unlikely to develop subsequent biochemical relapse.

18F-choline PET/MRI in suspected recurrence of prostate carcinoma.

PubMed

Riola-Parada, C; Carreras-Delgado, J L; Pérez-Dueñas, V; Garcerant-Tafur, M; García-Cañamaque, L

2018-05-21

To evaluate the usefulness of simultaneous 18 F-choline PET/MRI in the suspicion of prostate cancer recurrence and to relate 18 F-choline PET/MRI detection rate with analytical and pathological variables. 27 patients with prostate cancer who received local therapy as primary treatment underwent a 18 F-choline PET/MRI due to suspicion of recurrence (persistently rising serum PSA level). 18 F-choline PET/MRI findings were validated by anatomopathological analysis, other imaging tests or by biochemical response to oncological treatment. 18 F-choline PET/MRI detected disease in 15 of 27 patients (detection rate 55.56%). 4 (15%) presented exclusively local recurrence, 5 (18%) lymph node metastases and 7 (26%) bone metastases. Mean PSA (PSA med ) at study time was 2.94ng/mL (range 0.18-10ng/mL). PSA med in patients with positive PET/MRI was 3.70ng/mL (range 0.24-10ng/mL), higher than in patients with negative PET/MRI, PSA med 1.97ng/mL (range 0.18-4.38ng/mL), although without statistically significant differences. Gleason score at diagnosis in patients with a positive study was 7.33 (range 6-9) and in patients with a negative study was 7 (range 6-9), without statistically significant differences. 18 F-choline PET/MRI detection rate was considerable despite the relatively low PSA values in our sample. The influence of Gleason score and PSA level on 18 F-choline PET/MRI detection rate was not statistically significant. Copyright © 2018 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.

Intensity-modulated salvage radiotherapy with simultaneous integrated boost for local recurrence of prostate carcinoma: a pilot study on the place of PET-choline for guiding target volume delineation.

PubMed

Wahart, Aurélien; Guy, Jean-Baptiste; Vallard, Alexis; Geissler, Benjamin; Ben Mrad, Majed; Falk, Alexander T; Prevot, Nathalie; de Laroche, Guy; Rancoule, Chloé; Chargari, Cyrus; Magné, Nicolas

2016-01-01

The aim of this study was to report the first cases of salvage radiotherapy (RT) using the intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) targeted on choline positron emission tomography (PET) uptake in a local recurrent prostate cancer, after a radical prostatectomy. Four patients received salvage irradiation for biochemical relapse that occurred after the initial radical prostatectomy. The relapse occurred from 10 months to 6 years with PSA levels ranging from 2.35 to 4.86 ng ml(-1). For each patient, an (18)F-choline PET-CT showed a focal choline uptake in prostatic fossa, with standardized uptake value calculated on the basis of predicted lean body mass (SUL) max of 3.3-6.8. No involved lymph node or distant metastases were diagnosed. IMRT doses were of 62.7 Gy (1.9 Gy/fraction, 33 fractions), with a SIB of 69.3 Gy (2.1 Gy/fraction, 33 fractions) to a PET-guided target volume. Acute toxicities were limited. We observed no gastrointestinal toxicity ≥grade 2 and only one grade 2 genitourinary toxicity. At 1-month follow-up evaluation, no complication and a decrease in PSA level (6.8-43.8% of the pre-therapeutic level) were reported. After 4 months, a decrease in PSA level was obtained for all the patients, ranging from 30% to 70%. At a median follow-up of 15 months, PSA level was controlled for all the patients, but one of them experienced a distant lymph node recurrence. Salvage irradiation to the prostate bed with SIB guided by PET-CT is feasible, with biological efficacy and no major acute toxicity. IMRT with PET-oriented SIB for salvage treatment of prostate cancer is possible, without major acute toxicity.

Beyond D'Amico risk classes for predicting recurrence after external beam radiotherapy for prostate cancer: the Candiolo classifier.

PubMed

Gabriele, Domenico; Jereczek-Fossa, Barbara A; Krengli, Marco; Garibaldi, Elisabetta; Tessa, Maria; Moro, Gregorio; Girelli, Giuseppe; Gabriele, Pietro

2016-02-24

The aim of this work is to develop an algorithm to predict recurrence in prostate cancer patients treated with radical radiotherapy, getting up to a prognostic power higher than traditional D'Amico risk classification. Two thousand four hundred ninety-three men belonging to the EUREKA-2 retrospective multi-centric database on prostate cancer and treated with external-beam radiotherapy as primary treatment comprised the study population. A Cox regression time to PSA failure analysis was performed in univariate and multivariate settings, evaluating the predictive ability of age, pre-treatment PSA, clinical-radiological staging, Gleason score and percentage of positive cores at biopsy (%PC). The accuracy of this model was checked with bootstrapping statistics. Subgroups for all the variables' combinations were combined to classify patients into five different "Candiolo" risk-classes for biochemical Progression Free Survival (bPFS); thereafter, they were also applied to clinical PFS (cPFS), systemic PFS (sPFS) and Prostate Cancer Specific Survival (PCSS), and compared to D'Amico risk grouping performances. The Candiolo classifier splits patients in 5 risk-groups with the following 10-years bPFS, cPFS, sPFS and PCSS: for very-low-risk 90 %, 94 %, 100 % and 100 %; for low-risk 74 %, 88 %, 94 % and 98 %; for intermediate-risk 60 %, 82 %, 91 % and 92 %; for high-risk 43 %, 55 %, 80 % and 89 % and for very-high-risk 14 %, 38 %, 56 % and 70 %. Our classifier outperforms D'Amico risk classes for all the end-points evaluated, with concordance indexes of 71.5 %, 75.5 %, 80 % and 80.5 % versus 63 %, 65.5 %, 69.5 % and 69 %, respectively. Our classification tool, combining five clinical and easily available parameters, seems to better stratify patients in predicting prostate cancer recurrence after radiotherapy compared to the traditional D'Amico risk classes.

Patterns and Predictors of Early Biochemical Recurrence After Radical Prostatectomy and Adjuvant Radiation Therapy in Men With pT{sub 3}N{sub 0} Prostate Cancer: Implications for Multimodal Therapies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Briganti, Alberto, E-mail: briganti.alberto@hsr.it; Joniau, Steven; Gandaglia, Giorgio

Purpose: The aim of our study was to evaluate patterns and predictors of early biochemical recurrence (eBCR) after radical prostatectomy (RP) and adjuvant radiation therapy (aRT) in order to identify which individuals might benefit from additional treatments. Methods and Materials: We evaluated 390 patients with pT{sub 3}N{sub 0} prostate cancer (PCa) receiving RP and aRT at 6 European centers between 1993 and 2006. Patients who were free from BCR at <2 years' follow-up were excluded. This resulted in 374 assessable patients. Early BCR was defined as 2 consecutive prostate-specific antigen (PSA) test values >0.2 ng/mL within 2 or 3 yearsmore » after aRT. Uni- and multivariable Cox regression analyses predicting overall and eBCR after aRT were fitted. Covariates consisted of preoperative PSA results, surgical margins, pathological stage, Gleason score, and aRT dose. Results: Overall, 5- and 8-year BCR-free survival rates were 77.1% and 70.8%, respectively. At a median follow-up of 86 months after aRT, 33 (8.8%) and 55 (14.6%) men experienced BCR within 2 or 3 years after aRT, respectively. In multivariable analyses, Gleason scores of 8 to 10 represented the only independent predictor of eBCR after aRT (all, P≤.01). The risk of BCR was significantly higher in patients with a Gleason score of 8 to 10 disease than in those with Gleason 2 to 6 within 24 months after treatment, after adjusting for all covariates (all, P≤.04). However, given a 24-month BCR free period, the risk of subsequent BCR for men with poorly differentiated disease was equal to that of men with less aggressive disease (all, P≥.3). Conclusions: High Gleason score represents the only predictor of eBCR after RP and aRT in patients affected by pT{sub 3}N{sub 0} PCa. Given the association between early PSA recurrence, clinical progression, and mortality, these patients might be considered candidates for adjuvant medical therapy and/or prophylactic whole-pelvis radiation therapy in addition to aRT, delivered to the prostatic bed.« less

¹⁸F-choline positron emission tomography/computed tomography-driven high-dose salvage radiation therapy in patients with biochemical progression after radical prostatectomy: feasibility study in 60 patients.

PubMed

D'Angelillo, Rolando M; Sciuto, Rosa; Ramella, Sara; Papalia, Rocco; Jereczek-Fossa, Barbara A; Trodella, Luca E; Fiore, Michele; Gallucci, Michele; Maini, Carlo L; Trodella, Lucio

2014-10-01

To retrospectively review data of a cohort of patients with biochemical progression after radical prostatectomy, treated according to a uniform institutional treatment policy, to evaluate toxicity and feasibility of high-dose salvage radiation therapy (80 Gy). Data on 60 patients with biochemical progression after radical prostatectomy between January 2009 and September 2011 were reviewed. The median value of prostate-specific antigen before radiation therapy was 0.9 ng/mL. All patients at time of diagnosis of biochemical recurrence underwent dynamic (18)F-choline positron emission tomography/computed tomography (PET/CT), which revealed in all cases a local recurrence. High-dose salvage radiation therapy was delivered up to total dose of 80 Gy to 18F-choline PET/CT-positive area. Toxicity was recorded according to the Common Terminology Criteria for Adverse Events, version 3.0, scale. Treatment was generally well tolerated: 54 patients (90%) completed salvage radiation therapy without any interruption. Gastrointestinal grade ≥2 acute toxicity was recorded in 6 patients (10%), whereas no patient experienced a grade ≥2 genitourinary toxicity. No grade 4 acute toxicity events were recorded. Only 1 patient (1.7%) experienced a grade 2 gastrointestinal late toxicity. With a mean follow-up of 31.2 months, 46 of 60 patients (76.6%) were free of recurrence. The 3-year biochemical progression-free survival rate was 72.5%. At early follow-up, (18)F-choline PET/CT-driven high-dose salvage radiation therapy seems to be feasible and well tolerated, with a low rate of toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

{sup 18}F-Choline Positron Emission Tomography/Computed Tomography–Driven High-Dose Salvage Radiation Therapy in Patients With Biochemical Progression After Radical Prostatectomy: Feasibility Study in 60 Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

D'Angelillo, Rolando M., E-mail: r.dangelillo@unicampus.it; Sciuto, Rosa; Ramella, Sara

Purpose: To retrospectively review data of a cohort of patients with biochemical progression after radical prostatectomy, treated according to a uniform institutional treatment policy, to evaluate toxicity and feasibility of high-dose salvage radiation therapy (80 Gy). Methods and Materials: Data on 60 patients with biochemical progression after radical prostatectomy between January 2009 and September 2011 were reviewed. The median value of prostate-specific antigen before radiation therapy was 0.9 ng/mL. All patients at time of diagnosis of biochemical recurrence underwent dynamic {sup 18}F-choline positron emission tomography/computed tomography (PET/CT), which revealed in all cases a local recurrence. High-dose salvage radiation therapy was delivered up tomore » total dose of 80 Gy to 18F-choline PET/CT-positive area. Toxicity was recorded according to the Common Terminology Criteria for Adverse Events, version 3.0, scale. Results: Treatment was generally well tolerated: 54 patients (90%) completed salvage radiation therapy without any interruption. Gastrointestinal grade ≥2 acute toxicity was recorded in 6 patients (10%), whereas no patient experienced a grade ≥2 genitourinary toxicity. No grade 4 acute toxicity events were recorded. Only 1 patient (1.7%) experienced a grade 2 gastrointestinal late toxicity. With a mean follow-up of 31.2 months, 46 of 60 patients (76.6%) were free of recurrence. The 3-year biochemical progression-free survival rate was 72.5%. Conclusions: At early follow-up, {sup 18}F-choline PET/CT-driven high-dose salvage radiation therapy seems to be feasible and well tolerated, with a low rate of toxicity.« less

Incidental prostate cancer at the time of cystectomy: the incidence and clinicopathological features in Chinese patients.

PubMed

Pan, Jiahua; Xue, Wei; Sha, Jianjun; Yang, Hu; Xu, Fan; Xuan, Hanqing; Li, Dong; Huang, Yiran

2014-01-01

To evaluate the incidence and the clinicopathological features of incidental prostate cancer detected in radical cystoprostatectomy (RCP) specimens in Chinese men and to estimate the oncological risk of prostate apex-sparing surgery for such patients. The clinical data and pathological feature of 504 patients who underwent RCP for bladder cancer from January 1999 to March 2013 were retrospectively reviewed. Whole mount serial section of the RCP specimens were cut transversely at 3-4 mm intervals and examined in same pathological institution. Thirty-four out of 504 patients (6.8%) had incidental prostate cancer with a mean age of 70.3 years. 12 cases (35.2%) were diagnosed as significant disease. 4 cases were found to have apex involvement of adenocarcinoma of the prostate while in 5 cases the prostate stroma invasion by urothelial carcinoma were identified (one involved prostate apex). The mean follow-up time was 46.4±33.8 months. Biochemical recurrence occurred in 3 patients but no prostate cancer-related death during the follow-up. There was no statistical significance in cancer specific survival between the clinically significant and insignificant cancer group. The prevalence of incidental prostate cancer in RCP specimens in Chinese patients was remarkably lower than in western people. Most of the incidental prostate cancer was clinically insignificant and patient's prognosis was mainly related to the bladder cancer. Sparing the prostate apex was potentially associated with a 1.0% risk of leaving significant cancer of the prostate or urothelial carcinoma.

Obese frailty, physical performance deficits, and falls in older men with biochemical recurrence of prostate cancer on androgen deprivation therapy: a case-control study

PubMed Central

Bylow, Kathryn; Hemmerich, Joshua; Mohile, Supriya G.; Stadler, Walter M.; Sajid, Saleha; Dale, William

2010-01-01

Objectives Early androgen deprivation therapy (ADT) has no proven survival advantage in older men with biochemical recurrence (BCR) of prostate cancer (PCa), and it may contribute to geriatric frailty; we tested this hypothesis. Methods We conducted a case-control study of men aged 60+ with BCR on ADT (n=63) versus PCa survivors without recurrence (n=71). Frailty prevalence, “obese” frailty, Short Physical Performance Battery (SPPB) scores and falls were compared. An exploratory analysis of frailty biomarkers (CRP, ESR, hemoglobin, albumin, and total cholesterol) was performed. Summary statistics, univariate and multivariate regression analyses were conducted. Results More patients on ADT were obese (BMI >30; 46.2% vs. 20.6%; p=0.03). There were no statistical differences in SPPB (p=0.41) or frailty (p=0.20). Using a proposed “obese” frailty criteria, 8.7% in ADT group were frail and 56.5% were “prefrail”, compared with 2.9% and 48.8% of controls (p=0.02). Falls in the last year were higher in ADT group (14.3% vs. 2.8%; p=0.02). In analyses controlling for age, clinical characteristics, and comorbidities, the ADT group trended toward significance for “obese” frailty (p = 0.14) and falls (OR = 4.74, p = 0.11). Comorbidity significantly increased the likelihood of “obese” frailty (p=0.01) and falls (OR 2.02, p = 0.01). Conclusions Men with BCR on ADT are frailer using proposed modified “obese” frailty criteria. They may have lower performance status and more falls. A larger, prospective trial is necessary to establish a causal link between ADT use and progression of frailty and disability. PMID:21269665

Biochemical and Genetic Markers in Aggressiveness and Recurrence of Prostate Cancer: Race-Specific Links to Inflammation and Insulin Resistance

DTIC Science & Technology

2013-07-01

as a statistical graphic, and Pearson product moment correlation coefficients as measures of the strength of linear association; 4) performing SNP ...determine if there are differences in single nucleotide polymorphisms ( SNPs ) in selected candidate genes implicated in metabolic syndrome, obesity, chronic...samples for the serum and SNP analyses. We have reached a target of 500 patients at the end of year 2; however, some of the patients turned out to be

Role of NuSAP in Prostate Tumor Progression

DTIC Science & Technology

2012-06-01

12: R64. 14 Amemiya H, Menolascino F, Pena A. Role of the expression of c-Met receptor in the progression of gastric cancer. Invest Clin 2010; 51: 369... histopathologic effects and biochemical recurrence. Urology 2004; 63: 1184 - 1190. 25 Monge M, Colas E, Doll A, Gil-Moreno A, Castellvi J, Diaz B et al...protein 6, a proliferation marker superior to Ki-67 and independent predictor of survival in patients with mantle cell lymphoma . Br J Cancer 2005; 93

Evaluation of the Prostate Bed for Local Recurrence After Radical Prostatectomy Using Endorectal Magnetic Resonance Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.edu; Pitroda, Sean P.; Eggener, Scott E.

Purpose: To summarize the results of a 4-year period in which endorectal magnetic resonance imaging (MRI) was considered for all men referred for salvage radiation therapy (RT) at a single academic center; to describe the incidence and location of locally recurrent disease in a contemporary cohort of men with biochemical failure after radical prostatectomy (RP), and to identify prognostic variables associated with MRI findings in order to define which patients may have the highest yield of the study. Methods and Materials: Between 2007 and 2011, 88 men without clinically palpable disease underwent eMRI for detectable prostate-specific antigen (PSA) after RP.more » The median interval between RP and eMRI was 32 months (interquartile range, 14-57 months), and the median PSA level was 0.30 ng/mL (interquartile range, 0.19-0.72 ng/mL). Magnetic resonance imaging scans consisting of T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging were evaluated for features consistent with local recurrence. The prostate bed was scored from 0-4, whereby 0 was definitely normal, 1 probably normal, 2 indeterminate, 3 probably abnormal, and 4 definitely abnormal. Local recurrence was defined as having a score of 3-4. Results: Local recurrence was identified in 21 men (24%). Abnormalities were best appreciated on T2-weighted axial images (90%) as focal hypointense lesions. Recurrence locations were perianastomotic (67%) or retrovesical (33%). The only risk factor associated with local recurrence was PSA; recurrence was seen in 37% of men with PSA >0.3 ng/mL vs 13% if PSA {<=}0.3 ng/mL (P<.01). The median volume of recurrence was 0.26 cm{sup 3} and was directly associated with PSA (r=0.5, P=.02). The correlation between MRI-based tumor volume and PSA was even stronger in men with positive margins (r=0.8, P<.01). Conclusions: Endorectal MRI can define areas of local recurrence after RP in a minority of men without clinical evidence of disease, with yield related to PSA. Further study is necessary to determine whether eMRI can improve patient selection and success of salvage RT.« less

Prospective Evaluation of 68Ga-RM2 PET/MRI in Patients with Biochemical Recurrence of Prostate Cancer and Negative Findings on Conventional Imaging.

PubMed

Minamimoto, Ryogo; Sonni, Ida; Hancock, Steven; Vasanawala, Shreyas; Loening, Andreas; Gambhir, Sanjiv S; Iagaru, Andrei

2018-05-01

68 Ga-labeled DOTA-4-amino-1-carboxymethyl-piperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH 2 ( 68 Ga-RM2) is a synthetic bombesin receptor antagonist that targets gastrin-releasing peptide receptor (GRPr). GRPr proteins are highly overexpressed in several human tumors, including prostate cancer (PCa). We present data from the use of 68 Ga-RM2 in patients with biochemical recurrence (BCR) of PCa and negative findings on conventional imaging. Methods: We enrolled 32 men with BCR of PCa, who were 59-83 y old (mean ± SD, 68.7 ± 6.4 y). Imaging started at 40-69 min (mean, 50.5 ± 6.8 min) after injection of 133.2-151.7 MBq (mean, 140.6 ± 7.4 MBq) of 68 Ga-RM2 using a time-of-flight-enabled simultaneous PET/MRI scanner. T1-weighted, T2-weighted, and diffusion-weighted images were acquired. Results: All patients had a rising level of prostate-specific antigen (PSA) (range, 0.3-119.0 ng/mL; mean, 10.1 ± 21.3 ng/mL) and negative findings on conventional imaging (CT or MRI, and a 99m Tc-methylene diphosphonate bone scan) before enrollment. The observed 68 Ga-RM2 PET detection rate was 71.8%. 68 Ga-RM2 PET identified recurrent PCa in 23 of the 32 participants, whereas the simultaneous MRI scan identified findings compatible with recurrent PCa in 11 of the 32 patients. PSA velocity was 0.32 ± 0.59 ng/mL/y (range, 0.04-1.9 ng/mL/y) in patients with negative PET findings and 2.51 ± 2.16 ng/mL/y (range, 0.13-8.68 ng/mL/y) in patients with positive PET findings ( P = 0.006). Conclusion: 68 Ga-RM2 PET can be used for assessment of GRPr expression in patients with BCR of PCa. High uptake in multiple areas compatible with cancer lesions suggests that 68 Ga-RM2 is a promising PET radiopharmaceutical for localization of disease in patients with BCR of PCa and negative findings on conventional imaging. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Prediction of outcome following early salvage radiotherapy among patients with biochemical recurrence after radical prostatectomy.

PubMed

Briganti, Alberto; Karnes, R Jeffrey; Joniau, Steven; Boorjian, Stephen A; Cozzarini, Cesare; Gandaglia, Giorgio; Hinkelbein, Wolfgang; Haustermans, Karin; Tombal, Bertrand; Shariat, Shahrokh; Sun, Maxine; Karakiewicz, Pierre I; Montorsi, Francesco; Van Poppel, Hein; Wiegel, Thomas

2014-09-01

Early salvage radiotherapy (eSRT) represents the only curative option for prostate cancer patients experiencing biochemical recurrence (BCR) for local recurrence after radical prostatectomy (RP). To develop and internally validate a novel nomogram predicting BCR after eSRT in patients treated with RP. Using a multi-institutional cohort, 472 node-negative patients who experienced BCR after RP were identified. All patients received eSRT, defined as local radiation to the prostate and seminal vesicle bed, delivered at prostate-specific antigen (PSA) ≤ 0.5 ng/ml. BCR after eSRT was defined as two consecutive PSA values ≥ 0.2 ng/ml. Uni- and multivariable Cox regression models predicting BCR after eSRT were fitted. Regression-based coefficients were used to develop a nomogram predicting the risk of 5-yr BCR after eSRT. The discrimination of the nomogram was quantified with the Harrell concordance index and the calibration plot method. Two hundred bootstrap resamples were used for internal validation. Mean follow-up was 58 mo (median: 48 mo). Overall, 5-yr BCR-free survival rate after eSRT was 73.4%. In univariable analyses, pathologic stage, Gleason score, and positive surgical margins were associated with the risk of BCR after eSRT (all p ≤ 0.04). These results were confirmed in multivariable analysis, where all the previously mentioned covariates as well as pre-RT PSA were significantly associated with BCR after eSRT (all p ≤ 0.04). A coefficient-based nomogram demonstrated a bootstrap-corrected discrimination of 0.74. Our study is limited by its retrospective nature and use of BCR as an end point. eSRT leads to excellent cancer control in patients with BCR for presumed local failure after RP. We developed the first nomogram to predict outcome after eSRT. Our model facilitates risk stratification and patient counselling regarding the use of secondary therapy for individuals experiencing BCR after RP. Salvage radiotherapy leads to optimal cancer control in patients who experience recurrence after radical prostatectomy. We developed a novel tool to identify the best candidates for salvage treatment and to allow selection of patients to be considered for additional forms of therapy. Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Contrast enhanced ultrasound (CEUS) with MRI image fusion for monitoring focal therapy of prostate cancer with high intensity focused ultrasound (HIFU)1.

PubMed

Apfelbeck, M; Clevert, D-A; Ricke, J; Stief, C; Schlenker, B

2018-01-01

Reduced acceptance of radical prostatectomy in patients with low risk or intermediate risk prostate cancer has significantly changed treatment strategies in prostate cancer (PCa) during the last years. Focal therapy of the prostate with high intensity focused ultrasound (HIFU) is an organ-preserving treatment for prostate cancer with less impairment of health-related quality of life. Follow-up after HIFU therapy by imaging modalities remains a major problem as eg. MRI performs poorly. Contrast enhanced ultrasound (CEUS) allows to monitor the vascular architecture of organs non-invasively. However, only limited data are available using CEUS to define successful and complete HIFU treatment of the prostate. In this study, we aimed to evaluate short-term image findings using CEUS and image fusion before and after HIFU treatment. Prospective single arm study in patients with uni- or bilateral, low or intermediate risk prostate cancer or recurrent cancer after radiotherapy treated with HIFU at our institution between October 2016 and November 2017. HIFU hemiablation or whole gland treatment was performed using the Focal One® device. PCa was diagnosed either by multiparametric magnetic resonance imaging (mpMRI) followed by MRI fusion based targeted biopsy combined with 12 core transrectal ultrasound (TRUS) guided biopsy or 12 core random biopsy only. Monitoring of the target region before, immediately and 24 hours after the ablation was done by CEUS in combination with image fusion using an axial T2-weighted MRI sequence. 6 consecutive patients with Gleason score (GS) 6, 5 patients with GS 7a prostate cancer and one patient with biochemical recurrence after radiotherapy were included in the study. Three patients underwent whole gland treatment due to histological proven bilateral PCa or recurrent PCa after radiotherapy. Hemiablation was performed in 9 patients with unilateral tumor and no PIRADS 4 or 5 lesion in the contralateral lobe. Median patient age was 69.8 years and median PSA (prostate-specific antigen) level was 8.4 ng/ml. CEUS showed markedly reduced microbubbles in the ablated area, the prostate capsule still showed signs of perfusion. The study is limited by the short follow up and small number of patients. CEUS examination showed a reduction of microcirculation in the treated area immediately after the treatment and 24 hours later. The combination of CEUS and image fusion seems to be helpful for detecting the PCa target lesion and monitor the success of HIFU ablation treatment. Evidence for image findings after HIFU-therapy are rare. Further studies on this topic are needed.

[Expression of SRD5A1 and its prognostic role in prostate cancer: Analysis based on the data-mining of ONCOMINE].

PubMed

Xu, Bin; Liu, Ning; Chen, Shu-Qiu; Jiang, Hua; Zhang, Li-Jie; Zhang, Xiao-Wen; Yang, Yu; Sha, Guo-Zhu; Liu, Jing; Zhu, Wei-Dong; Chen, Ming

2016-09-01

To explore the expression of I-5α-reductase (SRD5A1)and its prognostic role in prostate cancer . Data about SRD5A1 were retrieved from the ONCOMINE database and the role of SRD5A1 in prostate cancer was analyzed. Totally, 992 studies of different types relevant to the expression of SRD5A1 were identified in the ONCOMINE database. The SRD5A1 expression was statistically significant in 239 of the studies, overexpressed in 157 (11 in prostate cancer) and underexpressed in the other 82 (3 in prostate cancer). Eighteen of the studies, with 1 068 samples, addressed the expression of SRD5A1 in prostate cancer and normal tissues, which was significantly higher in the former than in the latter tissue (P<0.05). In 3 of the studies, the SRD5A1 expression was high in primary prostate cancer and increased with its metastasis (P<0.0 5). Two of the studies with prognostic data showed a higher rate of postoperative biochemical recurrence and a higher total mortality rate in the patients with a high than in those with a low expression of SRD5A1 (P<0.05). SRD5A1 is highly expressed in prostate cancer, especially in metastatic and castration-resistant prostate cancer and its expression is associated with the prognosis of prostate cancer, which may be an important target of medication for prostate cancer.

GTI-2040 and Docetaxel in Treating Patients With Recurrent, Metastatic, or Unresectable Locally Advanced Non-Small Cell Lung Cancer, Prostate Cancer, or Other Solid Tumors

ClinicalTrials.gov

2013-01-23

Recurrent Non-small Cell Lung Cancer; Recurrent Prostate Cancer; Stage III Prostate Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Prostate Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Coffee and tea consumption in relation to prostate cancer prognosis

PubMed Central

Geybels, Milan S.; Neuhouser, Marian L.; Wright, Jonathan L.; Stott-Miller, Marni; Stanford, Janet L.

2013-01-01

Background Bioactive compounds found in coffee and tea may delay the progression of prostate cancer. Methods We investigated associations of pre-diagnostic coffee and tea consumption with risk of prostate cancer recurrence/progression. Study participants were men diagnosed with prostate cancer in 2002–2005 in King County, Washington, USA. We assessed the usual pattern of coffee and tea consumption two years before diagnosis date. Prostate cancer outcome events were identified using a detailed follow-up survey. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results The analysis of coffee intake in relation to prostate cancer recurrence/progression included 630 patients with a median follow-up of 6.4 years, during which 140 prostate cancer recurrence/progression events were recorded. Approximately 61% of patients consumed at least one cup of coffee per day. Coffee consumption was associated with a reduced risk of prostate cancer recurrence/progression; the adjusted HR for ≥4 cups/day versus ≤1 cup/week was 0.41 (95% CI: 0.20, 0.81; P for trend = 0.01). Approximately 14% of patients consumed one or more cups of tea per day, and tea consumption was unrelated to prostate cancer recurrence/progression. Conclusion Results indicate that pre-diagnostic coffee consumption is associated with a lower risk of prostate cancer recurrence/progression. This finding will require replication in larger studies. PMID:23907772

Comparison of 68Ga-labelled PSMA-11 and 11C-choline in the detection of prostate cancer metastases by PET/CT.

PubMed

Schwenck, Johannes; Rempp, Hansjoerg; Reischl, Gerald; Kruck, Stephan; Stenzl, Arnulf; Nikolaou, Konstantin; Pfannenberg, Christina; la Fougère, Christian

2017-01-01

Prostate-specific membrane antigen (PSMA) is expressed ubiquitously on the membrane of most prostate tumors and its metastasis. While PET/CT using 11 C-choline was considered as the gold standard in the staging of prostate cancer, PET with radiolabelled PSMA ligands was introduced into the clinic in recent years. Our aim was to compare the PSMA ligand 68 Ga-PSMA-11 with 11 C-choline in patients with primary and recurrent prostate cancer. 123 patients underwent a whole-body PET/CT examination using 68 Ga-PSMA-11 and 11 C-choline. Suspicious lesions were evaluated visually and semiquantitatively (SUVavg). Out of these, 103 suffered from a confirmed biochemical relapse after prostatectomy and/or radiotherapy (mean PSA level of 4.5 ng/ml), while 20 patients underwent primary staging. In 67 patients with biochemical relapse, we detected 458 lymph nodes suspicious for metastasis. PET using 68 Ga-PSMA-11 showed a significantly higher uptake and detection rate than 11 C-choline PET. Also 68 Ga-PSMA-11 PET identified significantly more patients with suspicious lymph nodes as well as affected lymph nodes regions especially at low PSA levels. Bone lesions suspicious for prostate cancer metastasis were revealed in 36 patients' biochemical relapse. Significantly more bone lesions were detected by 68 Ga-PSMA-11, but only 3 patients had only PSMA-positive bone lesions. Nevertheless, we detected also 29 suspicious lymph nodes and 8 bone lesions, which were only positive as per 11 C-choline PET. These findings led to crucial differences in the TNM classification and the identification of oligometastatic patients. In the patients who underwent initial staging, all primary tumors showed uptake of both tracers. Although significantly more suspicious lymph nodes and bone lesions were identified, only 2 patients presented with bone lesions only detected by 68 Ga-PSMA-11 PET. Thus, PET using 68 Ga-PSMA-11 showed a higher detection rate than 11 C-choline PET for lymph nodes as well as bone lesions. However, we found lymph nodes and bone lesions which were not concordant applying both tracers.

A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Biochemically Monoclonal Antibody J591 in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer

DTIC Science & Technology

2010-09-01

relapsed prostate cancer (PC) after local therapy. J Clin Oncol 28: 15s, 2010 (suppl; Abstr TPS248) Presentation: Poster presentation, 2010 ASCO...Annual Meeting V. Conclusions Biochemical relapse is common after local therapy for prostate cancer. Based on the physical properties of 177Lu...ketoconazole in patients (pts) with high-risk castrate biochemically relapsed prostate cancer (PC) after local therapy. S. T. Tagawa, J. Osborne, P. J

Decreased expression of serine protease inhibitor family G1 (SERPING1) in prostate cancer can help distinguish high-risk prostate cancer and predicts malignant progression.

PubMed

Peng, Shengmeng; Du, Tao; Wu, Wanhua; Chen, Xianju; Lai, Yiming; Zhu, Dingjun; Wang, Qiong; Ma, Xiaoming; Lin, Chunhao; Li, Zean; Guo, Zhenghui; Huang, Hai

2018-06-11

The aim of this study was to investigate the associations of serine proteinase inhibitor family G1 (SERPING1) down-regulation with poor prognosis in patients with prostate cancer (PCa). Furthermore, we aim to find more novel and effective PCa molecular markers to provide an early screening of PCa, distinguish patients with aggressive PCa, predict the prognosis, or reduce the economic burden of PCa. SERPING1 protein expression in both human PCa and normal prostate tissues was detected by immunohistochemical staining, which intensity was analyzed in association with clinical pathological parameters such Gleason score, pathological grade, clinical stage, tumor stage, lymph node metastasis, and distant metastasis. Moreover, we used The Cancer Genome Atlas (TCGA) Database, Taylor Database, and Oncomine dataset to validate our immunohistochemical results and investigated the value of SERPING1 in PCa at mRNA level. Kaplan-Meier analysis and Cox regression analysis were performed to evaluate the relationship between SERPING1 and prognosis of patients with PCa. The outcome showed that SERPING1 was expressed mainly in cytoplasm of grand cells of prostate tissue and was significantly expressed less in PCa (P<0.001). Furthermore, in the tissue microarray of our samples, decreasing expression of SERPING1 was correlated with the higher Gleason score (P = 0.004), the higher pathological grade (P = 0.01) and the advanced tumor stage (P = 0.005) at protein level. In TCGA dataset and Taylor Dataset, low-expressed SERPING1 was correlated with the younger patient (P = 0.02 in TCGA, P = 0.044 in Taylor) and the higher Gleason score (P = 0.019 in TCGA, P<0.001 in Taylor) at mRNA level. Kaplan-Meier analysis revealed that the lower mRNA of SERPING1 predicted lower overall survivals (P = 0.027 in TCGA), lower disease-free survival (P = 0.029) and lower biochemical recurrence-free survival (P = 0.011 in Taylor). Data from Oncomine database shown that SERPING1 low expression implying higher malignancy of prostate lesions. Using multivariate analysis, we also found that SERPING1 expression was independent prognostic marker of poor disease-free survival and biochemical recurrence-free survival. SERPING1 may play an important role in PCa and can be serve as a novel marker in diagnosis and prognostic prediction in PCa. In addition, levels of SERPING1 can help identify low-risk prostate to provide reference for patients with PCa to accept active surveillance and reduce overtreatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Comparison of the Walz Nomogram and Presence of Secondary Circulating Prostate Cells for Predicting Early Biochemical Failure after Radical Prostatectomy for Prostate Cancer in Chilean Men.

PubMed

Murray, Nigel P; Reyes, Eduardo; Orellana, Nelson; Fuentealba, Cynthia; Jacob, Omar

2015-01-01

To determine the utility of secondary circulating prostate cells for predicting early biochemical failure after radical prostatectomy for prostate cancer and compare the results with the Walz nomagram. A single centre, prospective study of men with prostate cancer treated with radical prostatectomy between 2004 and 2014 was conducted, with registration of clinical-pathological details, total serum PSA pre-surgery, Gleason score, extracapsular extension, positive surgical margins, infiltration of lymph nodes, seminal vesicles and pathological stage. Secondary circulating prostate cells were obtained using differential gel centrifugation and assessed using standard immunocytochemistry with anti-PSA. Biochemical failure was defined as a PSA >0.2ng/ml, predictive values werecalculated using the Walz nomagram and CPC detection. A total of 326 men participated, with a median follow up of 5 years; 64 had biochemical failure within two years. Extracapsular extension, positive surgical margins, pathological stage, Gleason score ≥ 8, infiltration of seminal vesicles and lymph nodes were all associated with higher risk of biochemical failure. The discriminative value for the nomogram and circulating prostate cells was high (AUC >0.80), predictive values were higher for circulating prostate cell detection, with a negative predictive value of 99%, sensitivity of 96% and specificity of 75%. The nomagram had good predictive power to identify men with a high risk of biochemical failure within two years. The presence of circulating prostate cells had the same predictive power, with a higher sensitivity and negative predictive value. The presence of secondary circulating prostate cells identifies a group of men with a high risk of early biochemical failure. Those negative for secondary CPCs have a very low risk of early biochemical failure.

Reduction in PSA messenger-RNA expression and clinical recurrence in patients with prostatic cancer undergoing neoadjuvant therapy before radical prostatectomy

PubMed Central

Grasso, Marco; Lania, Caterina; Blanco, Salvatore; Baruffi, Marco; Mocellin, Simone

2004-01-01

Background We assessed the incidence of micro-metastases at surgical margins (SM) and pelvic lymph nodes (LN) in patients submitted to radical retropubic prostatectomy (RP) after neoadjuvant therapy (NT) or to RP alone. We compared traditional staging to molecular detection of PSA using Taqman-based quantitative real-time PCR (qrt-PCR) never used before for this purpose. Methods 29 patients were assigned to NT plus RP (arm A) or RP alone (arm B). Pelvic LN were dissected for qrt-PCR analysis, together with right and left lateral SM. Results 64,3% patients of arm B and 26.6% of arm A had evidence of PSA mRNA expression in LN and/or SM. 17,2% patients, all of arm B, had biochemical recurrence. Conclusions Qrt-PCR may be more sensitive, compared to conventional histology, in identifying presence of viable prostate carcinoma cells in SM and LN. Gene expression of PSA in surgical periprostatic samples might be considered as a novel and reliable indicator of minimal residual disease after NT. PMID:15104791

Long-term prognostic significance of rising PSA levels following radiotherapy for localized prostate cancer - focus on overall survival.

PubMed

Freiberger, Carla; Berneking, Vanessa; Vögeli, Thomas-Alexander; Kirschner-Hermanns, Ruth; Eble, Michael J; Pinkawa, Michael

2017-06-14

The aim of this study was to evaluate the long-term prognostic significance of rising PSA levels, particularly focussing on overall survival. Two hundred ninety-five patients with localized prostate cancer were either treated with low-dose-rate (LDR) brachytherapy with I-125 seeds as monotherapy (n = 94; 145Gy), high-dose-rate (HDR) brachytherapy with Ir-192 as a boost to external beam RT (n = 66; 50.4Gy in 1.8Gy fractions EBRT + 18Gy in 9Gy fractions HDR) or EBRT alone (70.2Gy in 1.8Gy fractions; n = 135). "PSA bounce" was defined as an increase of at least 0.2 ng/ml followed by spontaneous return to pre-bounce level or lower, biochemical failure was defined according to the Phoenix definition. Median follow-up after the end of radiotherapy was 108 months. A PSA bounce showed to be a significant factor for biochemical control (BC) and overall survival (OS) after ten years (BC10 of 83% with bounce vs. 34% without, p < 0.01; OS10 of 82% with bounce vs. 59% without bounce, p < 0.01). The occurrence of a bounce, a high nadir and the therapy modality (LDR-BT vs. EBRT and HDR-BT + EBRT vs. EBRT) proved to be independent factors for PSA recurrence in multivariate Cox regression analysis. A bounce was detected significantly earlier than a PSA recurrence (median 20 months vs. 32 months after RT; p < 0.01; median PSA doubling time 5.5 vs. 5.0 months, not significant). PSA doubling time was prognostically significant in case of PSA recurrence (OS10 of 72% vs. 36% with PSA doubling time ˃ 5 months vs. ≤ 5 months; p < 0.01). Rising PSA levels within the first two years can usually be classified as a benign PSA bounce, with favourable recurrence-free and overall survival rates. PSA doubling time is an important predictor for overall survival following the diagnosis of a recurrence.

[Significance and Value of PSMA Ligands in Prostate Cancer].

PubMed

Gasch, Claudia; Körber, Stefan; Kremer, Christophe; Eiber, Matthias; Kratochwil, Clemens; Haberkorn, Uwe; Hohenfellner, Markus; Hadaschik, Boris; Giesel, Frederik L

2017-04-01

In recent years, PSMA-targeting PET tracers such as 68 Ga-PSMA-11 have shown promising results, thus contributing to a better management of prostate cancer patients. At the present time, 68 Ga-PSMA-11 is most frequently used for diagnostic evaluation in the setting of biochemical recurrence of prostate cancer. In this context, the 68 Ga-PSMA-11 PET/CT delivers superior detection rates compared to conventional imaging, especially for the detection of small, unsuspicious lesions or lesions in the presence of low PSA values. Furthermore, 68 Ga-PSMA PET imaging seems to be an encouraging alternative for the staging of high-risk patients, particularly in combination with multiparametric MRI. In addition to the increasing use of PSMA ligands in clinical diagnostics, some variants have also been successfully applied in therapy. Advanced metastasized prostate cancer patients showed a good response to PSMA radioligand therapy with tolerable side-effects after failure of guideline-compliant treatment.Due to recent developments, PSMA ligands will continue to play an important role in the management of prostate cancer patients and will be more widely used in the future. © Georg Thieme Verlag KG Stuttgart · New York.

Does robotic prostatectomy meet its promise in the management of prostate cancer?

PubMed

Huang, Kuo-How; Carter, Stacey C; Hu, Jim C

2013-06-01

Following Walsh's advances in pelvic anatomy and surgical technique to minimize intraoperative peri-prostatic trauma more than 30 years ago, open retropubic radical prostatectomy (RRP) evolved to become the gold standard treatment of localized prostate cancer, with excellent long-term survival outcomes [1•]. However, RRP is performed with great heterogeneity, even among high volume surgeons, and subtle differences in surgical technique result in clinically significant differences in recovery of urinary and sexual function. Since the initial description of robotic-assisted radical prostatectomy (RARP) in 2000 [2], and U.S. Food and Drug Administration approval shortly thereafter, RARP has been rapidly adopted and has overtaken RRP as the most popular surgical approach in the management of prostate cancer in the United States [3]. However, the surgical management of prostate cancer remains controversial. This is confounded by the idolatry of new technologies and aggressive marketing versus conservatism in embracing tradition. Herein, we review the literature to compare RRP to RARP in terms of perioperative, oncologic, and quality-of-life outcomes as well as healthcare costs. This is a particularly relevant, given the absence of randomized trials and long-term (more than 10-year) follow-up for RARP biochemical recurrence-free survival.

Clinical significance of CXCL16/CXCR6 expression in patients with prostate cancer.

PubMed

Ha, Hong Koo; Lee, Wan; Park, Hyun Jun; Lee, Sang Don; Lee, Jeong Zoo; Chung, Moon Kee

2011-01-01

We hypothesized that the CXCL16-CXCR6 ligand-receptor system may play an important role in prostate cancer progression. Levels of CXCL16 and CXCR6 expression were evaluated in prostate cancer cell lines (PC-3 and LNCaP) and normal prostate epithelial cells (PrEC), as well as in tissues from 354 patients. The immunohistochemical expression of CXCL16/CXCR6 was greater in the PC-3/LNCaP cells than in the PrEC cell line. The expression of CXCL16/CXCR6 was significantly higher in prostate cancer than in benign prostatic hypertrophy. Using RT-PCR, the expression of CXCL16/CXCR6 was found to be greater in the PC-3/LNCaP cells than in the PrEC cell line. CXCL16/CXCR6 was weakly detected in lung and liver tissues, whereas CXCL16 was highly expressed in specimens of bone metastasis. CXCL16 immunostaining was related to Gleason score, T stage, tumor volume, perineural invasion and lymph node metastasis. However, biochemical PSA recurrence was not related to the expression of CXCL16/CXCR6. High CXCL16/CXCR6 expression may be related to aggressive cancer behavior, and high CXCL16 expression to bone metastases.

Associations between ABO blood groups and biochemical recurrence after radical prostatectomy.

PubMed

Ohno, Yoshio; Ohori, Makoto; Nakashima, Jun; Okubo, Hidenori; Satake, Naoya; Takizawa, Issei; Hashimoto, Takeshi; Hamada, Riu; Nakagami, Yoshihiro; Yoshioka, Kunihiko; Tachibana, Masaaki

2015-01-01

Recent studies have demonstrated associations between ABO blood groups and prognosis in various types of cancers. The aim of this study was to investigate the association between ABO blood groups and biochemical recurrence (BCR) after radical prostatectomy (RP). A total of 555 patients with prostate cancer who underwent RP were included in the study. No patients received neoadjuvant and/or adjuvant therapy. The effect of ABO blood groups on BCR was examined using univariate and multivariate analyses. During the follow-up period (mean, 52.0 months), 166 patients (29.9%) experienced BCR, with a 5-year BCR-free rate of 67.3%. Although the ABO blood group was not a significantly associated with BCR in the univariate analysis, it was an independent predictor of BCR in the multivariate analysis: blood type O patients had a significantly lower risk of BCR compared to type A patients (Hazard ratio, 0.608; 95% confidence interval, 0.410-0.902; P = 0.014). Further analyses revealed that surgical margin status confounded the assessment of the association between the ABO blood group and BCR. In the analyses of patients with a negative surgical margin, the 5-year BCR-free rate in blood type O patients was a significantly higher than that in type A patients (91.2% vs. 71.0%; P = 0.026). Blood type O is significantly associated with a decreased risk of biochemical recurrence after radical prostatectomy. Further studies are needed to clarify the nature of this association.

Expression of the TPα and TPβ isoforms of the thromboxane prostanoid receptor (TP) in prostate cancer: clinical significance and diagnostic potential.

PubMed

Mulvaney, Eamon P; Shilling, Christine; Eivers, Sarah B; Perry, Antoinette S; Bjartell, Anders; Kay, Elaine W; Watson, R William; Kinsella, B Therese

2016-11-08

The prostanoid thromboxane (TX)A2 plays a central role in haemostasis and is increasingly implicated in cancer progression. TXA2 signals through two T Prostanoid receptor (TP) isoforms termed TPα and TPβ, with both encoded by the TBXA2R gene. Despite exhibiting several functional and regulatory differences, the role of the individual TP isoforms in neoplastic diseases is largely unknown.This study evaluated expression of the TPα and TPβ isoforms in tumour microarrays of the benign prostate and different pathological (Gleason) grades of prostate cancer (PCa). Expression of TPβ was significantly increased in PCa relative to benign tissue and strongly correlated with increasing Gleason grade. Furthermore, higher TPβ expression was associated with increased risk of biochemical recurrence (BCR) and significantly shorter disease-free survival time in patients post-surgery. While TPα was more variably expressed than TPβ in PCa, increased/high TPα expression within the tumour also trended toward increased BCR and shorter disease-free survival time. Comparative genomic CpG DNA methylation analysis revealed substantial differences in the extent of methylation of the promoter regions of the TBXA2R that specifically regulate expression of TPα and TPβ, respectively, both in benign prostate and in clinically-derived tissue representative of precursor lesions and progressive stages of PCa. Collectively, TPα and TPβ expression is differentially regulated both in the benign and tumourigenic prostate, and coincides with clinical pathology and altered CpG methylation of the TBXA2R gene. Analysis of TPβ, or a combination of TPα/TPβ, expression levels may have significant clinical potential as a diagnostic biomarker and predictor of PCa disease recurrence.

Phase I/II trial of dendritic cell-based active cellular immunotherapy with DCVAC/PCa in patients with rising PSA after primary prostatectomy or salvage radiotherapy for the treatment of prostate cancer.

PubMed

Fucikova, Jitka; Podrazil, Michal; Jarolim, Ladislav; Bilkova, Pavla; Hensler, Michal; Becht, Etienne; Gasova, Zdenka; Klouckova, Jana; Kayserova, Jana; Horvath, Rudolf; Fialova, Anna; Vavrova, Katerina; Sochorova, Klara; Rozkova, Daniela; Spisek, Radek; Bartunkova, Jirina

2018-01-01

Immunotherapy of cancer has the potential to be effective mostly in patients with a low tumour burden. Rising PSA (prostate-specific antigen) levels in patients with prostate cancer represents such a situation. We performed the present clinical study with dendritic cell (DC)-based immunotherapy in this patient population. The single-arm phase I/II trial registered as EudraCT 2009-017259-91 involved 27 patients with rising PSA levels. The study medication consisted of autologous DCs pulsed with the killed LNCaP cell line (DCVAC/PCa). Twelve patients with a favourable PSA response continued with the second cycle of immunotherapy. The primary and secondary objectives of the study were to assess the safety and determine the PSA doubling time (PSADT), respectively. No significant side effects were recorded. The median PSADT in all treated patients increased from 5.67 months prior to immunotherapy to 18.85 months after 12 doses (p < 0.0018). Twelve patients who continued immunotherapy with the second cycle had a median PSADT of 58 months that remained stable after the second cycle. In the peripheral blood, specific PSA-reacting T lymphocytes were increased significantly already after the fourth dose, and a stable frequency was detected throughout the remainder of DCVAC/PCa treatment. Long-term immunotherapy of prostate cancer patients experiencing early signs of PSA recurrence using DCVAC/PCa was safe, induced an immune response and led to the significant prolongation of PSADT. Long-term follow-up may show whether the changes in PSADT might improve the clinical outcome in patients with biochemical recurrence of the prostate cancer.

Phase I Trial of Adenovirus-Mediated IL-12 Gene Transduction in Patients with Recurrent Locally Advanced Prostate Cancer Following Therapy

DTIC Science & Technology

2005-10-01

salvage seed implant, cryotherapy ) or who have a rising PSA while on hormone therapy for locally advanced prostate cancer are as follows: a. A...Gene Transduction in Patients with Recurrent Locally Advanced Prostate Cancer Following Therapy PRINCIPAL INVESTIGATOR: Simon J. Hall, MD...CONTRACT NUMBER Phase I Trial of Adenovirus-Mediated IL-12 Gene Transduction in Patients with Recurrent Locally Advanced Prostate Cancer Following

Akt Inhibitor MK2206 and Hydroxychloroquine in Treating Patients With Advanced Solid Tumors, Melanoma, Prostate or Kidney Cancer

ClinicalTrials.gov

2018-05-15

Adult Solid Neoplasm; Hormone-Resistant Prostate Carcinoma; Recurrent Melanoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Prostate Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7

Metformin effects on biochemical recurrence and metabolic signaling in the prostate.

PubMed

Winters, Brian; Plymate, Stephen; Zeliadt, Steven B; Holt, Sarah; Zhang, Xiaotun; Hu, Elaine; Lin, Daniel W; Morrissey, Colm; Wooldridge, Bryan; Gore, John L; Porter, Michael P; Wright, Jonathan L

2015-11-01

Metformin has received considerable attention as a potential anti-cancer agent. Animal and in-vitro prostate cancer (PCa) models have demonstrated decreased tumor growth with metformin, however the precise mechanisms are unknown. We examine the effects of metformin on PCa biochemical recurrence (BCR) in a large clinical database followed by evaluating metabolic signaling changes in a cohort of men undergoing prostate needle biopsy (PNB). Men treated for localized PCa were identified in a comprehensive clinical database between 2001 and 2010. Cox regression was performed to determine association with BCR relative to metformin use. We next identified a separate case-control cohort of men undergoing prostate needle biopsy (PNB) stratified by metformin use. Differences in mean IHC scores were compared with linear regression for phosphorylated IR, IGF-IR, AKT, and AMPK. One thousand seven hundred and thirty four men were evaluated for BCR with mean follow up of 41 months (range 1-121 months). "Ever" metformin use was not associated with BCR (HR 1.12, 0.77-1.65), however men reporting both pre/post-treatment metformin use had a 45% reduction in BCR (HR = 0.55 (0.31-0.96)). For the tissue-based study, 48 metformin users and 42 controls underwent PNB. Significantly greater staining in phosphorylated nuclear (p-IR, p-AKT) and cytoplasmic (p-IR, p-IGF-1R) insulin signaling proteins were seen in patients with PCa detected compared to those with negative PNB (P-values all <0.006). When stratified by metformin use, IGF-1R remained significantly elevated (P = 0.01) in men with PCa detected whereas p-AMPK (P = 0.05) was elevated only in those without PCa. Metformin use is associated with reduced BCR after treatment of localized PCa when considering pre-diagnostic and cumulative dosing. In men with cancer detected on PNB, insulin signaling markers were significantly elevated compared to negative PNB patients. The finding of IGF-1R elevation in positive PNBs versus p-AMPK elevation in negative PNBs suggests altered metabolic pathway activation precipitated by metformin use. © 2015 Wiley Periodicals, Inc.

Comparison of mRNA, Protein, and Urinary Nucleic Acid Levels of S100A8 and S100A9 between Prostate Cancer and BPH.

PubMed

Yun, Seok Joong; Yan, Chunri; Jeong, Pildu; Kang, Ho Won; Kim, Ye-Hwan; Kim, Eun-Ah; Lee, Ok-Jun; Kim, Won Tae; Moon, Sung-Kwon; Kim, Isaac Yi; Choi, Yung-Hyun; Kim, Wun-Jae

2015-07-01

Infections and inflammation in the prostate play a critical role in carcinogenesis, and S100A8 and S100A9 are key mediators in acute and chronic inflammation. Therefore, we investigated the differences of S100A8/A9 expression between prostate cancer (CaP) and benign prostatic hyperplasia (BPH) tissues, and we evaluated the possibilities of urinary nucleic acids of S100A8/A9 as diagnostic and prognostic markers. Tissues from 132 CaP patients who underwent prostatectomy or transurethral resection and 90 BPH patients who underwent transurethral prostatectomy were assessed.sd In addition, S100A8 and S100A9 nucleic acid levels were measured in the urine of 283 CaP patients and 363 BPH controls. S100A8 and S100A9 mRNA levels were lower in CaP than BPH tissues (P < 0.001). S100A8 and S100A9 expression was increased in cancer tissues with poorer prognosis. In 69 specimens from prostatectomy patients, S100A8/A9 were the independent predictor of biochemical recurrence (hazard ratio 5.22, 95 % confidence interval 1.800-15.155, P = 0.002). Immunohistochemical staining revealed that BPH tissues stained more strongly for both S100A8 and S100A9 than CaP tissues (P < 0.001). S100A8 and S100A9 urinary nucleic acid levels were lower in CaP than in BPH (P = 0.001 and <0.001, respectively). S100A8/A9 levels are lower in CaP than in BPH. Both were more highly expressed in patients with aggressive disease and shorter biochemical recurrence-free time. S100A8/A9 urinary cell-free nucleic acid levels correlated positively with expression levels obtained from tissue staining. Therefore, S100A8/A9 measurement in tissues and urine may have diagnostic and prognostic value in CaP.

Metformin Effects on Biochemical Recurrence and Metabolic Signaling in the Prostate

PubMed Central

Winters, Brian; Plymate, Stephen; Zeliadt, Steven B; Holt, Sarah; Zhang, Xiaotun; Hu, Elaine; Lin, Daniel W.; Morrissey, Colm; Wooldridge, Bryan; Gore, John L; Porter, Michael P; Wright, Jonathan L

2015-01-01

Background Metformin has received considerable attention as a potential anti-cancer agent. Animal and in-vitro prostate cancer (PCa) models have demonstrated decreased tumor growth with metformin, however the precise mechanisms are unknown. We examine the effects of metformin on PCa biochemical recurrence (BCR) in a large clinical database followed by evaluating metabolic signaling changes in a cohort of men undergoing prostate needle biopsy (PNB). Methods Men treated for localized PCa were identified in a comprehensive clinical database between 2001 and 2010. Cox regression was performed to determine association with BCR relative to metformin use. We next identified a separate case-control cohort of men undergoing prostate needle biopsy (PNB) stratified by metformin use. Differences in mean IHC scores were compared with linear regression for phosphorylated IR, IGF-IR, AKT, and AMPK. Results 1,734 men were evaluated for BCR with mean follow up of 41 months (range 1-121 months). ‘Ever’ metformin use was not associated with BCR (HR 1.12, 0.77-1.65), however men reporting both pre/post-treatment metformin use had a 45% reduction in BCR (HR=0.55 (0.31-0.96)). For the tissue-based study, 48 metformin users and 42 controls underwent PNB. Significantly greater staining in phosphorylated nuclear (p-IR, p-AKT) and cytoplasmic (p-IR, p-IGF-1R) insulin signaling proteins were seen in patients with PCa detected compared to those with negative PNB (p-values all < 0.006). When stratified by metformin use, IGF-1R remained significantly elevated (p=0.01) in men with PCa detected whereas p-AMPK (p=0.05) was elevated only in those without PCa. Conclusion Metformin use is associated with reduced BCR after treatment of localized PCa when considering pre-diagnostic and cumulative dosing. In men with cancer detected on PNB, insulin signaling markers were significantly elevated compared to negative PNB patients. The finding of IGF-1R elevation in positive PNBs versus p-AMPK elevation in negative PNBs suggests altered metabolic pathway activation precipitated by metformin use. PMID:26201966

Altered mitochondrial genome content signals worse pathology and prognosis in prostate cancer.

PubMed

Kalsbeek, Anton M F; Chan, Eva K F; Grogan, Judith; Petersen, Desiree C; Jaratlerdsiri, Weerachai; Gupta, Ruta; Lyons, Ruth J; Haynes, Anne-Maree; Horvath, Lisa G; Kench, James G; Stricker, Phillip D; Hayes, Vanessa M

2018-01-01

Mitochondrial genome (mtDNA) content is depleted in many cancers. In prostate cancer, there is intra-glandular as well as inter-patient mtDNA copy number variation. In this study, we determine if mtDNA content can be used as a predictor for prostate cancer staging and outcomes. Fresh prostate cancer biopsies from 115 patients were obtained at time of surgery. All cores underwent pathological review, followed by isolation of cancer and normal tissue. DNA was extracted and qPCR performed to quantify the total amount of mtDNA as a ratio to genomic DNA. Differences in mtDNA content were compared for prostate cancer pathology features and disease outcomes. We showed a significantly reduced mtDNA content in prostate cancer compared with normal adjacent prostate tissue (mean difference 1.73-fold, P-value <0.001). Prostate cancer with increased mtDNA content showed unfavorable pathologic characteristics including, higher disease stage (PT2 vs PT3 P-value = 0.018), extracapsular extension (P-value = 0.02) and a trend toward an increased Gleason score (P-value = 0.064). No significant association was observed between changes in mtDNA content and biochemical recurrence (median follow up of 107 months). Contrary to other cancer types, prostate cancer tissue shows no universally depleted mtDNA content. Rather, the change in mtDNA content is highly variable, mirroring known prostate cancer genome heterogeneity. Patients with high mtDNA content have an unfavorable pathology, while a high mtDNA content in normal adjacent prostate tissue is associated with worse prognosis. © 2017 Wiley Periodicals, Inc.

Collecting and Studying Blood and Tissue Samples From Patients With Locally Recurrent or Metastatic Prostate or Bladder/Urothelial Cancer

ClinicalTrials.gov

2017-12-04

Healthy Control; Localized Urothelial Carcinoma of the Renal Pelvis and Ureter; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Recurrent Bladder Carcinoma; Recurrent Prostate Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage IV Bladder Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Prostate Cancer

The predictive value of 2-year posttreatment biopsy after prostate cancer radiotherapy for eventual biochemical outcome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vance, Waseet; Tucker, Susan L.; Crevoisier, Renaud de

2007-03-01

Purpose: To determine the value of a 2-year post-radiotherapy (RT) prostate biopsy for predicting eventual biochemical failure in patients who were treated for localized prostate cancer. Methods and Materials: This study comprised 164 patients who underwent a planned 2-year post-RT prostate biopsy. The independent prognostic value of the biopsy results for forecasting eventual biochemical outcome and overall survival was tested with other factors (the Gleason score, 1992 American Joint Committee on Cancer tumor stage, pretreatment prostate-specific antigen level, risk group, and RT dose) in a multivariate analysis. The current nadir + 2 (CN + 2) definition of biochemical failure wasmore » used. Patients with rising prostate-specific antigen (PSA) or suspicious digital rectal examination before the biopsy were excluded. Results: The biopsy results were normal in 78 patients, scant atypical and malignant cells in 30, carcinoma with treatment effect in 43, and carcinoma without treatment effect in 13. Using the CN + 2 definition, we found a significant association between biopsy results and eventual biochemical failure. We also found that the biopsy status provides predictive information independent of the PSA status at the time of biopsy. Conclusion: A 2-year post-RT prostate biopsy may be useful for forecasting CN + 2 biochemical failure. Posttreatment prostate biopsy may be useful for identifying patients for aggressive salvage therapy.« less

Characterization of Desmoglein Expression in the Normal Prostatic Gland. Desmoglein 2 Is an Independent Prognostic Factor for Aggressive Prostate Cancer

PubMed Central

Barber, Alison G.; Castillo-Martin, Mireia; Bonal, Dennis M.; Rybicki, Benjamin A.; Christiano, Angela M.; Cordon-Cardo, Carlos

2014-01-01

Purpose The expression of desmogleins (DSGs), which are known to be crucial for establishing and maintaining the cell-cell adhesion required for tissue integrity, has been well characterized in the epidermis and hair follicle; however, their expression in other epithelial tissues such as prostate is poorly understood. Although downregulation of classical cadherins, such as E-cadherin, has been described in prostate cancer tissue samples, the expression of desmogleins has only been previously reported in prostate cancer cell lines. In this study we characterized desmoglein expression in normal prostate tissues, and further investigated whether Desmoglein 2 (DSG2) expression specifically can serve as a potential clinical prognostic factor for patients diagnosed with primary prostate cancer. Experimental Design We utilized immunofluorescence to examine DSG2 expression in normal prostate (n = 50) and in a clinically well-characterized cohort of prostate cancer patients (n = 414). Correlation of DSG2 expression with clinico-pathological characteristics and biochemical recurrence was analyzed to assess its clinical significance. Results These studies revealed that DSG2 and DSG4 were specifically expressed in prostatic luminal cells, whereas basal cells lack their expression. In contrast, DSG1 and DSG3 were not expressed in normal prostate epithelium. Further analyses of DSG2 expression in prostate cancer revealed that reduced levels of this biomarker were a significant independent marker of poor clinical outcome. Conclusion Here we report for the first time that a low DSG2 expression phenotype is a useful prognostic biomarker of tumor aggressiveness and may serve as an aid in identifying patients with clinically significant prostate cancer. PMID:24896103

PSMA PET and radionuclide therapy in prostate cancer

PubMed Central

Bouchelouche, Kirsten; Turkbey, Baris; Choyke, Peter L.

2016-01-01

Prostate cancer (Pca) is the most common malignancy in men and a major cause of cancer death. Accurate imaging plays an important role in diagnosis, staging, restaging, detection of biochemical recurrence, and for therapy of PCa patients. Since no effective treatment is available for advanced PCa, there is an urgent need to develop new and more effective therapeutic strategies. In order to optimize treatment outcome, especially in high risk PCa patients, therapy of PCa is moving rapidly towards personalization. Medical imaging, including positron emission tomography (PET)/computed tomography (CT), plays an important role in personalized medicine in oncology. In the recent years, much focus has been on prostate specific membrane antigen (PSMA) as a promising target for imaging and therapy with radionuclides, since it is upregulated in most PCa. In the prostate, one potential role for PSMA PET imaging is to help guiding focal therapy. Several studies have shown great potential of PSMA PET/CT for initial staging, lymph node staging, and detection of recurrence of PCa, even at very low PSA values after primary therapy. Furthermore, studies have shown that PSMA PET/CT has a higher detection rate than choline PET/CT. Radiolabeled PSMA ligands for therapy show promise in several studies with metastatic PCa, and is an area of active investigation. The “Image and treat” strategy, with radiolabeled PSMA ligands, has the potential to improve the treatment outcome of PCa patients, and is paving the way for precision medicine in PCa. The aim of this review is to give an overview of recent advancement in PSMA PET and radionuclide therapy of PCa. PMID:27825432

Estimation of radiation dosimetry for 68Ga-HBED-CC (PSMA-11) in patients with suspected recurrence of prostate cancer.

PubMed

Green, Mark A; Eitel, Jacob A; Fletcher, James W; Mathias, Carla J; Tann, Mark A; Gardner, Thomas; Koch, Michael O; Territo, Wendy; Polson, Heather; Hutchins, Gary D

2017-03-01

This study was performed to estimate the human radiation dosimetry for [ 68 Ga]Ga-HBED-CC (PSMA-11) ( 68 Ga PSMA-11). Under an RDRC-approved research protocol, we evaluated the biodistribution and pharmacokinetics of 68 Ga PSMA-11 with serial PET imaging following intravenous administration to nine prostate cancer patients in whom clinical [ 11 C]acetate PET/CT exams had been independently performed under Expanded Access IND 118,204. List-mode imaging was performed over the initial 0-10min post-injection with the pelvis in the field-of-view. Whole-body images were acquired, pelvis-to-head, at 15, 60, and 90-min post-injection. Additional images of the pelvis were acquired at 40-min and 115-min, and voided urine collected from each subject at 48-min and 120-min post-injection. Radiation dosimetry estimates were calculated from these data using the OLINDA software package. Renal uptake was high and relatively invariant, ranging from 11% to 14% of the injected dose between 15 and 90-min post-injection. Radioactivity collected in the voided urine accounted for 14% of the injected dose over a period of 120-min. Lymph nodes and skeletal metastases suspicious for prostate cancer recurrence were detected in a greater number of patients using 68 Ga PSMA-11 than using 11 C-acetate. Kidneys are the critical organ following 68 Ga PSMA-11 administration, receiving an estimated dose of 0.413mGy/MBq. This study confirms that the kidneys will be the critical organ following intravenous administration of 68 Ga PSMA-11, and provided data consistent with the expectation that 68 Ga PSMA-11 will be superior to [ 11 C]acetate for defining sites of recurrence in prostate cancer patients presenting with biochemical relapse. Copyright © 2016 Elsevier Inc. All rights reserved.

Patient-Level DNA Damage and Repair Pathway Profiles and Prognosis After Prostatectomy for High-Risk Prostate Cancer.

PubMed

Evans, Joseph R; Zhao, Shuang G; Chang, S Laura; Tomlins, Scott A; Erho, Nicholas; Sboner, Andrea; Schiewer, Matthew J; Spratt, Daniel E; Kothari, Vishal; Klein, Eric A; Den, Robert B; Dicker, Adam P; Karnes, R Jeffrey; Yu, Xiaochun; Nguyen, Paul L; Rubin, Mark A; de Bono, Johann; Knudsen, Karen E; Davicioni, Elai; Feng, Felix Y

2016-04-01

A substantial number of patients diagnosed with high-risk prostate cancer are at risk for metastatic progression after primary treatment. Better biomarkers are needed to identify patients at the highest risk to guide therapy intensification. To create a DNA damage and repair (DDR) pathway profiling method for use as a prognostic signature biomarker in high-risk prostate cancer. A cohort of 1090 patients with high-risk prostate cancer who underwent prostatectomy and were treated at 3 different academic institutions were divided into a training cohort (n = 545) and 3 pooled validation cohorts (n = 232, 130, and 183) assembled for case-control or case-cohort studies. Profiling of 9 DDR pathways using 17 gene sets for GSEA (Gene Set Enrichment Analysis) of high-density microarray gene expression data from formalin-fixed paraffin-embedded prostatectomy samples with median 10.3 years follow-up was performed. Prognostic signature development from DDR pathway profiles was studied, and DDR pathway gene mutation in published cohorts was analyzed. Biochemical recurrence-free, metastasis-free, and overall survival. Across the training cohort and pooled validation cohorts, 1090 men were studied; mean (SD) age at diagnosis was 65.3 (6.4) years. We found that there are distinct clusters of DDR pathways within the cohort, and DDR pathway enrichment is only weakly correlated with clinical variables such as age (Spearman ρ [ρ], range, -0.07 to 0.24), Gleason score (ρ, range, 0.03 to 0.20), prostate-specific antigen level (ρ, range, -0.07 to 0.10), while 13 of 17 DDR gene sets are strongly correlated with androgen receptor pathway enrichment (ρ, range, 0.33 to 0.82). In published cohorts, DDR pathway genes are rarely mutated. A DDR pathway profile prognostic signature built in the training cohort was significantly associated with biochemical recurrence-free, metastasis-free, and overall survival in the pooled validation cohorts independent of standard clinicopathological variables. The prognostic performance of the signature for metastasis-free survival appears to be stronger in the younger patients (HR, 1.67; 95% CI, 1.12-2.50) than in the older patients (HR, 0.77; 95% CI, 0.29-2.07) on multivariate Cox analysis. DNA damage and repair pathway profiling revealed patient-level variations and the DDR pathways are rarely affected by mutation. A DDR pathway signature showed strong prognostic performance with the long-term outcomes of metastasis-free and overall survival that may be useful for risk stratification of high-risk prostate cancer patients.

Role of imaging and biopsy to assess local recurrence after definitive treatment for prostate carcinoma (surgery, radiotherapy, cryotherapy, HIFU).

PubMed

Martino, Pasquale; Scattoni, Vincenzo; Galosi, Andrea B; Consonni, Paolo; Trombetta, Carlo; Palazzo, Silvano; Maccagnano, Carmen; Liguori, Giovanni; Valentino, Massimo; Battaglia, Michele; Barozzi, Libero

2011-10-01

Defining the site of recurrent disease early after definitive treatment for a localized prostate cancer is a critical issue as it may greatly influence the subsequent therapeutic strategy or patient management. A systematic review of the literature was performed by searching Medline from January 1995 up to January 2011. Electronic searches were limited to the English language, and the keywords prostate cancer, radiotherapy [RT], high intensity focused ultrasound [HIFU], cryotherapy [CRIO], transrectal ultrasound [TRUS], magnetic resonance [MRI], PET/TC, and prostate biopsy were used. Despite the fact that diagnosis of a local recurrence is based on PSA values and kinetics, imaging by means of different techniques may be a prerequisite for effective disease management. Unfortunately, prostate cancer local recurrences are very difficult to detect by TRUS and conventional imaging that have shown limited accuracy at least at early stages. On the contrary, functional and molecular imaging such as dynamic contrast-enhanced MRI (DCE-MRI), and diffusion-weighted imaging (DWI), offers the possibility of imaging molecular or cellular processes of individual tumors. Recently, PET/CT, using 11C-choline, 18F-fluorocholine or 11C-acetate has been successfully proposed in detecting local recurrences as well as distant metastases. Nevertheless, in controversial cases, it is necessary to perform a biopsy of the prostatic fossa or a biopsy of the prostate to assess the presence of a local recurrence under guidance of MRI or TRUS findings. It is likely that imaging will be extensively used in the future to detect and localize prostate cancer local recurrences before salvage treatment.

Nanoparticle Albumin-Bound Rapamycin in Treating Patients With Advanced Cancer With mTOR Mutations

ClinicalTrials.gov

2018-06-01

Advanced Malignant Neoplasm; Cervical Squamous Cell Carcinoma; Endometrial Carcinoma; Malignant Uterine Neoplasm; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Cervical Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Malignant Neoplasm; Recurrent Ovarian Carcinoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Solid Neoplasm; Stage III Bladder Cancer; Stage III Prostate Cancer; Stage III Renal Cell Cancer; Stage IIIA Breast Cancer; Stage IIIA Cervical Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Breast Cancer; Stage IIIB Cervical Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Breast Cancer; Stage IIIC Ovarian Cancer; Stage IV Breast Cancer; Stage IV Ovarian Cancer; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IVA Bladder Cancer; Stage IVA Cervical Cancer; Stage IVB Bladder Cancer; Stage IVB Cervical Cancer

A new imaging technique to detect recurrent prostate cancer is tested in new clinical trial | Center for Cancer Research

Cancer.gov

Standard imaging techniques cannot accurately locate sites of prostate cancer metastasis. The use of 18F-DCFPyL, a second-generation PET agent, aims to improve doctors’ ability to assess high-risk primary tumors, detect sites of recurrent prostate cancer and target therapies to specific sites of recurrence. Read more...

Reirradiation of Prostate Cancer Local Failures After Previous Curative Radiation Therapy: Long-Term Outcome and Tolerance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zilli, Thomas, E-mail: Thomas.Zilli@hcuge.ch; Faculty of Medicine, Geneva University, Geneva; Benz, Eileen

2016-10-01

Purpose: To evaluate the safety, feasibility, side-effect profile, and proof of concept of external beam radiation therapy (EBRT) with or without a brachytherapy (BT) boost for salvage of exclusive local failure after primary EBRT for prostate cancer. Methods and Materials: Fourteen patients with presumed exclusive local recurrence after primary EBRT with or without BT were considered eligible for reirradiation. The median normalized total dose in 2-Gy fractions (NTD{sub 2Gy}, α/β ratio = 1.5 Gy) was 74 Gy (range, 66-98.4 Gy) at first irradiation. Median time between the first irradiation and the reirradiation was 6.1 years (range, 4.7-10.2 years). Results: Between 2003 and 2008 salvage treatment was deliveredmore » with a median NTD{sub 2Gy} of 85.1 Gy (range, 70-93.4) to the prostate with EBRT with (n=10) or without (n=4) BT. Androgen deprivation was given to 12 patients (median time of 12 months). No grade ≥3 toxicity was observed during and within 6 weeks after RT. After a median follow-up of 94 months (range, 48-172 months) after salvage RT, 5-year grade ≥3 genitourinary and gastrointestinal toxicity-free survival figures were 77.9% ± 11.3% and 57.1% ± 13.2%, respectively. Four patients presented with combined grade 4 genitourinary/gastrointestinal toxicity. The 5-year biochemical relapse-free, local relapse-free, distant metastasis-free, and cancer-specific survival rates were 35.7% ± 12.8%, 50.0% ± 13.4%, 85.7% ± 9.4%, and 100%, respectively. Conclusion: Salvage whole-gland reirradiation for patients with a suspicion of exclusive local recurrence after initial RT may be associated with a high rate of severe radiation-induced side effects and poor long-term biochemical and local control.« less

Short (≤ 1 mm) positive surgical margin and risk of biochemical recurrence after radical prostatectomy.

PubMed

Shikanov, Sergey; Marchetti, Pablo; Desai, Vikas; Razmaria, Aria; Antic, Tatjana; Al-Ahmadie, Hikmat; Zagaja, Gregory; Eggener, Scott; Brendler, Charles; Shalhav, Arieh

2013-04-01

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: It has been suggested that a very short positive margin does not confer additional risk of BCR after radical prostatectomy. This study shows that even very short PSM is associated with increased risk of BCR. To re-evaluate, in a larger cohort with longer follow-up, our previously reported finding that a positive surgical margin (PSM) ≤ 1 mm may not confer an additional risk for biochemical recurrence (BCR) compared with a negative surgical margin (NSM). Margin status and length were evaluated in 2866 men treated with radical prostatectomy (RP) for clinically localized prostate cancer at our institution from 1994 to 2009. We compared the BCR-free survival probability of men with NSMs, a PSM ≤ 1 mm, and a PSM < 1 mm using the Kaplan-Meier method and a Cox regression model adjusted for preoperative prostate-specific antigen (PSA) level, age, pathological stage and pathological Gleason score (GS). Compared with a NSM, a PSM ≤ 1 mm was associated with 17% lower 3-year BCR-free survival for men with pT3 and GS ≥ 7 tumours and a 6% lower 3-year BCR-free survival for men with pT2 and GS ≤ 6 tumours (log-rank P < 0.001 for all). In the multivariate model, a PSM ≤ 1 mm was associated with a probability of BCR twice as high as that for a NSM (hazard ratio [HR] 2.2), as were a higher PSA level (HR 1.04), higher pathological stage (HR 2.7) and higher pathological GS (HR 3.7 [all P < 0.001]). In men with non-organ-confined or high grade prostate cancer, a PSM ≤ 1 mm has a significant adverse impact on BCR rates. © 2012 The Authors. BJU International © 2012 BJU International.

Comparison Between 64Cu-PSMA-617 PET/CT and 18F-Choline PET/CT Imaging in Early Diagnosis of Prostate Cancer Biochemical Recurrence.

PubMed

Cantiello, Francesco; Crocerossa, Fabio; Russo, Giorgio Ivan; Gangemi, Vincenzo; Ferro, Matteo; Vartolomei, Mihai Dorin; Lucarelli, Giuseppe; Mirabelli, Maria; Scafuro, Chiara; Ucciero, Giuseppe; De Cobelli, Ottavio; Morgia, Giuseppe; Damiano, Rocco; Cascini, Giuseppe Lucio

2018-06-04

To evaluate the diagnostic performance of 64 Cu-PSMA-617 positron emission tomography (PET) with computed tomography (CT) for restaging prostate cancer after biochemical recurrence (BCR) and to compare it with 18 F-choline PET/CT in a per-patient analysis. An observational study was performed of 43 patients with BCR after laparoscopic radical prostatectomy who underwent 64 Cu-PSMA-617 PET/CT and subsequently 18 F-choline PET/CT for restaging. The detection rates (DR) of 64 Cu-PSMA-617 PET/CT and of 18 F-choline PET/CT were calculated by standardized maximum uptake value (SUV max ) at 4 hours and SUV max at 1 hour as reference, respectively. Furthermore, univariate logistic regression analysis was carried out to identify independent predictive factors of positivity with 64 Cu-PSMA-617 PET/CT. An overall positivity with 64 Cu-PSMA-617 PET/CT was found in 32 patients (74.4%) versus 19 (44.2%) with 18 F-choline PET/CT. Specifically, after stratifying for prostate-specific antigen (PSA) values, we found a good performance of 64 Cu-PSMA-617 PET/CT at low PSA levels compared to 18 F-choline PET/CT, with a DR of 57.1% versus 14.3% for PSA 0.2-0.5 ng/mL (P = .031), and of 60% versus 30% with PSA 0.5-1 ng/mL. At univariate binary logistic regression analysis, PSA level was the only independent predictor of 64 Cu-PSMA-617 PET/CT positivity. No significant difference in terms of DR for both 64 Cu-PSMA-617 PET/CT and 18 F-choline PET/CT was found according to different Gleason score subgroups. In our study cohort, a better performance was observed for 64 Cu-PSMA-617 PET/CT compared to 18 F-choline PET/CT in restaging after BCR, especially in patients with low PSA values. Copyright © 2018 Elsevier Inc. All rights reserved.

PD-L1 promoter methylation is a prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy.

PubMed

Gevensleben, Heidrun; Holmes, Emily Eva; Goltz, Diane; Dietrich, Jörn; Sailer, Verena; Ellinger, Jörg; Dietrich, Dimo; Kristiansen, Glen

2016-11-29

The rapid development of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors has generated an urgent need for biomarkers assisting the selection of patients eligible for therapy. The use of PD-L1 immunohistochemistry, which has been suggested as a predictive biomarker, however, is confounded by multiple unresolved issues. The aim of this study therefore was to quantify PD-L1 DNA methylation (mPD-L1) in prostate tissue samples and to evaluate its potential as a biomarker in prostate cancer (PCa). In the training cohort, normal tissue showed significantly lower levels of mPD-L1 compared to tumor tissue. High mPD-L1 in PCa was associated with biochemical recurrence (BCR) in univariate Cox proportional hazards (hazard ratio (HR)=2.60 [95%CI: 1.50-4.51], p=0.001) and Kaplan-Meier analyses (p<0.001). These results were corroborated in an independent validation cohort in univariate Cox (HR=1.24 [95%CI: 1.08-1.43], p=0.002) and Kaplan-Meier analyses (p=0.029). Although mPD-L1 and PD-L1 protein expression did not correlate in the validation cohort, both parameters added significant prognostic information in bivariate Cox analysis (HR=1.22 [95%CI: 1.05-1.42], p=0.008 for mPD-L1 and HR=2.58 [95%CI: 1.43-4.63], p=0.002 for PD-L1 protein expression). mPD-L1 was analyzed in a training cohort from The Cancer Genome Atlas (n=498) and was subsequently measured in an independent validation cohort (n=299) by quantitative methylation-specific real-time PCR. All patients had undergone radical prostatectomy. mPD-L1 is a promising biomarker for the risk stratification of PCa patients and might offer additional relevant prognostic information to the implemented clinical parameters, particularly in the setting of immune checkpoint inhibition.

Conventional Versus Automated Implantation of Loose Seeds in Prostate Brachytherapy: Analysis of Dosimetric and Clinical Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Genebes, Caroline, E-mail: genebes.caroline@claudiusregaud.fr; Filleron, Thomas; Graff, Pierre

2013-11-15

Purpose: To review the clinical outcome of I-125 permanent prostate brachytherapy (PPB) for low-risk and intermediate-risk prostate cancer and to compare 2 techniques of loose-seed implantation. Methods and Materials: 574 consecutive patients underwent I-125 PPB for low-risk and intermediate-risk prostate cancer between 2000 and 2008. Two successive techniques were used: conventional implantation from 2000 to 2004 and automated implantation (Nucletron, FIRST system) from 2004 to 2008. Dosimetric and biochemical recurrence-free (bNED) survival results were reported and compared for the 2 techniques. Univariate and multivariate analysis researched independent predictors for bNED survival. Results: 419 (73%) and 155 (27%) patients with low-riskmore » and intermediate-risk disease, respectively, were treated (median follow-up time, 69.3 months). The 60-month bNED survival rates were 95.2% and 85.7%, respectively, for patients with low-risk and intermediate-risk disease (P=.04). In univariate analysis, patients treated with automated implantation had worse bNED survival rates than did those treated with conventional implantation (P<.0001). By day 30, patients treated with automated implantation showed lower values of dose delivered to 90% of prostate volume (D90) and volume of prostate receiving 100% of prescribed dose (V100). In multivariate analysis, implantation technique, Gleason score, and V100 on day 30 were independent predictors of recurrence-free status. Grade 3 urethritis and urinary incontinence were observed in 2.6% and 1.6% of the cohort, respectively, with no significant differences between the 2 techniques. No grade 3 proctitis was observed. Conclusion: Satisfactory 60-month bNED survival rates (93.1%) and acceptable toxicity (grade 3 urethritis <3%) were achieved by loose-seed implantation. Automated implantation was associated with worse dosimetric and bNED survival outcomes.« less

Nodal Clearance Rate and Long-Term Efficacy of Individualized Sentinel Node–Based Pelvic Intensity Modulated Radiation Therapy for High-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Müller, Arndt-Christian, E-mail: arndt-christian.mueller@med.uni-tuebingen.de; Eckert, Franziska; Paulsen, Frank

2016-02-01

Purpose: To assess the efficacy of individual sentinel node (SN)-guided pelvic intensity modulated radiation therapy (IMRT) by determining nodal clearance rate [(n expected nodal involvement − n observed regional recurrences)/n expected nodal involvement] in comparison with surgically staged patients. Methods and Materials: Data on 475 high-risk prostate cancer patients were examined. Sixty-one consecutive patients received pelvic SN-based IMRT (5 × 1.8 Gy/wk to 50.4 Gy [pelvic nodes + individual SN] and an integrated boost with 5 × 2.0 Gy/wk to 70.0 Gy to prostate + [base of] seminal vesicles) and neo-/adjuvant long-term androgen deprivation therapy; 414 patients after SN–pelvic lymph node dissection were used to calculate the expected nodal involvement rate for the radiation therapymore » sample. Biochemical control and overall survival were estimated for the SN-IMRT patients using the Kaplan-Meier method. The expected frequency of nodal involvement in the radiation therapy group was estimated by imputing frequencies of node-positive patients in the surgical sample to the pattern of Gleason, prostate-specific antigen, and T category in the radiation therapy sample. Results: After a median follow-up of 61 months, 5-year OS after SN-guided IMRT reached 84.4%. Biochemical control according to the Phoenix definition was 73.8%. The nodal clearance rate of SN-IMRT reached 94%. Retrospective follow-up evaluation is the main limitation. Conclusions: Radiation treatment of pelvic nodes individualized by inclusion of SNs is an effective regional treatment modality in high-risk prostate cancer patients. The pattern of relapse indicates that the SN-based target volume concept correctly covers individual pelvic nodes. Thus, this SN-based approach justifies further evaluation, including current dose-escalation strategies to the prostate in a larger prospective series.« less

Differentiation among prostate cancer patients with Gleason score of 7 using histopathology whole-slide image and genomic data

NASA Astrophysics Data System (ADS)

Ren, Jian; Karagoz, Kubra; Gatza, Michael; Foran, David J.; Qi, Xin

2018-03-01

Prostate cancer is the most common non-skin related cancer affecting 1 in 7 men in the United States. Treatment of patients with prostate cancer still remains a difficult decision-making process that requires physicians to balance clinical benefits, life expectancy, comorbidities, and treatment-related side effects. Gleason score (a sum of the primary and secondary Gleason patterns) solely based on morphological prostate glandular architecture has shown as one of the best predictors of prostate cancer outcome. Significant progress has been made on molecular subtyping prostate cancer delineated through the increasing use of gene sequencing. Prostate cancer patients with Gleason score of 7 show heterogeneity in recurrence and survival outcomes. Therefore, we propose to assess the correlation between histopathology images and genomic data with disease recurrence in prostate tumors with a Gleason 7 score to identify prognostic markers. In the study, we identify image biomarkers within tissue WSIs by modeling the spatial relationship from automatically created patches as a sequence within WSI by adopting a recurrence network model, namely long short-term memory (LSTM). Our preliminary results demonstrate that integrating image biomarkers from CNN with LSTM and genomic pathway scores, is more strongly correlated with patients recurrence of disease compared to standard clinical markers and engineered image texture features. The study further demonstrates that prostate cancer patients with Gleason score of 4+3 have a higher risk of disease progression and recurrence compared to prostate cancer patients with Gleason score of 3+4.

Tertiary Gleason patterns and biochemical recurrence after prostatectomy: proposal for a modified Gleason scoring system.

PubMed

Trock, Bruce J; Guo, Charles C; Gonzalgo, Mark L; Magheli, Ahmed; Loeb, Stacy; Epstein, Jonathan I

2009-10-01

We investigated the relationship between the tertiary Gleason component in radical prostatectomy specimens and biochemical recurrence in what is to our knowledge the largest single institution cohort to date. We evaluated data on 3,230 men who underwent radical prostatectomy at our institution from 2000 to 2005. Tertiary Gleason component was defined as Gleason grade pattern 4 or greater for Gleason score 6 and Gleason grade pattern 5 for Gleason score 7 or 8. Biochemical recurrence curves for cancer with tertiary Gleason component were intermediate between those of cancer without a tertiary Gleason component in the same Gleason score category and cancer in the next higher Gleason score category. The only exception was that Gleason score 4 + 3 = 7 with a tertiary Gleason component behaved like Gleason score 8. The tertiary Gleason component independently predicted recurrence when factoring in radical prostatectomy Gleason score, radical prostatectomy stage and prostate specific antigen (HR 1.45, p = 0.029). Furthermore, the magnitude of the tertiary Gleason component effect on recurrence did not differ by Gleason score category (p = 0.593). Although the tertiary Gleason component is frequently included in pathology reports, it is routinely omitted in other situations, such as predictive nomograms, research studies and patient counseling. The current study adds to a growing body of evidence highlighting the importance of the tertiary Gleason component in radical prostatectomy specimens. Accordingly consideration should be given to a modified radical prostatectomy Gleason scoring system that incorporates tertiary Gleason component in intuitive fashion, including Gleason score 6, 6.5 (Gleason score 6 with tertiary Gleason component), 7 (Gleason score 3 + 4 = 7), 7.25 (Gleason score 3 + 4 = 7 with tertiary Gleason component), 7.5 (Gleason score 4 + 3), 8 (Gleason score 4 + 3 with tertiary Gleason component or Gleason score 8), 8.5 (Gleason score 8 with tertiary Gleason component), 9 (Gleason score 4 + 5 or 5 + 4) and 10.

Towards intraoperative surgical margin assessment and visualization using bioimpedance properties of the tissue

NASA Astrophysics Data System (ADS)

Khan, Shadab; Mahara, Aditya; Hyams, Elias S.; Schned, Alan; Halter, Ryan

2015-03-01

Prostate cancer (PCa) has a high 10-year recurrence rate, making PCa the second leading cause of cancer-specific mortality among men in the USA. PCa recurrences are often predicted by assessing the status of surgical margins (SM) with positive surgical margins (PSM) increasing the chances of biochemical recurrence by 2-4 times. To this end, an SM assessment system using Electrical Impedance Spectroscopy (EIS) was developed with a microendoscopic probe. This system measures the tissue bioimpedance over a range of frequencies (1 kHz to 1MHz), and computes a Composite Impedance Metric (CIM). CIM can be used to classify tissue as benign or cancerous. The system was used to collect the impedance spectra from excised prostates, which were obtained from men undergoing radical prostatectomy. The data revealed statistically significant (p<0.05) differences in the impedance properties of the benign and tumorous tissues, and between different tissue morphologies. To visualize the results of SM-assessment, a visualization tool using da Vinci stereo laparoscope is being developed. Together with the visualization tool, the EIS-based SM assessment system can be potentially used to intraoperatively classify tissues and display the results on the surgical console with a video feed of the surgical site, thereby augmenting a surgeon's view of the site and providing a potential solution to the intraoperative SM assessment needs.

Salvage high-intensity focused ultrasound ablation for prostate cancer local recurrence after external-beam radiation therapy: prognostic value of prostate MRI.

PubMed

Rouvière, O; Sbihi, L; Gelet, A; Chapelon, J-Y

2013-07-01

To assess the prognostic value of magnetic resonance imaging (MRI) before salvage high-intensity focused ultrasound (HIFU) for locally recurrent prostate cancer after external-beam radiotherapy (EBRT). Forty-six patients who underwent prostate MRI before salvage HIFU for locally recurrent prostate cancer after EBRT were retrospectively studied. HIFU failure was defined as a prostate-specific antigen (PSA) value >nadir + 2 ng/ml (Phoenix criteria) or positive follow-up biopsy or initiation of any other salvage therapy. The following prognostic parameters were assessed: neoadjuvant hormone therapy, clinical stage and Gleason score of recurrence, PSA level and velocity at HIFU treatment, and six MRI-derived parameters (prostate volume, tumour volume, extracapsular extension, seminal vesicle invasion, tumour extension into the apex or anterior to the urethra). Two factors were significant independent predictors of salvage HIFU failure: the PSA level at HIFU treatment (p < 0.012; risk ratio: 1.15, 95% CI: 1.03-1.29) and the tumour extension anterior to the urethra, as assessed by MRI (p = 0.046, risk ratio: 2.51, 95% CI: 1.02-6.16). The location of cancer recurrence anterior to the urethra on MRI is an independent significant predictor of salvage HIFU failure for locally recurrent prostate cancer after EBRT. Therefore, MRI may be useful for patient selection before post-EBRT salvage HIFU ablation. Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Pathological Predictors for Site of Local Recurrence After Radiotherapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chopra, Supriya; Princess Margaret Hospital, University Health Network, Toronto; Toi, Ants

2012-03-01

Purpose: Rational design of targeted radiotherapy (RT) in prostate cancer (Pca) hinges on a better understanding of spatial patterns of recurrence. We sought to identify pathological factors predictive for site of local recurrence (LR) after external beam RT. Methods and Materials: Prospective databases were reviewed to identify men with LR after RT from 1997 through 2009. Patients with biochemical failure and biopsy-confirmed Pca more than 2 years after RT were evaluated. Prediction for site of recurrence based on the following pretreatment factors was determined on independent and cluster-sextant basis: presence of malignancy, dominant vs. nondominant percentage core length (PCL) involvement,more » PCL {>=} or <40%, and Gleason score. Sites of dominant PCL were defined as sextants with peak PCL involvement minus 10%, and >5% for each patient. Results: Forty-one patients with low-intermediate risk Pca constituted the study cohort. Median time to biopsy after RT was 51 months (range, 24-145). Of 246 sextants, 74 were involved with tumor at baseline. When sextants are treated as independent observations the presence of malignancy (77% vs. 22%, p = 0.0001), dominant PCL (90% vs. 46%, p = 0.0001), and PCL {>=}40% (89% vs. 68 %, p = 0.04) were found to be significant predictors for LR, although PCL {>=}40% did not retain statistical significance if sextants were considered correlated. The vast majority of patients (95%) recurred at the original site of dominant PCL or PCL {>=}40%, and 44% also recurred in regions of nondominant PCL <40% (n = 8) and/or benign sampling (n = 14) at baseline. Conclusions: LR after RT predominantly occurs in regions bearing higher histological tumor burden but are not isolated to these sites. Our data highlights the value of spatially resolved baseline pathological sampling and may assist in the design of clinical trials tailoring RT dose prescriptions to subregions of the prostate gland.« less

Cryotherapy for primary treatment of prostate cancer: intermediate term results of a prospective study from a single institution.

PubMed

Rodríguez, S Alvarez; Arias Fúnez, F; Bueno Bravo, C; Rodríguez-Patrón Rodríguez, R; Sanz Mayayo, E; Palacios, V Hevia; Burgos Revilla, F J

2014-01-01

Purpose. Published data about cryotherapy for prostate cancer (PC) treatment are based on case series with a lack of clinical trials and the inexistence of a validated definition of biochemical failure. A prospective study with standardized followup protocol was conducted in our institution. Material and Methods. Prospective study of a series of cases including 108 patients diagnosed with localized PC at clinical stage T1c-T2c treated by primary cryoablation and median followup of 61 months. Criteria of biochemical recurrence were unified according to the American Society for Therapeutic Radiology and Oncology (ASTRO). End points were biochemical progression-free survival (BPFS), cancer-specific survival, and overall survival. Rate of complications was reported. Results. The BPFS for low-, medium-, and high-risk patients was 96.4%, 91.2%, and 62.2%, respectively. Cancer-specific survival was 98.1%. Overall survival reached 94.4%. Complications included incontinence in 5.6%, urinary tract obstruction in 1.9%, urethral sloughing in 5.6%, haematuria in 1.9%, perineal pain in 11.1%, and prostatorectal fistula in 0.9%. Erectile disfunction was found in 98.1%. Conclusions. Cryotherapy is an effective and minimally invasive treatment for primary PC in well-selected cases, with low surgical risk and good results in terms of BPFS, cancer-specific survival, and overall survival.

Cryotherapy for Primary Treatment of Prostate Cancer: Intermediate Term Results of a Prospective Study from a Single Institution

PubMed Central

Rodríguez, S. Alvarez; Arias Fúnez, F.; Bueno Bravo, C.; Rodríguez-Patrón Rodríguez, R.; Sanz Mayayo, E.; Palacios, V. Hevia; Burgos Revilla, F. J.

2014-01-01

Purpose. Published data about cryotherapy for prostate cancer (PC) treatment are based on case series with a lack of clinical trials and the inexistence of a validated definition of biochemical failure. A prospective study with standardized followup protocol was conducted in our institution. Material and Methods. Prospective study of a series of cases including 108 patients diagnosed with localized PC at clinical stage T1c-T2c treated by primary cryoablation and median followup of 61 months. Criteria of biochemical recurrence were unified according to the American Society for Therapeutic Radiology and Oncology (ASTRO). End points were biochemical progression-free survival (BPFS), cancer-specific survival, and overall survival. Rate of complications was reported. Results. The BPFS for low-, medium-, and high-risk patients was 96.4%, 91.2%, and 62.2%, respectively. Cancer-specific survival was 98.1%. Overall survival reached 94.4%. Complications included incontinence in 5.6%, urinary tract obstruction in 1.9%, urethral sloughing in 5.6%, haematuria in 1.9%, perineal pain in 11.1%, and prostatorectal fistula in 0.9%. Erectile disfunction was found in 98.1%. Conclusions. Cryotherapy is an effective and minimally invasive treatment for primary PC in well-selected cases, with low surgical risk and good results in terms of BPFS, cancer-specific survival, and overall survival. PMID:24693437

Could 68-Ga PSMA PET/CT become a new tool in the decision-making strategy of prostate cancer patients with biochemical recurrence of PSA after radical prostatectomy? A preliminary, monocentric series.

PubMed

De Bari, Berardino; Mazzola, Rosario; Aiello, Dario; Fersino, Sergio; Gregucci, Fabiana; Alongi, Pierpaolo; Nicodemo, Maurizio; Cavalleri, Stefano; Salgarello, Matteo; Alongi, Filippo

2018-04-23

To evaluate the impact of gallium68 PSMA-11 (HBED-CC)-PET/CT on decision-making strategy of patients with relapsing prostate cancer (PC) presenting a second biochemical relapse after radical prostatectomy (RP) and salvage RT or salvage androgen deprivation therapy (ADT). 40 patients were retrospectively analyzed. All of them had received prostatectomy. Thirteen out of 40 were addressed to gallium68 PSMA-11 (HBED-CC)-PET/CT for a biochemical relapse after RP, 14/40 after a salvage RT and 13/40 after salvage or adjuvant ADT. The PSA level ranged between 0.1 and 1.62 ng/ml (median value: 0.51 ng/ml). We studied the impact on the decision-making process of a multidisciplinary tumor board of additional data obtained from gallium68 PSMA-11 (HBED-CC)-PET/CT. Thirty-one out of 40 evaluated patients showed positive findings at gallium68 PSMA-11 (HBED-CC)-PET/CT (77.5%). Of them, five were positive in the prostatic bed, nine in the pelvic nodes, twelve in nodes outside the pelvis and eight at bone level. Nine patients presented two different sites of relapse (22.5%). Gallium68 PSMA-11 (HBED-CC)-PET/CT data changed the therapeutic approach in 28 patients (70%). Gallium68 PSMA-11 (HBED-CC)-PET/CT can be a useful tool in the restaging of post-RP, RT or ADT patients presenting biochemical relapse of PC and it could change the decision-making process in up of 70% of these patients. Prospective, larger series are needed to establish the correct role of this very promising tool in the staging and therapeutic approach of PC patients.

PSMA-Based [(18)F]DCFPyL PET/CT Is Superior to Conventional Imaging for Lesion Detection in Patients with Metastatic Prostate Cancer.

PubMed

Rowe, Steven P; Macura, Katarzyna J; Mena, Esther; Blackford, Amanda L; Nadal, Rosa; Antonarakis, Emmanuel S; Eisenberger, Mario; Carducci, Michael; Fan, Hong; Dannals, Robert F; Chen, Ying; Mease, Ronnie C; Szabo, Zsolt; Pomper, Martin G; Cho, Steve Y

2016-06-01

Current standard of care conventional imaging modalities (CIM) such as X-ray computed tomography (CT) and bone scan can be limited for detection of metastatic prostate cancer and therefore improved imaging methods are an unmet clinical need. We evaluated the utility of a novel second-generation low molecular weight radiofluorinated prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) radiotracer, [(18)F]DCFPyL, in patients with metastatic prostate cancer. Nine patients with suspected prostate cancer recurrence, eight with CIM evidence of metastatic prostate cancer and one with biochemical recurrence, were imaged with [(18)F]DCFPyL PET/CT. Eight of the patients had contemporaneous CIM for comparison. A lesion-by-lesion comparison of the detection of suspected sites of metastatic prostate cancer was carried out between PET and CIM. Statistical analysis for estimated proportions of inter-modality agreement for detection of metastatic disease was calculated accounting for intra-patient correlation using general estimating equation (GEE) intercept-only regression models. One hundred thirty-nine sites of PET positive [(18)F]DCFPyL uptake (138 definite, 1 equivocal) for metastatic disease were detected in the eight patients with available comparison CIM. By contrast, only 45 lesions were identified on CIM (30 definite, 15 equivocal). When lesions were negative or equivocal on CIM, it was estimated that a large portion of these lesions or 0.72 (95 % confidence interval (CI) 0.55-0.84) would be positive on [(18)F]DCFPyL PET. Conversely, of those lesions negative or equivocal on [(18)F]DCFPyL PET, it was estimated that only a very small proportion or 0.03 (95 % CI 0.01-0.07) would be positive on CIM. Delayed 2-h-post-injection time point PET yielded higher tumor radiotracer uptake and higher tumor-to-background ratios than an earlier 1-h-post-injection time point. A novel PSMA-targeted PET radiotracer, [(18)F]DCFPyL, was able to a large number of suspected sites of prostate cancer, many of which were occult or equivocal by CIM. This study provides strong preliminary evidence for the use of this second-generation PSMA-targeted PET radiotracer for detection of metastatic prostate cancer and lends further support for the importance of PSMA-targeted PET imaging in prostate cancer.

Prognostic Value of Protocadherin10 (PCDH10) Methylation in Serum of Prostate Cancer Patients.

PubMed

Deng, Qiu-Kui; Lei, Yong-Gang; Lin, Ying-Li; Ma, Jian-Guo; Li, Wen-Ping

2016-02-16

BACKGROUND Prostate cancer is a heterogeneous malignancy with outcome difficult to predict. Currently, there is an urgent need to identify novel biomarkers that can accurately predict patient outcome and improve the treatment strategy. The aim of this study was to investigate the methylation status of PCDH10 in serum of prostate cancer patients and its potential relevance to clinicopathological features and prognosis. MATERIAL AND METHODS The methylation status of PCDH10 in serum of 171 primary prostate cancer patients and 65 controls was evaluated by methylation-specific PCR (MSP), after which the relationship between PCDH10 methylation and clinicopathologic features was evaluated. Kaplan-Meier survival analysis and Cox analysis were used to evaluate the correlation between PCDH10 methylation and prognosis. RESULTS PCDH10 methylation occurred frequently in serum of prostate cancer patients. Moreover, PCDH10 methylation was significantly associated with higher preoperative PSA level, advanced clinical stage, higher Gleason score, lymph node metastasis, and biochemical recurrence (BCR). In addition, patients with methylated PCDH10 had shorter BCR-free survival and overall survival than patients with unmethylated PCDH10. Univariate and multivariate Cox proportional hazards model analysis indicated that PCDH10 methylation in serum is an independent predictor of worse BCR-free survival and overall survival. CONCLUSIONS PCDH10 methylation in serum is a potential prognostic biomarker for prostate cancer.

Pathologic implications of prostatic anterior fat pad.

PubMed

Jeong, Jeongyun; Choi, Eun Yong; Kang, Dong I; Ercolani, Matt; Lee, Dong Hyeon; Kim, Wun-Jae; Kim, Isaac Yi

2013-01-01

Lymph node status has significant pathologic implications in patients with prostate cancer. In this study, we have performed pathologic analysis of prostatic anterior fat pad (PAFP) excised during robot-assisted radical prostatectomy (RARP) to investigate the potential role of AFP on pathologic staging of prostate cancer. A total of 258 consecutive patients underwent PAFP excision during RARP between July 2007 and June 2009. PAFP was removed and submitted en bloc to the pathology department and evaluated for the presence of lymphoid tissue and metastatic prostate cancer. Retrospective chart review was performed for all patients. Of the 258 patients, 30 (11.6%) had 1 or 2 PAFP lymph nodes and 228 (88.4%) men showed no lymphoid tissue in their PAFPs. Preoperatively, mean PSA level was higher in the former group. There were no significant pathologic differences between the 2 groups. Among the 30 patients with PAFP lymph nodes, 3 were positive for metastatic prostate cancer. All 3 of these patients had high-risk features preoperatively. In 1 patient, the pelvic lymph nodes were negative for metastatic prostate cancer. At 2-year follow-up, PSA level of this patient was undetectable. Herein, we demonstrated that the PAFP contained lymph nodes in over 11% of the patients undergoing RARP at our institution. Prostate cancer was upstaged in 1 patient as a result of PAFP excision. Since this patient is free of biochemical recurrence at 2 years, routine excision and pathologic analysis of PAFP should be considered in prostate cancer patients undergoing radical prostatectomy. Copyright © 2013 Elsevier Inc. All rights reserved.

Proposed prognostic scoring system evaluating risk factors for biochemical recurrence of prostate cancer after salvage radiation therapy.

PubMed

Lee, Richard J; Tzou, Katherine S; Heckman, Michael G; Hobbs, Corey J; Rawal, Bhupendra; Diehl, Nancy N; Peterson, Jennifer L; Paryani, Nitesh N; Ko, Stephen J; Daugherty, Larry C; Vallow, Laura A; Wong, William; Schild, Steven; Pisansky, Thomas M; Buskirk, Steven J

2016-08-01

To update a previously proposed prognostic scoring system that predicts risk of biochemical recurrence (BCR) after salvage radiation therapy (SRT) for recurrent prostate cancer when using additional patients and a PSA value of 0.2 ng/mL and rising as the definition of BCR. We included 577 patients who received SRT for a rising PSA after radical prostatectomy in this retrospective cohort study. Clinical, pathological, and SRT characteristics were evaluated for association with BCR using relative risks (RRs) from multivariable Cox regression models. With a median follow-up of 5.5 years after SRT, 354 patients (61%) experienced BCR. At 5 years after SRT, 40% of patients were free of BCR. Independent associations with BCR were identified for the PSA level before SRT (RR [doubling]: 1.25, P < 0.001), pathological tumour stage (RR [T3a vs T2] 1.21, P = 0.19; RR [T3b/T4 vs T2] 2.09, P < 0.001; overall P < 0.001), Gleason score (RR [7 vs <7] 1.63, P < 0.001; RR [8-10 vs <7] 2.28, P < 0.001; overall P < 0.001), and surgical margin status (RR [positive vs negative] 0.71, P = 0.003). We combined these four variables to create a prognostic scoring system that predicted BCR risk with a c-index of 0.66. Scores ranged from 0 to 7, and 5-year freedom from BCR for different levels of the score was as follows: Score = 0-1: 66%, Score = 2: 46%, Score = 3: 28%, Score = 4: 19%, and Score = 5-7: 15%. We developed a scoring system that provides an estimation of the risk of BCR after SRT. These findings will be useful for patients and physicians in decision making for radiation therapy in the salvage setting. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

DNA methylation screening of primary prostate tumors identifies SRD5A2 and CYP11A1 as candidate markers for assessing risk of biochemical recurrence.

PubMed

Horning, Aaron M; Awe, Julius A; Wang, Chiou-Miin; Liu, Joseph; Lai, Zhao; Wang, Vickie Yao; Jadhav, Rohit R; Louie, Anna D; Lin, Chun-Lin; Kroczak, Tad; Chen, Yidong; Jin, Victor X; Abboud-Werner, Sherry L; Leach, Robin J; Hernandez, Javior; Thompson, Ian M; Saranchuk, Jeff; Drachenberg, Darrel; Chen, Chun-Liang; Mai, Sabine; Huang, Tim Hui-Ming

2015-11-01

Altered DNA methylation in CpG islands of gene promoters has been implicated in prostate cancer (PCa) progression and can be used to predict disease outcome. In this study, we determine whether methylation changes of androgen biosynthesis pathway (ABP)-related genes in patients' plasma cell-free DNA (cfDNA) can serve as prognostic markers for biochemical recurrence (BCR). Methyl-binding domain capture sequencing (MBDCap-seq) was used to identify differentially methylated regions (DMRs) in primary tumors of patients who subsequently developed BCR or not, respectively. Methylation pyrosequencing of candidate loci was validated in cfDNA samples of 86 PCa patients taken at and/or post-radical prostatectomy (RP) using univariate and multivariate prediction analyses. Putative DMRs in 13 of 30 ABP-related genes were found between tumors of BCR (n = 12) versus no evidence of disease (NED) (n = 15). In silico analysis of The Cancer Genome Atlas data confirmed increased DNA methylation of two loci-SRD5A2 and CYP11A1, which also correlated with their decreased expression, in tumors with subsequent BCR development. Their aberrant cfDNA methylation was also associated with detectable levels of PSA taken after patients' post-RP. Multivariate analysis of the change in cfDNA methylation at all of CpG sites measured along with patient's treatment history predicted if a patient will develop BCR with 77.5% overall accuracy. Overall, increased DNA methylation of SRD5A2 and CYP11A1 related to androgen biosynthesis functions may play a role in BCR after patients' RP. The correlation between aberrant cfDNA methylation and detectable PSA in post-RP further suggests their utility as predictive markers for PCa recurrence. . © 2015 Wiley Periodicals, Inc.

Adjuvant and Salvage Radiotherapy After Prostatectomy for Prostate Cancer: A Literature Review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pasquier, David; Ballereau, Charles

2008-11-15

Purpose: Given that postprostatectomy recurrence of prostate cancer occurs in 10-40% of patients, the best use of immediate postoperative radiotherapy (RT) in high-risk patients and salvage RT for biochemical recurrence remains a topic of debate. We assessed the levels of evidence (in terms of efficacy, prognostic factors, and toxicity) for the following treatment strategies: immediate postoperative RT alone, salvage RT alone, and the addition of androgen deprivation therapy to the two RT strategies. Methods and Materials: A systematic literature search for controlled randomized trials, noncontrolled trials, and retrospective studies between 1990 and 2008 was performed on PubMed, CancerLit, and MEDLINE.more » Only relevant articles that had appeared in peer-reviewed journals were selected. We report on the levels of evidence (according to the National Cancer Institute guidelines) supporting the various treatment strategies. Results: Immediate postoperative RT improves biochemical and clinical progression-free survival (Level of evidence, 1.ii) but has no significant effect on metastasis-free survival or overall survival. A pathologic review is of particular importance for correctly analyzing the treatment strategies. Low-grade morbidity has been significantly greater in the postoperative groups, but no severe toxicity has been observed. The influence of immediate postoperative RT on postprostatectomy continence appears to be slight; therefore, immediate postoperative RT should be considered in patients with major risk factors for local relapse (Level of evidence, 1.ii). On the basis of extensive retrospective data, salvage RT is effective in biochemical relapse after prostatectomy; some patients with few adverse prognostic factors might also benefit from salvage RT (Level of evidence, 3.ii). The addition of androgen deprivation therapy to immediate postoperative or salvage RT has only been supported by weak, retrospective data (Level of evidence, 3.ii). Conclusion: Prospective randomized trials are needed to compare immediate postoperative RT with salvage RT and to assess the value of androgen deprivation therapy in this setting.« less

Are all grade group 4 prostate cancers created equal? Implications for the applicability of the novel grade grouping.

PubMed

Gandaglia, Giorgio; Karnes, R Jeffrey; Sivaraman, Arjun; Moschini, Marco; Fossati, Nicola; Zaffuto, Emanuele; DellʼOglio, Paolo; Cathelineau, Xavier; Montorsi, Francesco; Sanchez-Salas, Rafael; Briganti, Alberto

2017-07-01

According to the novel prostate cancer (PCa) grade grouping, men with Gleason score 8 should be included in the grade group 4 regardless of primary and secondary scores. We aimed at evaluating the effect of Gleason patterns on the risk of recurrence in men with grade group 4 PCa. Overall, 1,089 patients treated with radical prostatectomy with grade group 4 PCa at final pathology were identified. Biochemical recurrence (BCR) was defined as 2 consecutive prostate-specific antigen values≥0.2ng/ml and rising. Clinical recurrence (CR) was defined as positive imaging after BCR. Kaplan-Meier analyses assessed time to BCR and CR. Multivariable Cox regression analyses assessed the impact of Gleason patterns on the risk of BCR and CR. Overall, 295 (27.1%), 651 (59.8%), and 143 (13.1%) patients had pathologic Gleason pattern 3+5, 4+4, and 5+3. Overall, 435 (39.9%) patients had positive margins and 439 (30.2%), 300 (27.5%), 350 (32.1%), and 216 (19.8%) had pT2, pT3a, pT3b/4, and pN1 disease. Median follow-up was 83 months. Overall, 536 and 221 patients experienced BCR and CR. The 10-year BCR- and CR-free survival rates were 42.9% and 67.5% vs. 38.3% and 59.7% vs. 40.6% and 50.4% for patients with pathologic Gleason pattern 3+5 vs. 4+4 vs. 5+3, respectively (all P≤0.005). In multivariable analyses, patients with Gleason pattern 3+5 were at lower risk of BCR compared to those with 4+4 (P = 0.002). Men with Gleason pattern 3+5 were at lower risk of CR compared to those with 4+4 and 5+3 (all P≤ 0.01). Patients with a primary Gleason score 3 are at reduced risk of recurrence as compared to their counterparts with 4 or 5. Primary and secondary Gleason scores should be considered to stratify the risk of recurrence after surgery in patients with grade group 4 PCa. Copyright © 2017 Elsevier Inc. All rights reserved.

68Ga-PSMA and 11C-Choline comparison using a tri-modality PET/CT-MRI (3.0 T) system with a dedicated shuttle.

PubMed

Alonso, Omar; Dos Santos, Gerardo; García Fontes, Margarita; Balter, Henia; Engler, Henry

2018-01-01

The aim of this study was to prospectively compare the detection rate of 68 Ga-PSMA versus 11 C-Choline in men with prostate cancer with biochemical recurrence and to demonstrate the added value of a tri-modality PET/CT-MRI system. We analysed 36 patients who underwent both 11 C-Choline PET/CT and 68 Ga-PSMA PET/CT scanning within a time window of 1-2 weeks. Additionally, for the 68 Ga-PSMA scan, we used a PET/CT-MRI (3.0 T) system with a dedicated shuttle, acquiring MRI images of the pelvis. Both scans were positive in 18 patients (50%) and negative in 8 patients (22%). Nine patients were positive with 68 Ga-PSMA alone (25%) and one with 11 C-Choline only (3%). The median detected lesion per patient was 2 for 68 Ga-PSMA (range 0-93) and 1 for 11 C-Choline (range 0-57). Tumour to background ratios in all concordant lesions ( n  = 96) were higher for 68 Ga-PSMA than for 11 C-Choline (110.3 ± 107.8 and 27.5 ± 17.1, mean ± S.D., for each tracer, respectively P  = 0.0001). The number of detected lesions per patient was higher for 11 C-Choline in those with PSA ≥ 3.3 ng/mL, while the number of detected lesions was independent of PSA levels for 68 Ga-PSMA using the same PSA cut-off value. Metastatic pelvic lesions were found in 25 patients (69%) with 68 Ga-PSMA PET/CT, in 18 (50%) with 11 C-Choline PET/CT and in 21 (58%) with MRI (3.0 T). MRI was very useful in detecting recurrence in cases classified as indeterminate by means of PET/CT alone at prostate bed. In patients with prostate cancer with biochemical recurrence 68 Ga-PSMA detected more lesions per patient than 11 C-Choline, regardless of PSA levels. PET/CT-MRI (3.0 T) system is a feasible imaging modality that potentially adds useful relevant information with increased accuracy of diagnosis.

A pretreatment nomogram for prediction of biochemical failure after primary cryoablation of the prostate.

PubMed

Elshafei, Ahmed; Kovac, Evan; Dhar, Nivedita; Levy, David; Polascik, Thomas; Mouraviev, Vladimir; Yu, Changhong; Jones, J Stephen

2015-09-01

To create a predictive nomogram for biochemical failure following primary whole-gland cryoablation of the prostate for localized prostate cancer (LPCa). We retrospectively analyzed 2,242 patients from the Cryo On-Line Database (COLD) who were treatment naive and had undergone primary whole gland cryoablation of the prostate for biopsy-confirmed LPCa. Kaplan-Meier (KM) curves estimating 5 year biochemical progression-free survival (bPFS) were generated. Multivariable Cox proportional hazards analysis (CoxPH) was performed in order to construct the nomogram. The nomogram was internally validated using the bootstrap technique. Overall, the KM estimated 5 year bPFS was 72.8%. Stratified by D'Amico risk, The KM estimated 5 year bPFS was 82.6%, 71.1%, and 57.8% for low-, intermediate-, and high-risk groups, respectively. Statistically significant predictors of biochemical outcomes from CoxPH analysis were pre-treatment prostate specific antigen (PTPSA) (P < 0.001), total prostate volume (P = 0.004), clinical stage (P = 0.034), and Gleason score (0.004). A nomogram for predicted 5 year biochemical progression free probability was constructed with a concordance index of 0.652. An online risk calculator was also generated. To the best of our knowledge, this is the first predictive nomogram for biochemical outcomes after primary whole gland cryoablation of the prostate using socio-demographic, pretreatment, clinical, and prostate biopsy data. Our nomogram and online risk calculator can guide both patients and urologists for shared decision making regarding definitive treatment options. © 2015 Wiley Periodicals, Inc.

Heterogeneity of DNA methylation in multifocal prostate cancer.

PubMed

Serenaite, Inga; Daniunaite, Kristina; Jankevicius, Feliksas; Laurinavicius, Arvydas; Petroska, Donatas; Lazutka, Juozas R; Jarmalaite, Sonata

2015-01-01

Most prostate cancer (PCa) cases are multifocal, and separate foci display histological and molecular heterogeneity. DNA hypermethylation is a frequent alteration in PCa, but interfocal heterogeneity of these changes has not been extensively investigated. Ten pairs of foci from multifocal PCa and 15 benign prostatic hyperplasia (BPH) samples were obtained from prostatectomy specimens, resulting altogether in 35 samples. Methylation-specific PCR (MSP) was used to evaluate methylation status of nine tumor suppressor genes (TSGs), and a set of selected TSGs was quantitatively analyzed for methylation intensity by pyrosequencing. Promoter sequences of the RASSF1 and ESR1 genes were methylated in all paired PCa foci, and frequent (≥75 %) DNA methylation was detected in RARB, GSTP1, and ABCB1 genes. MSP revealed different methylation status of at least one gene in separate foci in 8 out of 10 multifocal tumors. The mean methylation level of ESR1, GSTP1, RASSF1, and RARB differed between the paired foci of all PCa cases. The intensity of DNA methylation in these TSGs was significantly higher in PCa cases than in BPH (p < 0.001). Hierarchical cluster analysis revealed a divergent methylation profile of paired PCa foci, while the foci from separate cases with biochemical recurrence showed similar methylation profile and the highest mean levels of DNA methylation. Our findings suggest that PCa tissue is heterogeneous, as between paired foci differences in DNA methylation status were found. Common epigenetic profile of recurrent tumors can be inferred from our data.

Evidence That Selenium Binding Protein 1 Is a Tumor Suppressor in Prostate Cancer

PubMed Central

Ansong, Emmanuel; Ying, Qi; Ekoue, Dede N.; Deaton, Ryan; Hall, Andrew R.; Kajdacsy-Balla, Andre; Yang, Wancai; Gann, Peter H.; Diamond, Alan M.

2015-01-01

Selenium-Binding Protein 1 (SBP1, SELENBP1, hSP56) is a selenium-associated protein shown to be at lower levels in tumors, and its lower levels are frequently predictive of a poor clinical outcome. Distinguishing indolent from aggressive prostate cancer is a major challenge in disease management. Associations between SBP1 levels, tumor grade, and disease recurrence following prostatectomy were investigated by duplex immunofluorescence imaging using a tissue microarray containing tissue from 202 prostate cancer patients who experienced biochemical (PSA) recurrence after prostatectomy and 202 matched control patients whose cancer did not recur. Samples were matched by age, ethnicity, pathological stage and Gleason grade, and images were quantified using the Vectra multispectral imaging system. Fluorescent labels were targeted for SBP1 and cytokeratins 8/18 to restrict scoring to tumor cells, and cell-by-cell quantification of SBP1 in the nucleus and cytoplasm was performed. Nuclear SBP1 levels and the nuclear to cytoplasm ratio were inversely associated with tumor grade using linear regression analysis. Following classification of samples into quartiles based on the SBP1 levels among controls, tumors in the lowest quartile were more than twice as likely to recur compared to those in any other quartile. Inducible ectopic SBP1 expression reduced the ability of HCT-116 human tumor cells to grow in soft agar, a measure of transformation, without affecting proliferation. Cells expressing SBP1 also demonstrated a robust induction in the phosphorylation of the p53 tumor suppressor at serine 15. These data indicate that loss of SBP1 may play an independent contributing role in prostate cancer progression and its levels might be useful in distinguishing indolent from aggressive disease. PMID:25993660

Cabazitaxel Plus Prednisone With Octreotide For Castration-Resistant Prostate Cancer (CRPC) Previously Treated With Docetaxel

ClinicalTrials.gov

2014-11-21

Diarrhea; Hormone-resistant Prostate Cancer; Recurrent Prostate Cancer; Stage I Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage IV Prostate Cancer

Lack of an Association between Neutrophil-to-Lymphocyte Ratio and PSA Failure of Prostate Cancer Patients Who Underwent Radical Prostatectomy.

PubMed

Maeda, Yoko; Kawahara, Takashi; Koizumi, Mitsuyuki; Ito, Hiroki; Kumano, Yohei; Ohtaka, Mari; Kondo, Takuya; Mochizuki, Taku; Hattori, Yusuke; Teranishi, Jun-Ichi; Yumura, Yasushi; Miyoshi, Yasuhide; Yao, Masahiro; Miyamoto, Hiroshi; Uemura, Hiroji

2016-01-01

Introduction. The neutrophil-to-lymphocyte ratio (NLR), which can be easily calculated from routine complete blood counts of the peripheral blood, has been suggested to serve as a prognostic factor for some solid malignancies. In the present study, we aimed to determine the relationship between NLR in prostate cancer patients undergoing radical prostatectomy (RP) and their prognosis. Materials and Methods. We assessed NLR in 73 men (patients) who received RP for their prostate cancer. We also performed immunohistochemistry for CD8 and CD66b in a separate set of RP specimens. Results. The median NLR in the 73 patients was 1.85. There were no significant correlations of NLR with tumor grade (p = 0.834), pathological T stage (p = 0.082), lymph node metastasis (p = 0.062), or resection margin status (p = 0.772). Based on the area under the receiver operator characteristic curve (AUROC) to predict biochemical recurrence after RP, potential NLR cut-off point was determined to be 2.88 or 3.88. However, both of these cut-off points did not precisely predict the prognosis. There were no statistically significant differences in the number of CD66b-positive neutrophils or CD8-positive lymphocytes between stromal tissues adjacent to cancer glands and stromal tissues away from cancer glands and between different grades or stages of tumors. Conclusions. There was no association between NLR and biochemical failure after prostatectomy.

Pathological Outcome following Radical Prostatectomy in Men with Prostate Specific Antigen Greater than 10 ng/ml and Histologically Favorable Risk Prostate Cancer.

PubMed

Yu, Jiwoong; Kwon, Young Suk; Kim, Sinae; Han, Christopher Sejong; Farber, Nicholas; Kim, Jongmyung; Byun, Seok Soo; Kim, Wun-Jae; Jeon, Seong Soo; Kim, Isaac Yi

2016-05-01

Active surveillance is now the treatment of choice in men with low risk prostate cancer. Although there is no consensus on which patients are eligible for active surveillance, prostate specific antigen above 10 ng/ml is generally excluded. In an attempt to determine the validity of using a prostate specific antigen cutoff of 10 ng/ml to counsel men considering active surveillance we analyzed a multi-institution database to determine the pathological outcome in men with prostate specific antigen greater than 10 ng/ml but histologically favorable risk prostate cancer. We queried a prospectively maintained database of men with histologically favorable risk prostate cancer who underwent radical prostatectomy between 2003 and 2015. The cohort was categorized into 3 groups based on prostate specific antigen level, including low-less than 10 ng/ml, intermediate-10 or greater to less than 20 and high-20 or greater. Associations of prostate specific antigen group with adverse pathological and oncologic outcomes were analyzed. Of 2,125 patients 1,327 were categorized with histologically favorable risk disease. However on multivariate analyses the rates of up staging and upgrading were similar between the intermediate and low prostate specific antigen groups. In contrast compared to the intermediate prostate specific antigen group the high group had higher incidences of up staging (p = 0.02) and upgrading to 4 + 3 or greater disease (p = 0.046). Biochemical recurrence-free survival rates revealed no pairwise intergroup differences except between the low and high groups. Patients with preoperatively elevated prostate specific antigen between 10 and less than 20 ng/ml who otherwise had histologically favorable risk prostate cancer were not at higher risk for adverse pathological outcomes than men with prostate specific antigen less than 10 ng/ml. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Multiplex biomarker approach for determining risk of prostate-specific antigen-defined recurrence of prostate cancer.

PubMed

Rhodes, Daniel R; Sanda, Martin G; Otte, Arie P; Chinnaiyan, Arul M; Rubin, Mark A

2003-05-07

Molecular signatures in cancer tissue may be useful for diagnosis and are associated with survival. We used results from high-density tissue microarrays (TMAs) to define combinations of candidate biomarkers associated with the rate of prostate cancer progression after radical prostatectomy that could identify patients at high risk for recurrence. Fourteen candidate biomarkers for prostate cancer for which antibodies are available included hepsin, pim-1 kinase, E-cadherin (ECAD; cell adhesion molecule), alpha-methylacyl-coenzyme A racemase, and EZH2 (enhancer of zeste homolog 2, a transcriptional repressor). TMAs containing more than 2000 tumor samples from 259 patients who underwent radical prostatectomy for localized prostate cancer were studied with these antibodies. Immunohistochemistry results were evaluated in conjunction with clinical parameters associated with prostate cancer progression, including tumor stage, Gleason score, and prostate-specific antigen (PSA) level. Recurrence was defined as a postsurgery PSA level of more than 0.2 ng/mL. All statistical tests were two-sided. Moderate or strong expression of EZH2 coupled with at most moderate expression of ECAD (i.e., a positive EZH2:ECAD status) was the biomarker combination that was most strongly associated with the recurrence of prostate cancer. EZH2:ECAD status was statistically significantly associated with prostate cancer recurrence in a training set of 103 patients (relative risk [RR] = 2.52, 95% confidence interval [CI] = 1.09 to 5.81; P =.021), in a validation set of 80 patients (RR = 3.72, 95% CI = 1.27 to 10.91; P =.009), and in the combined set of 183 patients (RR = 2.96, 95% CI = 1.56 to 5.61; P<.001). EZH2:ECAD status was statistically significantly associated with disease recurrence even after adjusting for clinical parameters, such as tumor stage, Gleason score, and PSA level (hazard ratio = 3.19, 95% CI = 1.50 to 6.77; P =.003). EZH2:ECAD status was statistically significantly associated with prostate cancer recurrence after radical prostatectomy and may be useful in defining a cohort of high-risk patients.

Carbon-ion Radiotherapy for Prostate Cancer: Analysis of Morbidities and Change in Health-related Quality of Life.

PubMed

Ishikawa, Hitoshi; Katoh, Hiroyuki; Kaminuma, Takuya; Kawamura, Hidemasa; Ito, Kazuto; Matsui, Hiroshi; Hirato, Junko; Shimizu, Nobuaki; Takezawa, Yutaka; Tsuji, Hiroshi; Suzuki, Kazuhiro; Ohno, Tatsuya; Nakano, Takashi

2015-10-01

To prospectively evaluate the feasibility of carbon-ion radiotherapy (C-ion RT) for prostate cancer using a new compact-sized accelerator. Seventy-six patients underwent C-ion RT at our center using a recommended dose fractionation of 57.6 GyE in 16 fractions established at the National Institute of Radiological Sciences. Health-related Quality of Life (HRQOL) assessment was also performed using the Medical Outcome Study 8-items Short Form Health Survey (SF-8) questionnaire. The median follow-up time was 51 months (range=8-58 months). Grade 2 gastrointestinal and genitourinary complications developed in 1 (1.3%) and 5 (6.6%) patients, respectively. Recurrences occurred in 4 patients, and the 4-year biochemical relapse-free rate was 94.6%. The HRQOL scores after C-ion RT were objectively well-maintained. Irrespective of the small number of patients of the study, C-ion RT for prostate cancer using the first commercial-based accelerator reproduced the toxicity outcomes at the NIRS. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chronic bacterial prostatitis in men with spinal cord injury.

PubMed

Krebs, Jörg; Bartel, Peter; Pannek, Jürgen

2014-12-01

Recurrent urinary tract infections (UTI) are a major problem affecting spinal cord injury (SCI) patients and may stem from chronic bacterial prostatitis. We have therefore investigated the presence of chronic bacterial prostatitis and its role in the development of recurrent symptomatic UTI in SCI men. This study is a prospective cross-sectional investigation of bacterial prostatitis in SCI men in a single SCI rehabilitation center. In 50 men with chronic SCI presenting for a routine urologic examination, urine samples before and after prostate massage were taken for microbiologic investigation and white blood cell counting. Furthermore, patient characteristics, bladder diary details, and the annual rate of symptomatic UTI were collected retrospectively. No participant reported current symptoms of UTI or prostatitis. In most men (39/50, 78 %), the microbiologic analysis of the post-massage urine sample revealed growth of pathogenic bacteria. The majority of these men (32/39, 82 %) also presented with mostly (27/39, 69 %) the same pathogenic bacteria in the pre-massage sample. There was no significant (p = 0.48) difference in the number of symptomatic UTI in men with a positive post-massage culture compared with those with a negative culture. No significant (p = 0.67) difference in the frequency distribution of positive versus negative post-massage cultures was detected between men with recurrent and sporadic UTI. Most SCI men are affected by asymptomatic bacterial prostatitis; however, bacterial prostatitis does not play a major role in the development of recurrent UTI. The indication for antibiotic treatment of chronic bacterial prostatitis in asymptomatic SCI men with recurrent UTI is questionable.

Intakes of meat, fish, poultry, and eggs and risk of prostate cancer progression.

PubMed

Richman, Erin L; Stampfer, Meir J; Paciorek, Alan; Broering, Jeanette M; Carroll, Peter R; Chan, June M

2010-03-01

Processed meat and fish have been shown to be associated with the risk of advanced prostate cancer, but few studies have examined diet after prostate cancer diagnosis and risk of its progression. We examined the association between postdiagnostic consumption of processed and unprocessed red meat, fish, poultry, and eggs and the risk of prostate cancer recurrence or progression. We conducted a prospective study in 1294 men with prostate cancer, without recurrence or progression as of 2004-2005, who were participating in the Cancer of the Prostate Strategic Urologic Research Endeavor and who were followed for an average of 2 y. We observed 127 events (prostate cancer death or metastases, elevated prostate-specific antigen concentration, or secondary treatment) during 2610 person-years. Intakes of processed and unprocessed red meat, fish, total poultry, and skinless poultry were not associated with prostate cancer recurrence or progression. Greater consumption of eggs and poultry with skin was associated with 2-fold increases in risk in a comparison of extreme quantiles: eggs [hazard ratio (HR): 2.02; 95% CI: 1.10, 3.72; P for trend = 0.05] and poultry with skin (HR: 2.26; 95% CI: 1.36, 3.76; P for trend = 0.003). An interaction was observed between prognostic risk at diagnosis and poultry. Men with high prognostic risk and a high poultry intake had a 4-fold increased risk of recurrence or progression compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003). Our results suggest that the postdiagnostic consumption of processed or unprocessed red meat, fish, or skinless poultry is not associated with prostate cancer recurrence or progression, whereas consumption of eggs and poultry with skin may increase the risk.

Intakes of meat, fish, poultry, and eggs and risk of prostate cancer progression1234

PubMed Central

Richman, Erin L; Stampfer, Meir J; Paciorek, Alan; Broering, Jeanette M; Carroll, Peter R; Chan, June M

2010-01-01

Background: Processed meat and fish have been shown to be associated with the risk of advanced prostate cancer, but few studies have examined diet after prostate cancer diagnosis and risk of its progression. Objective: We examined the association between postdiagnostic consumption of processed and unprocessed red meat, fish, poultry, and eggs and the risk of prostate cancer recurrence or progression. Design: We conducted a prospective study in 1294 men with prostate cancer, without recurrence or progression as of 2004–2005, who were participating in the Cancer of the Prostate Strategic Urologic Research Endeavor and who were followed for an average of 2 y. Results: We observed 127 events (prostate cancer death or metastases, elevated prostate-specific antigen concentration, or secondary treatment) during 2610 person-years. Intakes of processed and unprocessed red meat, fish, total poultry, and skinless poultry were not associated with prostate cancer recurrence or progression. Greater consumption of eggs and poultry with skin was associated with 2-fold increases in risk in a comparison of extreme quantiles: eggs [hazard ratio (HR): 2.02; 95% CI: 1.10, 3.72; P for trend = 0.05] and poultry with skin (HR: 2.26; 95% CI: 1.36, 3.76; P for trend = 0.003). An interaction was observed between prognostic risk at diagnosis and poultry. Men with high prognostic risk and a high poultry intake had a 4-fold increased risk of recurrence or progression compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003). Conclusions: Our results suggest that the postdiagnostic consumption of processed or unprocessed red meat, fish, or skinless poultry is not associated with prostate cancer recurrence or progression, whereas consumption of eggs and poultry with skin may increase the risk. PMID:20042525

Prospective Evaluation of Intraprostatic Inflammation and Focal Atrophy as a Predictor of Risk of High-Grade Prostate Cancer and Recurrence after Prostatectomy

DTIC Science & Technology

2016-09-01

the risk of cancer (e.g., gastritis-associated stomach cancer , colitis-associated gastric cancer , and hepatitis-associated liver cancer ), its effect...Grade Prostate Cancer and Recurrence after Prostatectomy PRINCIPAL INVESTIGATOR: Elizabeth A. Platz RECIPIENT: Johns Hopkins University Baltimore, MD...Intraprostatic Inflammation and Focal Atrophy as a Predictor of Risk of High-Grade Prostate Cancer and Recurrence after 5b. GRANT NUMBER PC110754

PSA-Stratified Performance of 18F- and 68Ga-PSMA PET in Patients with Biochemical Recurrence of Prostate Cancer.

PubMed

Dietlein, Felix; Kobe, Carsten; Neubauer, Stephan; Schmidt, Matthias; Stockter, Simone; Fischer, Thomas; Schomäcker, Klaus; Heidenreich, Axel; Zlatopolskiy, Boris D; Neumaier, Bernd; Drzezga, Alexander; Dietlein, Markus

2017-06-01

Several studies outlined the sensitivity of 68 Ga-labeled PET tracers against the prostate-specific membrane antigen (PSMA) for localization of relapsed prostate cancer in patients with renewed increase in the prostate-specific antigen (PSA), commonly referred to as biochemical recurrence. Labeling of PSMA tracers with 18 F offers numerous advantages, including improved image resolution, longer half-life, and increased production yields. The aim of this study was to assess the PSA-stratified performance of the 18 F-labeled PSMA tracer 18 F-DCFPyL and the 68 Ga-labeled reference 68 Ga-PSMA-HBED-CC. Methods: We examined 191 consecutive patients with biochemical recurrence according to standard acquisition protocols using 18 F-DCFPyL ( n = 62, 269.8 MBq, PET scan at 120 min after injection) or 68 Ga-PSMA-HBED-CC ( n = 129, 158.9 MBq, 60 min after injection). We determined PSA-stratified sensitivity rates for both tracers and corrected our calculations for Gleason scores using iterative matched-pair analyses. As an orthogonal validation, we directly compared tracer distribution patterns in a separate cohort of 25 patients, sequentially examined with both tracers. Results: After prostatectomy ( n = 106), the sensitivity of both tracers was significantly associated with absolute PSA levels ( P = 4.3 × 10 -3 ). Sensitivity increased abruptly, when PSA values exceeded 0.5 μg/L ( P = 2.4 × 10 -5 ). For a PSA less than 3.5 μg/L, most relapses were diagnosed at a still limited stage ( P = 3.4 × 10 -6 ). For a PSA of 0.5-3.5 μg/L, PSA-stratified sensitivity was 88% (15/17) for 18 F-DCFPyL and 66% (23/35) for 68 Ga-PSMA-HBED-CC. This significant difference was preserved in the Gleason-matched-pair analysis. Outside of this range, sensitivity was comparably low (PSA < 0.5 μg/L) or high (PSA > 3.5 μg/L). After radiotherapy ( n = 85), tracer sensitivity was largely PSA-independent. In the 25 patients examined with both tracers, distribution patterns of 18 F-DCFPyL and 68 Ga-PSMA-HBED-CC were strongly comparable ( P = 2.71 × 10 -8 ). However, in 36% of the PSMA-positive patients we detected additional lesions on the 18 F-DCFPyL scan ( P = 3.7 × 10 -2 ). Conclusion: Our data suggest that 18 F-DCFPyL is noninferior to 68 Ga-PSMA-HBED-CC, while offering the advantages of 18 F labeling. Our results indicate that imaging with 18 F-DCFPyL may even exhibit improved sensitivity in localizing relapsed tumors after prostatectomy for moderately increased PSA levels. Although the standard acquisition protocols, used for 18 F-DCFPyL and 68 Ga-PSMA-HBED-CC in this study, stipulate different activity doses and tracer uptake times after injection, our findings provide a promising rationale for validation of 18 F-DCFPyL in future prospective trials. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Diet and dietary supplement intervention trials for the prevention of prostate cancer recurrence: a review of the randomized controlled trial evidence.

PubMed

Van Patten, Cheri L; de Boer, Johan G; Tomlinson Guns, Emma S

2008-12-01

We review the effect of diet and dietary supplement interventions on prostate cancer progression, recurrence and survival. A literature search was conducted in MEDLINE, EMBASE and CINAHL to identify diet and dietary supplement intervention studies in men with prostate cancer using prostate specific antigen or prostate specific antigen doubling time as a surrogate serum biomarker of prostate cancer recurrence and/or survival. Of the 32 studies identified 9 (28%) were randomized controlled trials and the focus of this review. In these studies men had confirmed prostate cancer and elevated or increasing prostate specific antigen. Only 1 trial included men with metastatic disease. When body mass index was reported, men were overweight or obese. A significant decrease in prostate specific antigen was observed in some studies using a low fat vegan diet, soy beverage or lycopene supplement. While not often reported as an end point, a significant increase in prostate specific antigen doubling time was observed in a study on lycopene supplementation. In only 1 randomized controlled trial in men undergoing orchiectomy was a survival end point of fewer deaths with lycopene supplementation reported. A limited number of randomized controlled trials were identified in which diet and dietary supplement interventions appeared to slow disease progression in men with prostate cancer, although results vary. Studies were limited by reliance on the surrogate biomarker prostate specific antigen, sample size and study duration. Well designed trials are warranted to expand knowledge, replicate findings and further assess the impact of diet and dietary supplement interventions on recurrence and treatment associated morbidities.

Up-regulation of mismatch repair genes MSH6, PMS2 and MLH1 parallels development of genetic instability and is linked to tumor aggressiveness and early PSA recurrence in prostate cancer.

PubMed

Wilczak, Waldemar; Rashed, Semin; Hube-Magg, Claudia; Kluth, Martina; Simon, Ronald; Büscheck, Franziska; Clauditz, Till Sebastian; Grupp, Katharina; Minner, Sarah; Tsourlakis, Maria Christina; Möller-Koop, Christina; Graefen, Markus; Adam, Meike; Haese, Alexander; Wittmer, Corinna; Sauter, Guido; Izbicki, Jakob Robert; Huland, Hartwig; Schlomm, Thorsten; Steurer, Stefan; Krech, Till; Lebok, Patrick

2017-01-01

DNA mismatch repair (MMR) is integral to the maintenance of genetic stability. We aimed to evaluate the clinical impact of MMR gene expression in prostate cancer. The MMR genes MSH6, MLH1 and PMS2 were analyzed by immunohistochemistry on a tissue microarray containing 11152 prostate cancer specimens. Results were compared with ETS-related gene status and deletions of PTEN, 3p13, 5q21 and 6q15. MSH6, MLH1 and PMS2 expression was detectable in 89.5%, 85.4% and 85.0% of cancers and was particularly strong in cancers with advanced pathological tumor stage (P < 0.0001 each), high Gleason grade (P < 0.0001 each), nodal metastasis (P ≤ 0.0083) and early biochemical recurrence (P < 0.0001). High levels of MMR gene expression paralleled features of genetic instability, such as the number of genomic deletions per cancer; strong expression of all three MMR genes was found in 24%, 29%, 30%, 33% and 42% of cancers with no, one, two, three or four to five deletions (P < 0.0001). The prognostic value of the analyzed MMR genes was largely driven by the subset of cancers lacking ERG fusion (P < 0.0001), while the prognostic impact of MMR gene overexpression was only marginal in ERG-positive cancers. Multivariate analyses suggested an independent prognostic relevance of MMR genes in ERG-negative prostate cancers when compared with prognostic parameters available at the time of initial biopsy. In conclusion, MMR overexpression is common in prostate cancer and is linked to poor outcome as well as features indicating genetic instability. ERG fusion should be analyzed along with MMR gene expression in potential clinical tests. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Outcomes and toxicities in patients with intermediate-risk prostate cancer treated with brachytherapy alone or brachytherapy and supplemental external beam radiation therapy.

PubMed

Schlussel Markovic, Emily; Buckstein, Michael; Stone, Nelson N; Stock, Richard G

2018-05-01

To evaluate the cancer control outcomes and long-term treatment-related morbidity of brachytherapy as well as combination brachytherapy and external beam radiation therapy (EBRT) in patients with intermediate-risk prostate cancer. A retrospective review was conducted in a prospectively collected database of patients with intermediate-risk prostate cancer who were treated either with brachytherapy or brachytherapy and EBRT, with or without androgen deprivation therapy (ADT), in the period 1990-2014. Urinary and erectile dysfunction symptoms were measured using the International Prostate Symptom Score (IPSS), the Mount Sinai erectile function scale and the Sexual Health Inventory for Men (SHIM). Cancer control endpoints included biochemical failure and development of distant metastases. All statistical analyses were carried out using the Statistical Package for Social Science (SPSS). Survival curves were calculated using Kaplan-Meier actuarial methods and compared using log-rank tests. Cox regression multivariate analyses were used to test the effect of multiple variables on treatment outcomes. A total of 902 patients were identified, with a median follow-up of 91 months. Of these, 390 received brachytherapy and 512 received combination therapy with EBRT. In patients with one intermediate-risk factor, the addition of EBRT did not significantly affect freedom from biochemical failure or distant metastases. Among patients with two or three intermediate-risk factors, added EBRT did not improve freedom from biochemical failure. Significant differences in late toxicity between patients treated with brachytherapy vs combination brachytherapy and EBRT were identified including urge incontinence (P < 0.001), haematuria (P < 0.001), dysuria (P < 0.001), and change in quality-of-life IPSS (P = 0.002). These symptoms were reported by patients at any point during treatment follow-up. Analysis of patients who were potent before treatment using actuarial methods showed that patients receiving combination therapy more frequently experienced loss of potency, as measured by the Mount Sinai erectile function scale (P = 0.040). Brachytherapy monotherapy results in equal biochemical and distant control in both patients with one and more than one intermediate-risk features. While no significant benefit was shown, we believe that the addition of EBRT may prevent recurrence in patients with multiple intermediate-risk features and should be considered. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

Vaccine Therapy With or Without Sirolimus in Treating Patients With NY-ESO-1 Expressing Solid Tumors

ClinicalTrials.gov

2016-10-03

Anaplastic Astrocytoma; Anaplastic Oligoastrocytoma; Anaplastic Oligodendroglioma; Estrogen Receptor Negative; Estrogen Receptor Positive; Glioblastoma; Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma; Metastatic Renal Cell Cancer; Recurrent Adult Brain Neoplasm; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Colorectal Carcinoma; Recurrent Esophageal Carcinoma; Recurrent Gastric Carcinoma; Recurrent Hepatocellular Carcinoma; Recurrent Lung Carcinoma; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Uterine Corpus Carcinoma; Resectable Hepatocellular Carcinoma; Sarcoma; Stage IA Breast Cancer; Stage IA Ovarian Cancer; Stage IA Uterine Corpus Cancer; Stage IB Breast Cancer; Stage IB Ovarian Cancer; Stage IB Uterine Corpus Cancer; Stage IC Ovarian Cancer; Stage II Uterine Corpus Cancer; Stage IIA Breast Cancer; Stage IIA Lung Carcinoma; Stage IIA Ovarian Cancer; Stage IIB Breast Cancer; Stage IIB Esophageal Cancer; Stage IIB Lung Carcinoma; Stage IIB Ovarian Cancer; Stage IIB Skin Melanoma; Stage IIC Ovarian Cancer; Stage IIC Skin Melanoma; Stage IIIA Breast Cancer; Stage IIIA Esophageal Cancer; Stage IIIA Lung Carcinoma; Stage IIIA Ovarian Cancer; Stage IIIA Skin Melanoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Breast Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Skin Melanoma; Stage IIIB Uterine Corpus Cancer; Stage IIIC Breast Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Skin Melanoma; Stage IIIC Uterine Corpus Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Esophageal Cancer; Stage IV Ovarian Cancer; Stage IV Prostate Cancer; Stage IV Skin Melanoma; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

PSMA, EpCAM, VEGF and GRPR as imaging targets in locally recurrent prostate cancer after radiotherapy.

PubMed

Rybalov, Maxim; Ananias, Hildo J K; Hoving, Hilde D; van der Poel, Henk G; Rosati, Stefano; de Jong, Igle J

2014-04-10

In this retrospective pilot study, the expression of the prostate-specific membrane antigen (PSMA), the epithelial cell adhesion molecule (EpCAM), the vascular endothelial growth factor (VEGF) and the gastrin-releasing peptide receptor (GRPR) in locally recurrent prostate cancer after brachytherapy or external beam radiotherapy (EBRT) was investigated, and their adequacy for targeted imaging was analyzed. Prostate cancer specimens were collected of 17 patients who underwent salvage prostatectomy because of locally recurrent prostate cancer after brachytherapy or EBRT. Immunohistochemistry was performed. A pathologist scored the immunoreactivity in prostate cancer and stroma. Staining for PSMA was seen in 100% (17/17), EpCAM in 82.3% (14/17), VEGF in 82.3% (14/17) and GRPR in 100% (17/17) of prostate cancer specimens. Staining for PSMA, EpCAM and VEGF was seen in 0% (0/17) and for GRPR in 100% (17/17) of the specimens' stromal compartments. In 11.8% (2/17) of cases, the GRPR staining intensity of prostate cancer was higher than stroma, while in 88.2% (15/17), the staining was equal. Based on the absence of stromal staining, PSMA, EpCAM and VEGF show high tumor distinctiveness. Therefore, PSMA, EpCAM and VEGF can be used as targets for the bioimaging of recurrent prostate cancer after EBRT to exclude metastatic disease and/or to plan local salvage therapy.

Patient-Level DNA Damage and Repair Pathway Profiles and Prognosis After Prostatectomy for High-Risk Prostate Cancer

PubMed Central

Evans, Joseph R.; Zhao, Shuang G.; Chang, S. Laura; Tomlins, Scott A.; Erho, Nicholas; Sboner, Andrea; Schiewer, Matthew J.; Spratt, Daniel E.; Kothari, Vishal; Klein, Eric A.; Den, Robert B.; Dicker, Adam P.; Karnes, R. Jeffrey; Yu, Xiaochun; Nguyen, Paul L.; Rubin, Mark A.; de Bono, Johann; Knudsen, Karen E.; Davicioni, Elai; Feng, Felix Y.

2017-01-01

IMPORTANCE A substantial number of patients diagnosed with high-risk prostate cancer are at risk for metastatic progression after primary treatment. Better biomarkers are needed to identify patients at the highest risk to guide therapy intensification. OBJECTIVE To create a DNA damage and repair (DDR) pathway profiling method for use as a prognostic signature biomarker in high-risk prostate cancer. DESIGN, SETTING, AND PARTICIPANTS A cohort of 1090 patients with high-risk prostate cancer who underwent prostatectomy and were treated at 3 different academic institutions were divided into a training cohort (n = 545) and 3 pooled validation cohorts (n = 232, 130, and 183) assembled for case-control or case-cohort studies. Profiling of 9 DDR pathways using 17 gene sets for GSEA (Gene Set Enrichment Analysis) of high-density microarray gene expression data from formalin-fixed paraffin-embedded prostatectomy samples with median 10.3 years follow-up was performed. Prognostic signature development from DDR pathway profiles was studied, and DDR pathway gene mutation in published cohorts was analyzed. MAIN OUTCOMES AND MEASURES Biochemical recurrence-free, metastasis-free, and overall survival. RESULTS Across the training cohort and pooled validation cohorts, 1090 men were studied; mean (SD) age at diagnosis was 65.3 (6.4) years. We found that there are distinct clusters of DDR pathways within the cohort, and DDR pathway enrichment is only weakly correlated with clinical variables such as age (Spearman ρ [ρ], range, −0.07 to 0.24), Gleason score (ρ, range, 0.03 to 0.20), prostate-specific antigen level (ρ, range, −0.07 to 0.10), while 13 of 17 DDR gene sets are strongly correlated with androgen receptor pathway enrichment (ρ, range, 0.33 to 0.82). In published cohorts, DDR pathway genes are rarely mutated. A DDR pathway profile prognostic signature built in the training cohort was significantly associated with biochemical recurrence-free, metastasis-free, and overall survival in the pooled validation cohorts independent of standard clinicopathological variables. The prognostic performance of the signature for metastasis-free survival appears to be stronger in the younger patients (HR, 1.67; 95%CI, 1.12–2.50) than in the older patients (HR, 0.77; 95%CI, 0.29–2.07) on multivariate Cox analysis. CONCLUSIONS AND RELEVANCE DNA damage and repair pathway profiling revealed patient-level variations and the DDR pathways are rarely affected by mutation. A DDR pathway signature showed strong prognostic performance with the long-term outcomes of metastasis-free and overall survival that may be useful for risk stratification of high-risk prostate cancer patients. PMID:26746117

Long-Term Outcomes of Using Hyaluronic Acid-Carboxymethylcellulose Adhesion Barrier Film on the Neurovascular Bundle.

PubMed

Patel, Rutveej; Modi, Parth K; Elsamra, Sammy E; Kim, Isaac Yi

2016-06-01

We hypothesize that the use of hyaluronic acid-carboxymethylcellulose (HACM) adhesion barrier at the neurovascular bundle may hasten the return of erectile function after robot-assisted laparoscopic prostatectomy. A retrospective review identified 462 consecutive patients who underwent a nerve-sparing prostatectomy between 2009 and 2012. The first 246 patients were administered the barrier film, while the next 216 patients, the control group, did not receive HACM. Postoperative erectile function and oncologic outcomes were compared. Independent t-test and Kaplan-Meier analysis were conducted, p < 0.05 was considered significant. The two groups were well matched, without significant differences in age, weight, operative time, prostate size, preoperative prostate-specific antigen, sexual health inventory for men (SHIM), or AUA symptom scores. The mean SHIM was significantly higher for the experimental group at 6 months (6.39 vs 4.75, p = 0.008), 9 months (7.32 vs 5.44, p = 0.006), 1 year (8.52 vs 6.90, p = 0.049), and 18 months (10.01 vs 7.60, p = 0.018). This effect was not noted beyond 18 months. A subgroup analysis of patients with initial SHIM scores 22 or greater demonstrated a higher rate of return to the preoperative SHIM score for the barrier film group, 23% vs 12% (p = 0.046). There was no significant difference in biochemical recurrence between groups, with a median follow-up duration of 18 months. HACM application at the neurovascular bundle during prostatectomy may decrease the time to return of erectile function, with improved SHIM at 6 to 18 months after surgery. This effect is more pronounced in patients with better baseline erectile function. There is no significant effect on biochemical recurrence.

Novel multi-peptide vaccination in Hla-A2+ hormone sensitive patients with biochemical relapse of prostate cancer.

PubMed

Feyerabend, Susan; Stevanovic, Stefan; Gouttefangeas, Cécile; Wernet, Dorothee; Hennenlotter, Jörg; Bedke, Jens; Dietz, Klaus; Pascolo, Steve; Kuczyk, Markus; Rammensee, Hans-Georg; Stenzl, Arnulf

2009-06-15

A phase I/II trial was conducted to assess feasibility and tolerability of tumor associated antigen peptide vaccination in hormone sensitive prostate carcinoma (PC) patients with biochemical recurrence after primary surgical treatment. Nineteen HLA-A2 positive patients with rising PSA without detectable metastatic disease or local recurrence received 11 HLA-A*0201-restricted and two HLA class II synthetic peptides derived from PC tumor antigens subcutaneously for 18 months or until PSA progression. The vaccine was emulgated in montanide ISA51 and combined with imiquimod, GM-CSF, mucin-1-mRNA/protamine complex, local hyperthermia or no adjuvant. PSA was assessed, geometric mean doubling times (DT) calculated and clinical performance monitored. PSA DT of 4 out of 19 patients (21%) increased from 4.9 to 25.8 months during vaccination. Out of these, two patients (11%) exhibited PSA stability for 28 and 31 months which were still continuing at data cut-off. One patient showed no change of PSA DT during vaccination but decline after the therapy. Three patients had an interim PSA decline or DT increase followed by DT decrease compared to baseline PSA DT. Three of the responding patients received imiquimod and one the mucin-1-mRNA/protamine complex as adjuvant; both are Toll-like receptor-7 agonists. Eleven (58%) patients had progressive PSA values. The vaccine was well tolerated, and no grade III or IV toxicity occurred. Multi-peptide vaccination stabilized or slowed down PSA progress in four of 19 cases. The vaccination approach is promising with moderate adverse events. Long-term stability delayed androgen deprivation up to 31 months. TLR-7 co-activation seems to be beneficial.

Clinicopathological characteristics of incidental prostate cancer discovered from radical cystoprostatectomy specimen: a multicenter French study.

PubMed

Pignot, Géraldine; Salomon, Laurent; Neuzillet, Yann; Masson-Lecomte, Alexandra; Lebacle, Cédric; Patard, Jean-Jacques; Lunardi, Pierre; Rischmann, Pascal; Pasticier, Gilles; Bernhard, Jean-Christophe; Cohen, Jérémy; Timsit, Marc-Olivier; Verkarre, Virginie; Peyronnet, Benoit; Verhoest, Gregory; Le Goux, Constance; Zerbib, Marc; Brecheteau, François; Bigot, Pierre; Larre, Stéphane; Murez, Thibault; Thuret, Rodolphe; Lacarriere, Emeric; Champy, Cécile; Roupret, Morgan; Comperat, Eva; Berger, Julien; Descazeaud, Aurélien; Toledano, Harry; Bastide, Cyrille; Lavilledieu, Sébastien; Avances, Christophe; Delage, Francky; Valeri, Antoine; Molimard, Benoit; Houlgatte, Alain; Gres, Pascal; Donnaint, Alain; Kleinclauss, François; Legal, Sophie; Doerfler, Arnaud; Koutlidis, Nicolas; Cormier, Luc; Hetet, Jean-François; Colls, Philippe; Arvin-Berod, Alexis; Rambeaud, Jean-Jacques; Quintens, Hervé; Soulie, Michel; Pfister, Christian

2014-02-01

The present study assessed the incidence and histopathological features of incidentally diagnosed prostate cancer (PCa) in specimens from radical cystoprostatectomy (RCP) for bladder cancer. The patient outcomes also were evaluated. We retrospectively reviewed the histopathological features and survival data of 4,299 male patients who underwent a RCP for bladder cancer at 25 French centers between January 1996 and June 2012. No patients had preoperative clinical or biological suspicion of PCa. Among the 4,299 RCP specimens, PCa was diagnosed in 931 patients (21.7%). Most tumors (90.1%) were organ-confined (pT2), whereas 9.9% of them were diagnosed at a locally advanced stage (≥pT3). Gleason score was <6 in 129 cases (13.9%), 6 in 575 cases (61.7%), 7 (3 + 4) in 149 cases (16.0%), 7 (4 + 3) in 38 cases (4.1%), and >7 in 40 cases (4.3%). After a median follow-up of 25.5 months (interquartile range 14.2-47.4), 35.4% of patients had bladder cancer recurrence and 23.8% died of bladder cancer. Only 16 patients (1.9%) experienced PCa biochemical recurrence during follow-up, and no preoperative predictive factor was identified. No patients died from PCa. The rate of incidentally diagnosed PCa in RCP specimens was 21.7%. The majority of these PCas were organ-confined. PCa recurrence occurred in only 1.9% of cases during follow-up.

Prostate-specific membrane antigen for prostate cancer theranostics: from imaging to targeted therapy.

PubMed

Arsenault, Frédéric; Beauregard, Jean-Mathieu; Pouliot, Frédéric

2018-06-22

In recent years, major advances in molecular imaging of prostate cancers (PCa) were made with the development and clinical validation of highly accurate PET tracers to stage and restage the disease. Prostate-specific membrane antigen (PSMA) is a transmembrane protein highly expressed in PCa, and its expression has led to the development of PSMA-binding radiopharmaceuticals for molecular imaging or radioligand therapy (RLT). We herein review the recent literature published on diagnostic and therapeutic (i.e. theranostic) PSMA tracers. Development in small PSMA-targeted molecules labeled with gallium-68 and fluorine-18 show promising results for primary staging and detection of disease at biochemical recurrence using PET/computed tomography (PET/CT). Studies show a higher sensitivity and specificity, along with an improved detection rate over conventional imaging (CT scan and bone scan) or choline PET tracers, especially for restaging after prostate-specific antigen failure following loco-regional therapy. In addition, some PSMA tracers can be labeled with beta-minus and alpha particle emitters, yielding encouraging response rates and low toxicity, and potentially offering a new line of targeted therapy for metastatic castration-resistant PCa. PSMA-targeted tracers have shown unprecedented accuracy to stage and restage PCa using PET/CT. Given their specific biodistribution toward PCa tissue, PSMA RLT now offers new therapeutic possibilities to target metastatic PCa. Prospective multicenter randomized studies investigating the clinical impact management impacts of PSMA-targeted molecules are urgently needed.

68Ga-PSMA-11 PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy and PSA <0.5 ng/ml. Efficacy and impact on treatment strategy.

PubMed

Farolfi, Andrea; Ceci, Francesco; Castellucci, Paolo; Graziani, Tiziano; Siepe, Giambattista; Lambertini, Alessandro; Schiavina, Riccardo; Lodi, Filippo; Morganti, Alessio G; Fanti, Stefano

2018-06-15

The primary aim of this retrospective, single-centre analysis was to assess the performance of 68 Ga-PSMA-11 PET/CT in prostate cancer (PCa) patients in early PSA failure after radical prostatectomy (RP). The secondary aim was to assess the potential impact of 68 Ga-PSMA-11 PET/CT on treatment strategy. 68 Ga-PSMA-11 PET/CT is performed in our institution within an investigational new drug (IND) trial in PCa patients with biochemical recurrence (BCR). The records of all patients enrolled between March 2016 and July 2017 were evaluated. These records were retrospectively analysed according to the following inclusion criteria: (a) RP as primary therapy, (b) proven BCR, ©) PSA levels in the range 0.2-0.5 ng/ml at the time of the 68 Ga-PSMA-11 PET/CT investigation, and (d) no salvage radiotherapy (S-RT) performed after recurrence. The performance of 68 Ga-PSMA-11 PET/CT was evaluated in terms of detection rate on a per-patient and a per-region basis (local vs. distant lesions). We further performed an intention-to-treat (ITT) analysis. The patient cohort was grouped into three subpopulations, blinded to the 68 Ga-PSMA-11 PET/CT results, according to the patients' characteristics and different patterns of treatment: (1) S-RT (with or without systemic treatment), (2) stereotactic body radiotherapy (SBRT) (with or without systemic treatment), and (3) systemic treatment. The treatment strategy was re-evaluated for each patient taking into consideration the 68 Ga-PSMA-11 PET/CT images. We enrolled 119 PCa patients (mean age 66 years, range 44-78 years) with a mean PSA level at the time of 68 Ga-PSMA-11 PET/CT of 0.34 ng/ml (median 0.32 ng/ml, SD ±0.09, range 0.20-0.50 ng/ml). 68 Ga-PSMA-1 1 PET/CT was positive in 41 of the 119 patients, resulting in an overall detection rate of 34.4%. 68 Ga-PSMA-11 uptake was observed in the prostate bed (3 patients, 2.5%), in the pelvic lymph nodes (21, 17.6%), in the retroperitoneal lymph nodes (4, 3.4%) and in the skeleton (21, 17.6%). Regarding ITT, 81 patients (68.1%) were considered possible candidates for S-RT only in the prostate bed and none of the patients (0%) for SBRT. According to the 68 Ga-PSMA-11 PET/CT results, the intended treatment was changed in 36 patients (30.2%). According to the PET/CT results, S-RT was recommended in 70 patients (58.8%), only to the prostate bed in 58 (48.7%) and SBRT in 29 (24.4%). The intended RT planning was modified in 36 (87.8%) of 41 patients with a positive 68 Ga-PSMA-11 PET/CT result. In our patient series with PSA levels <0.5 ng/ml, 68 Ga-PSMA-11 PET/CT had a detection rate of 34.4%. In the ITT analysis, 30.2% of patients had a change in the intended treatment. These data support the hypothesis that 68 Ga-PSMA-11 PET/CT is a useful procedure in the management of PCa patients showing early recurrence after RP, and should be implemented in routine clinical practice.

Is Eotaxin-1 a serum and urinary biomarker for prostate cancer detection and recurrence?

PubMed

Heidegger, Isabel; Höfer, Julia; Luger, Markus; Pichler, Renate; Klocker, Helmut; Horninger, Wolfgang; Steiner, Eberhard; Jochberger, Stefan; Culig, Zoran

2015-12-01

Eotaxin-1 (CCL11) is a protein expressed in various tissues influencing immunoregulatory processes by acting as selective eosinophil chemo-attractant. In prostate cancer (PCa), the expression and functional role of CCL11 have not been intensively investigated so far. Therefore, the aim of the present study was to investigate the diagnostic or prognostic potential of Eotaxin-1 in PCa patients. We analyzed serum from 140 patients who have undergone prostate biopsy due to elevated prostate-specific antigen (PSA) levels as well as serum of 20 individuals with PSA levels < 1ng/ml (healthy control group). Moreover, 40 urine samples were analyzed. A custom-made Q-Plex array ELISA (Quansys Biosciences) for the detection of Eotaxin-1 was performed and Q-View Software used for quantification. In addition, clinical courses of patients documented in our Prostate Biobank database were analyzed. ROC and survival analyses were used to determine the diagnostic and prognostic power of Eotaxin-1 levels. Serum Eotaxin-1 levels were significantly decreased in PCa (P = 0.006) as well as in benign prostate hyperplasia (P = 0.0006) compared to the control group. ROC analysis revealed that Eotaxin-1 is a significant marker to distinguish PCa from disease-free prostate. Moreover, we found that Eotaxin-1 expression is significantly decreased in Gleason score (GS) 6 (P = 0.0135) and GS 8 (P = 0.0057) patients compared to samples of healthy men, respectively. However, PCa aggressiveness was not predictable by Eotaxin-1 levels. In line with serum analyses, urine Eotaxin-1 was significantly decreased in patients with PCa compared to cancer-free individuals (P = 0.0185) but was not different between cancers of different GS. Patientś follow-up analyses showed no significant correlation between serum Eotaxin-1 levels and time to biochemical recurrence. Survival analyses also revealed no significant changes in progression-free survival among low (≤ 112.2 pg/ml) and high (> 112.2 pg/ml) Eotaxin-1 serum levels. Although this study has not established a prognostic role of Eotaxin-1 in PCa patients, this chemokine may serve as a diagnostic marker to distinguish between disease-free prostate and cancer. © 2015 Wiley Periodicals, Inc.

Prostate Specific Antigen (PSA) as Predicting Marker for Clinical Outcome and Evaluation of Early Toxicity Rate after High-Dose Rate Brachytherapy (HDR-BT) in Combination with Additional External Beam Radiation Therapy (EBRT) for High Risk Prostate Cancer.

PubMed

Ecke, Thorsten H; Huang-Tiel, Hui-Juan; Golka, Klaus; Selinski, Silvia; Geis, Berit Christine; Koswig, Stephan; Bathe, Katrin; Hallmann, Steffen; Gerullis, Holger

2016-11-10

High-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT) is a common treatment option for locally advanced prostate cancer (PCa). Seventy-nine male patients (median age 71 years, range 50 to 79) with high-risk PCa underwent HDR-BT following EBRT between December 2009 and January 2016 with a median follow-up of 21 months. HDR-BT was administered in two treatment sessions (one week interval) with 9 Gy per fraction using a planning system and the Ir192 treatment unit GammaMed Plus iX. EBRT was performed with CT-based 3D-conformal treatment planning with a total dose administration of 50.4 Gy with 1.8 Gy per fraction and five fractions per week. Follow-up for all patients was organized one, three, and five years after radiation therapy to evaluate early and late toxicity side effects, metastases, local recurrence, and prostate-specific antigen (PSA) value measured in ng/mL. The evaluated data included age, PSA at time of diagnosis, PSA density, BMI (body mass index), Gleason score, D'Amico risk classification for PCa, digital rectal examination (DRE), PSA value after one/three/five year(s) follow-up (FU), time of follow-up, TNM classification, prostate volume, and early toxicity rates. Early toxicity rates were 8.86% for gastrointestinal, and 6.33% for genitourinary side effects. Of all treated patients, 84.81% had no side effects. All reported complications in early toxicity were grade 1. PSA density at time of diagnosis ( p = 0.009), PSA on date of first HDR-BT ( p = 0.033), and PSA on date of first follow-up after one year ( p = 0.025) have statistical significance on a higher risk to get a local recurrence during follow-up. HDR-BT in combination with additional EBRT in the presented design for high-risk PCa results in high biochemical control rates with minimal side-effects. PSA is a negative predictive biomarker for local recurrence during follow-up. A longer follow-up is needed to assess long-term outcome and toxicities.

Management of high risk metastatic prostate cancer: the case for novel therapies.

PubMed

Brand, Timothy C; Tolcher, Anthony W

2006-12-01

We reviewed the results of preliminary studies of select novel agents for metastatic prostate cancer and discuss the potential benefit of these agents for earlier stage disease, eg biochemically recurrent prostate cancer with high risk features. Available data on select investigational immunotherapies as well as endothelin-A receptor antagonists and survivin inhibitors were obtained and reviewed through PubMed searches, conference proceedings and unpublished proprietary information, when available. A large number of promising agents are in varying stages of development. Phase III results have been reported for the endothelin-A receptor antagonist atrasentan. Several immunotherapies are currently in phase II/III trials, namely the GM-CSF transduced tumor cell vaccine GVAX, the prostatic acid phosphatase loaded dendritic cell vaccine Provenge and the prostate specific antigen expressing poxvirus vaccine PROSTVAC-VF. Another immunotherapy, the prostate specific membrane antigen immunoconjugate MLN2704 (Millennium Pharmaceuticals, Cambridge, Massachusetts), is in phase I/II study. The first clinical inhibitors of survivin are in early phase I studies. Several of these agents, including atrasentan, have shown statistically significant but modest effects in the advanced disease setting in which they have been studied. Clinical trial design with these novel therapies presents particular challenges since most of these agents may induce disease stabilization rather than disease regression. There is a risk of false-negative results and failure to recognize a potentially efficacious agent if these cytostatic agents are studied only in men with advanced, heavily pretreated disease in whom life expectancy is measured in months. We advocate the early referral and enrollment of men with high risk prostate cancer in clinical trials.

Proton Therapy as Salvage Treatment for Local Relapse of Prostate Cancer Following Cryosurgery or High-Intensity Focused Ultrasound

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holtzman, Adam L.; Hoppe, Bradford S., E-mail: bhoppe@floridaproton.org; Letter, Haley P.

Purpose: Local recurrence of prostate cancer after cryosurgery (CS) and high-intensity focused ultrasound (HIFU) is an emerging problem for which optimal management is unknown. Proton therapy (PT) may offer advantages over other local therapeutic options. This article reviews a single institution's experience using PT for salvage of local recurrent disease after HIFU or CS. Methods and Materials: We reviewed the medical records of 21 consecutive patients treated with salvage PT following a local recurrence of prostate cancer after CS (n=12) or HIFU (n=9) between January 2007 and July 2014. Patients were treated to a median dose of 74 Gy(relative biological effectivenessmore » [RBE]; range: 74-82 Gy[RBE]) and 8 patients received androgen deprivation therapy with radiation therapy. Patients were evaluated for quality of life (QOL) by using the Expanded Prostate Index Composite questionnaire and toxicity by using Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment, every 6 months for 2 years after treatment, and then annually. Results: Median follow-up was 37 months (range: 6-95 months). The 3-year biochemical progression-free survival (bPFS) rate was 77%. The 3-year grade 3 toxicity rate was 17%; however, 2 of these patients had pre-existing grade 3 GU toxicities from their HIFU/CRYO prior to PT. At 1 year, bowel summary, urinary incontinence, and urinary obstructive QOL scores declined, but only the bowel QOL score at 12 months met the minimally important difference threshold. Conclusions: PT achieved a high rate of bPFS with acceptable toxicity and minimal changes in QOL scores compared with baseline pre-PT functions. Although most patients have done fairly well, the study size is small, follow-up is short, and early results suggest that outcomes with PT for salvage after HIFU or CS failure are inferior to outcomes with PT given in the de novo setting with respect to disease control, toxicity, and QOL.« less

Genetic and Molecular Mechanisms in Assessing Response in Patients With Prostate Cancer Receiving Enzalutamide Therapy

ClinicalTrials.gov

2018-01-22

Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma in the Soft Tissue; Metastatic Prostatic Adenocarcinoma; Prostate Carcinoma Metastatic in the Bone; PSA Progression; Recurrent Prostate Carcinoma; Stage III Prostate Adenocarcinoma; Stage IV Prostate Adenocarcinoma

Oncologic Outcomes After Robot-assisted Radical Prostatectomy: A Large European Single-centre Cohort with Median 10-Year Follow-up.

PubMed

Rajan, Prabhakar; Hagman, Anna; Sooriakumaran, Prasanna; Nyberg, Tommy; Wallerstedt, Anna; Adding, Christofer; Akre, Olof; Carlsson, Stefan; Hosseini, Abolfazl; Olsson, Mats; Egevad, Lars; Wiklund, Fredrik; Steineck, Gunnar; Wiklund, N Peter

2016-11-02

Robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa) treatment has been widely adopted with limited evidence for long-term (>5 yr) oncologic efficacy. To evaluate long-term oncologic outcomes following RARP. Prospective cohort study of 885 patients who underwent RARP as monotherapy for PCa between 2002 and 2006 in a single European centre and followed up until 2016. RARP as monotherapy. Biochemical recurrence (BCR)-free survival (BCRFS), salvage therapy (ST)-free survival (STFS), prostate cancer-specific survival (CSS), and overall survival (OS) were estimated using the Kaplan-Meier method, and event-time distributions were compared using the log-rank test. Variables predictive of BCR and ST were identified using Cox proportional hazards models. We identified 167 BCRs, 110 STs, 16 PCa-related deaths, and 51 deaths from other/unknown causes. BCRFS, STFS, CSS, and OS rates were 81.8%, 87.5%, 98.5%, and 93.0%, respectively, at median follow-up of 10.5 yr. On multivariable analysis, the strongest independent predictors of both BCR and ST were preoperative Gleason score, pathological T stage, positive surgical margins (PSMs), and preoperative prostate-specific antigen. PSM >3mm/multifocal but not ≤3mm independently affected the risk of both BCR and ST. Study limitations include a lack of centralised histopathologic reporting, lymph node and post-operative tumour volume data in a historical cohort, and patient-reported outcomes. RARP appears to confer effective long-term oncologic efficacy. The risk of BCR or ST is unaffected by ≤3mm PSM, but further follow-up is required to determine any impact on CSS. Robot-assisted surgery for prostate cancer is effective 10 yr after treatment. Very small (<3mm) amounts of cancer at the cut edge of the prostate do not appear to impact on recurrence risk and the need for additional treatment, but it is not yet known whether this affects the risk of death from prostate cancer. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

68Ga-PSMA PET/CT in patients with recurrent prostate cancer after radical treatment: prospective results in 314 patients.

PubMed

Caroli, Paola; Sandler, Israel; Matteucci, Federica; De Giorgi, Ugo; Uccelli, Licia; Celli, Monica; Foca, Flavia; Barone, Domenico; Romeo, Antonino; Sarnelli, Anna; Paganelli, Giovanni

2018-06-19

We studied the usefulness of 68 Ga-prostate-specific membrane antigen (PSMA) PET/CT for detecting relapse in a prospective series of patients with biochemical recurrence (BCR) of prostate cancer (PCa) after radical treatment. Patients with BCR of PCa after radical surgery and/or radiotherapy with or without androgen-deprivation therapy were included in the study. 68 Ga-PSMA PET/CT scans performed from the top of the head to the mid-thigh 60 min after intravenous injection of 150 ± 50 MBq of 68 Ga-PSMA were interpreted by two nuclear medicine physicians. The results were correlated with prostate-specific antigen (PSA) levels at the time of the scan (PSApet), PSA doubling time, Gleason score, tumour stage, postsurgery tumour residue, time from primary therapy to BCR, and patient age. When available, 68 Ga-PSMA PET/CT scans were compared with negative 18 F-choline PET/CT scans routinely performed up to 1 month previously. From November 2015 to October 2017, 314 PCa patients with BCR were evaluated. Their median age was 70 years (range 44-92 years) and their median PSApet was 0.83 ng/ml (range 0.003-80.0 ng/ml). 68 Ga-PSMA PET/CT was positive (one or more suspected PCa lesions detected) in 197 patients (62.7%). Lesions limited to the pelvis, i.e. the prostate/prostate bed and/or pelvic lymph nodes (LNs), were detected in 117 patients (59.4%). At least one distant lesion (LNs, bone, other organs, separately or combined with local lesions) was detected in 80 patients (40.6%). PSApet was higher in PET-positive than in PET-negative patients (P < 0.0001). Of 88 patients negative on choline PET/CT scans, 59 (67%) were positive on 68 Ga-PSMA PET/CT. We confirmed the value of 68 Ga-PSMA PET/CT in restaging PCa patients with BCR, highlighting its superior performance and safety compared with choline PET/CT. Higher PSApet was associated with a higher relapse detection rate.

[Salvage cryotherapy of prostate cancer after failed external radiotherapy and brachytherapy: Morbidity and mid-term oncological results].

PubMed

Gevorgyan, A; Hétet, J-F; Robert, M; Duchattelle-Dussaule, V; Corno, L; Boulay, I; Baumert, H

2018-04-01

To study the oncologic and functional results of salvage cryotherapy after failure of external radiotherapy and brachytherapy. Patients treated by total salvage cryotherapy (3rd generation) in 2 centers (Groupe Hospitalier Saint-Joseph in Paris and Clinique Jule-Verne Nantes) in between January 2008 and April 2016 were included. The biochemical recurrence-free survival (BRFS) was calculated using the Phoenix criteria (PSA>nadir+2ng/mL). The functional results were assessed clinically. Ninety-seven patients with an average follow up of 39.4months were evaluated retrospectively. The 5-year biochemical recurrence-free survival (5y-BRFS) among all patients was 58.1% (IC à 95% [45.9-68.5]). Low and intermediate risk patients (d'Amico classification) were less prone to biochemical recurrence than high risk (81.05% (IC à 95% [64.1-90.5]) 5y-BRFS as opposed to 35.09% (IC à 95% [20.1-50.4]) respectively) (P<0.0001). As were patients with a Gleason score≤7 75.35% (IC à 95% [59.7-85.6]) compared to 32.31% (IC à 95% [16.5-49.2]) for higher Gleason (>7 scores [P=0.0002]). A Gleason score>7 (OR=6.9; P=0.002), PSA nadir>1ng/mL (OR=25.8; P=0.0026) and peri-urethral invasion (OR=35.8; P<0.001) were major risk factors for local recurrence in univariate analysis. In multivariate analysis, only PSA nadir>1ng/mL (OR=12.9; P=0.042) and peri-urethral invasion (OR=21.6; P=0.0003) remain major risk factors for recurrence. About 13 (16.46%) patients were incontinent of which 3 (3.79%) required placement of an artificial urinary sphincter. Erectile dysfunction was present in 66 (83.5%) patients. Recto-urethral fistula was uncommon in 1 patient (1.27%). Salvage cryotherapy after failure of external radiotherapy and brachytherapy is a reliable and reproducible technique with promising oncological and functional results. Study of prognostic factors will help better select eligible patients in the future. 4. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Magnetic resonance spectroscopy-guided transperineal prostate biopsy and brachytherapy for recurrent prostate cancer.

PubMed

Barnes, Agnieszka Szot; Haker, Steven J; Mulkern, Robert V; So, Minna; D'Amico, Anthony V; Tempany, Clare M

2005-12-01

Brachytherapy targeted to the peripheral zone with magnetic resonance imaging (MRI) guidance is a prostate cancer treatment option with potentially fewer complications than other treatments. Follow-up MRI when failure is suspected is, however, difficult because of radiation-induced changes. Furthermore, MR spectroscopy (MRS) is compromised by susceptibility artifacts from radioactive seeds in the peripheral zone. We report a case in which combined MRI/MRS was useful for the detection of prostate cancer in the transitional zone in patients previously treated with MR-guided brachytherapy. We propose that MRI/MRS can help detect recurrent prostate cancer, guide prostate biopsy, and help manage salvage treatment decisions.

Sentinel Lymph Node Dissection to Select Clinically Node-negative Prostate Cancer Patients for Pelvic Radiation Therapy: Effect on Biochemical Recurrence and Systemic Progression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grivas, Nikolaos, E-mail: n.grivas@nki.nl; Wit, Esther; Pos, Floris

Purpose: To assess the efficacy of robotic-assisted laparoscopic sentinel lymph node (SLN) dissection (SLND) to select those patients with prostate cancer (PCa) who would benefit from additional pelvic external beam radiation therapy and long-term androgen deprivation therapy (ADT). Methods and Materials: Radioisotope-guided SLND was performed in 224 clinically node-negative patients scheduled to undergo external beam radiation therapy. Patients with histologically positive SLNs (pN1) were also offered radiation therapy to the pelvic lymph nodes, combined with 3 years of ADT. Biochemical recurrence (BCR), overall survival, and metastasis-free (including pelvic and nonregional lymph nodes) survival (MFS) rates were retrospectively calculated. The Briganti andmore » Kattan nomogram predictions were compared with the observed pN status and BCR. Results: The median prostate-specific antigen (PSA) value was 15.4 ng/mL (interquartile range [IQR] 8-29). A total number of 834 SLNs (median 3 per patient; IQR 2-5) were removed. Nodal metastases were diagnosed in 42% of the patients, with 150 SLNs affected (median 1; IQR 1-2). The 5-year BCR-free and MFS rates for pN0 patients were 67.9% and 87.8%, respectively. The corresponding values for pN1 patients were 43% and 66.6%. The PSA level and number of removed SLNs were independent predictors of BCR and MFS, and pN status was an additional independent predictor of BCR. The 5-year overall survival rate was 97.6% and correlated only with pN status. The predictive accuracy of the Briganti nomogram was 0.665. Patients in the higher quartiles of Kattan nomogram prediction of BCR had better than expected outcomes. The complication rate from SLND was 8.9%. Conclusions: For radioisotope-guided SLND, the high staging accuracy is accompanied by low morbidity. The better than expected outcomes observed in the lower quartiles of BCR prediction suggest a role for SLN biopsy as a potential selection tool for the addition of pelvic radiation therapy and ADT intensification in pN1 patients.« less

A phase I study of muscadine grape skin extract in men with biochemically recurrent prostate cancer: Safety, tolerability, and dose determination.

PubMed

Paller, Channing J; Rudek, Michelle A; Zhou, Xian C; Wagner, William D; Hudson, Tamaro S; Anders, Nicole; Hammers, Hans J; Dowling, Donna; King, Serina; Antonarakis, Emmanuel S; Drake, Charles G; Eisenberger, Mario A; Denmeade, Samuel R; Rosner, Gary L; Carducci, Michael A

2015-10-01

New therapies are being explored as therapeutic options for men with biochemically recurrent prostate cancer (BRPC) who wish to defer androgen deprivation therapy. MPX is pulverized muscadine grape (Vitis rotundifolia) skin that contains ellagic acid, quercetin, and resveratrol and demonstrates preclinical activity against prostate cancer cells in vitro. In the phase I portion of this phase I/II study, non-metastatic BRPC patients were assigned to increasing doses of MPX (Muscadine Naturals. Inc., Clemmons, NC) in cohorts of two patients, with six patients at the highest dose, using a modified continual reassessment method. Initial dose selection was based on preclinical data showing the equivalent of 500 to 4,000 mg of MPX to be safe in mouse models. The primary endpoint was the recommended phase II dosing regimen. The cohort (n = 14, 71% Caucasian, 29% black) had a median follow-up of 19.2 (6.2-29.7) months, median age of 61 years, and median Gleason score of 7. Four patients had possibly related gastrointestinal symptoms, including grade 1 flatulence, grade 1 soft stools, and grade 1 eructation. No other related adverse events were reported and one patient reported improvement of chronic constipation. Six of 14 patients came off study for disease progression (five metastatic, one rising PSA) after exposure for a median of 15 months. One patient came off for myasthenia gravis that was unrelated to treatment. Seven patients remain on study. The lack of dose-limiting toxicities led to the selection of 4,000 mg/d as the highest dose for further study. Median within-patient PSADT increased by 5.3 months (non-significant, P = 0.17). No patients experienced a maintained decline in serum PSA from baseline. These data suggest that 4,000 mg of MPX is safe, and exploratory review of a lengthening in PSADT of a median of 5.3 months supports further exploration of MPX. Both low-dose (500 mg) and high-dose (4,000 mg) MPX are being further investigated in a randomized, multicenter, placebo-controlled, dose-evaluating phase II trial. © 2015 Wiley Periodicals, Inc.

Oncologic control obtained after radical prostatectomy in men with a pathological Gleason score ≥ 8: a single-center experience.

PubMed

Audenet, François; Comperat, Eva; Seringe, Elise; Drouin, Sarah J; Richard, François; Cussenot, Olivier; Bitker, Marc-Olivier; Rouprêt, Morgan

2011-01-01

To assess the oncologic control afforded by radical prostatectomy (RP) in high-risk prostate cancers with a Gleason score ≥ 8. We performed a retrospective review of prostate cancer patients who underwent RP between 1995 and 2005 for prostate cancer and who had a pathologic Gleason score ≥ 8. Biochemical recurrence was defined as a single rise in PSA levels over 0.2 ng/ml after surgery. Overall, 64 patients were included and followed for a median time of 84.3 months. The mean age was 63 ± 5.2 years. The mean preoperative PSA was 11.9 ± 7.3 ng/ml (1.9-31), and 29 patients (46%) had a PSA > 10 ng/ml. The biopsy Gleason score was ≤ 7 for 49 patients (76.6%). After pathologic analysis, there were 25 (39%) stage pT2, 37 (58%) stage pT3, and 2 (3%) stage pT4 patients. Nine patients had lymph node involvement (14%). The surgical margins were positive in 25 patients (39%). In 51 patients, (80%) the Gleason score was underestimated by biopsies: 40 patients with a definitive score of Gleason 8 had a Gleason score of 6 or 7 on biopsies, while 11 patients with a Gleason score of 9 initially, had a Gleason score of 7 or 8. Twenty-seven patients underwent adjuvant treatment: external radiation therapy (n = 19), HRT (n = 3), or both (n = 5). During follow-up, 41 patients (64%) presented with a biochemical recurrence, and 11 (17%) died. The PSA-free survival rate at five year was 44%. RP remains a possible therapeutic option in certain cases of the high-risk cohort of patients with a Gleason score ≥ 8. However, patients should be warned that surgery might only be the first step of a multi-modal treatment approach. The modalities of adjuvant treatments and the right schedule to deliver it following RP still need to be defined. Copyright © 2011 Elsevier Inc. All rights reserved.

PITX3 promoter methylation is a prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients after radical prostatectomy.

PubMed

Holmes, Emily Eva; Goltz, Diane; Sailer, Verena; Jung, Maria; Meller, Sebastian; Uhl, Barbara; Dietrich, Jörn; Röhler, Magda; Ellinger, Jörg; Kristiansen, Glen; Dietrich, Dimo

2016-01-01

Molecular biomarkers that might help to distinguish between more aggressive and clinically insignificant prostate cancers (PCa) are still urgently needed. Aberrant DNA methylation as a common molecular alteration in PCa seems to be a promising source for such biomarkers. In this study, PITX3 DNA methylation ( mPITX3 ) and its potential role as a prognostic biomarker were investigated. Furthermore, m PITX3 was analyzed in combination with the established PCa methylation biomarker PITX2 ( mPITX2 ). mPITX3 and mPITX2 were assessed by a quantitative real-time PCR and by means of the Infinium HumanMethylation450 BeadChip. BeadChip data were obtained from The Cancer Genome Atlas (TCGA) Research Network. DNA methylation differences between normal adjacent, benign hyperplastic, and carcinomatous prostate tissues were examined in the TCGA dataset as well as in prostatectomy specimens from the University Hospital Bonn. Retrospective analyses of biochemical recurrence (BCR) were conducted in a training cohort ( n  = 498) from the TCGA and an independent validation cohort ( n  = 300) from the University Hospital Bonn. All patients received radical prostatectomy. In PCa tissue, mPITX3 was increased significantly compared to normal and benign hyperplastic tissue. In univariate Cox proportional hazards analyses, mPITX3 showed a significant prognostic value for BCR (training cohort: hazard ratio (HR) = 1.83 (95 % CI 1.07-3.11), p  = 0.027; validation cohort: HR = 2.56 (95 % CI 1.44-4.54), p  = 0.001). A combined evaluation with PITX2 methylation further revealed that hypermethylation of a single PITX gene member (either PITX2 or PITX3 ) identifies an intermediate risk group. PITX3 DNA methylation alone and in combination with PITX2 is a promising biomarker for the risk stratification of PCa patients and adds relevant prognostic information to common clinically implemented parameters. Further studies are required to determine whether the results are transferable to a biopsy-based patient cohort. Trial registration: Patients for this unregistered study were enrolled retrospectively.

Salvage high-intensity focused ultrasound (HIFU) for locally recurrent prostate cancer after failed radiation therapy: Multi-institutional analysis of 418 patients.

PubMed

Crouzet, Sebastien; Blana, Andreas; Murat, Francois J; Pasticier, Gilles; Brown, Stephen C W; Conti, Giario N; Ganzer, Roman; Chapet, Olivier; Gelet, Albert; Chaussy, Christian G; Robertson, Cary N; Thuroff, Stefan; Ward, John F

2017-06-01

To report the oncological outcome of salvage high-intensity focused ultrasound (S-HIFU) for locally recurrent prostate cancer after external beam radiotherapy (EBRT) from a multicentre database. This retrospective study comprises patients from nine centres with local recurrent disease after EBRT treated with S-HIFU from 1995 to 2009. The biochemical failure-free survival (bFFS) rate was based on the 'Phoenix' definition (PSA nadir + 2 ng/mL). Secondary endpoints included progression to metastasis and cancer-specific death. Kaplan-Meier analysis was performed examining overall (OS), cancer-specific (CSS) and metastasis-free survival (MFS). Adverse events and quality of life status are reported. In all, 418 patients with a mean (SD) follow-up of 3.5 (2.5) years were included. The mean (SD) age was 68.6 (5.8) years and the PSA level before S-HIFU was 6.8 (7.8) ng/mL. The median PSA nadir after S-HIFU was 0.19 ng/mL. The OS, CSS and MFS rates at 7 years were 72%, 82% and 81%, respectively. At 5 years the bFFS rate was 58%, 51% and 36% for pre-EBRT low-, intermediate- and high-risk patients, respectively. The 5-year bFFS rate was 67%, 42% and 22% for pre-S-HIFU PSA level ≤4, 4-10 and ≥10 ng/mL, respectively. Complication rates decreased after the introduction of specific post-RT parameters: incontinence (grade II or III) from 32% to 19% (P = 0.002); bladder outlet obstruction or stenosis from 30% to 15% (P = 0.003); recto-urethral fistula decreased from 9% to 0.6% (P < 0.001). Study limitations include being a retrospective analysis from a registry with no control group. S-HIFU for locally recurrent prostate cancer after failed EBRT is associated with 7-year CSS and MFS rates of >80% at a price of significant morbidity. S-HIFU should be initiated early following EBRT failure. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Bladder Carcinoma; Breast Carcinoma; Cervical Carcinoma; Colon Carcinoma; Colorectal Carcinoma; Endometrial Carcinoma; Esophageal Carcinoma; Gastric Carcinoma; Glioma; Head and Neck Carcinoma; Kidney Carcinoma; Liver and Intrahepatic Bile Duct Carcinoma; Lung Carcinoma; Lymphoma; Malignant Uterine Neoplasm; Melanoma; Ovarian Carcinoma; Pancreatic Carcinoma; Plasma Cell Myeloma; Prostate Carcinoma; Rectal Carcinoma; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Cervical Carcinoma; Recurrent Colon Carcinoma; Recurrent Colorectal Carcinoma; Recurrent Esophageal Carcinoma; Recurrent Gastric Carcinoma; Recurrent Glioma; Recurrent Head and Neck Carcinoma; Recurrent Liver Carcinoma; Recurrent Lung Carcinoma; Recurrent Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Plasma Cell Myeloma; Recurrent Prostate Carcinoma; Recurrent Rectal Carcinoma; Recurrent Skin Carcinoma; Recurrent Thyroid Gland Carcinoma; Recurrent Uterine Corpus Carcinoma; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Plasma Cell Myeloma; Skin Carcinoma; Thyroid Gland Carcinoma; Uterine Corpus Cancer

Statin use and risk of disease recurrence and death after radical prostatectomy.

PubMed

Keskiväli, Teemu; Kujala, Paula; Visakorpi, Tapio; Tammela, Teuvo L J; Murtola, Teemu J

2016-04-01

Statins have been linked with improved prostate cancer survival and lower risk of recurrence in men treated with radiation therapy. However, the association is unclear for surgically-treated men. We studied the risk of prostate cancer recurrence and death by statin usage after radical prostatectomy in a cohort of prostate cancer patients treated with radical prostatectomy. A cohort of 1,314 men who underwent curative-intent radical prostatectomy at the Tampere University Hospital, Tampere, Finland during 1995-2009 were linked to national prescription database to obtain detailed information on statin purchases. The risk of PSA recurrence and death (overall and prostate cancer-specific) by statin use before and after the surgery were evaluated using Cox regression with model adjustment for tumor characteristics, total cholesterol and simultaneous use of antidiabetic and antihypertensive drugs. Tissue expression of putative prognostic markers were measured from a subgroup of 323 men. During the median follow-up of 8.6 years after surgery 484 men recurred, while 244 men died (32 due to prostate cancer). In general statin use before or after prostatectomy was not associated with risk of disease recurrence or death. Tissue expression of Ki-67 and ERG modified the association between statin use and risk of disease recurrence; the risk estimates were lower in men with Ki-67 expression above the median (P for interaction 0.001 and 0.004 for statin use before and after prostatectomy, respectively) and no ERG expression in the tumor tissue (P for interaction 0.006 and 0.011). Statin use generally did not affect prostate cancer prognosis after prostatectomy. The effect on disease recurrence may depend on tumor properties, such as proliferation activity. Thus possible future prospective studies should recognize and enroll subgroups of prostate cancer patients most likely to benefit from statins. © 2015 Wiley Periodicals, Inc.

Changes in cerebral metabolic activity in men undergoing androgen deprivation therapy for non-metastatic prostate cancer.

PubMed

Cherrier, M M; Cross, D J; Higano, C S; Minoshima, S

2018-04-27

Androgen deprivation therapy (ADT) is a common treatment option for men with biochemical relapse from prostate cancer. ADT is associated with changes in mood, cognition, and quality of life, and most recently with increased risk for Alzheimer's disease (AD). This study examined changes in brain metabolism using positron emission tomography (PET) in men undergoing intermittent ADT. Nine men with prostate cancer and a rising PSA (biochemical recurrence) without evidence of metastases were treated with intermittent ADT consisting of 9 months of complete androgen blockade achieved with combined leuprolide acetate and flutamide. Patients underwent resting [Fuorine-18] fluorodeoxyglucose PET ( 18 F-FDGPET) at baseline (before treatment) and again after 9 months of ADT. Whole-brain mapping analysis after 9 months of androgen deprivation compared to pretreatment baseline revealed decreased regional cerebral glucose metabolism in the cerebellum, posterior cingulate, and medial thalamus bilaterally. Associations of brain metabolism with measurements of cognition and mood while on androgen deprivation revealed positive correlations between the posterior cingulate, left inferior parietal lobule (BA40), and left mid temporal gyrus (BA39) and spatial reasoning and a negative correlation between left inferior parietal lobule and verbal memory. Several mood indices were negatively correlated with hypothalamus and brainstem. These findings suggest that complete androgen deprivation may result in changes in regional brain metabolism associated with variation in mood, verbal memory, and spatial performance. Brain regions that were impacted from ADT are similar and overlap with brain regions with metabolic decline found in early AD and diabetes, suggesting possible common mechanisms.

Diagnostic accuracy of urinary prostate protein glycosylation profiling in prostatitis diagnosis.

PubMed

Vermassen, Tijl; Van Praet, Charles; Poelaert, Filip; Lumen, Nicolaas; Decaestecker, Karel; Hoebeke, Piet; Van Belle, Simon; Rottey, Sylvie; Delanghe, Joris

2015-01-01

Although prostatitis is a common male urinary tract infection, clinical diagnosis of prostatitis is difficult. The developmental mechanism of prostatitis is not yet unraveled which led to the elaboration of various biomarkers. As changes in asparagine-linked-(N-)-glycosylation were observed between healthy volunteers (HV), patients with benign prostate hyperplasia and prostate cancer patients, a difference could exist in biochemical parameters and urinary N-glycosylation between HV and prostatitis patients. We therefore investigated if prostatic protein glycosylation could improve the diagnosis of prostatitis. Differences in serum and urine biochemical markers and in total urine N-glycosylation profile of prostatic proteins were determined between HV (N=66) and prostatitis patients (N=36). Additionally, diagnostic accuracy of significant biochemical markers and changes in N-glycosylation was assessed. Urinary white blood cell (WBC) count enabled discrimination of HV from prostatitis patients (P<0.001). Urinary bacteria count allowed for discriminating prostatitis patients from HV (P<0.001). Total amount of biantennary structures (urinary 2A/MA marker) was significantly lower in prostatitis patients compared to HV (P<0.001). Combining the urinary 2A/MA marker and urinary WBC count resulted in an AUC of 0.79, 95% confidence interval (CI)=(0.70-0.89) which was significantly better than urinary WBC count (AUC=0.70, 95% CI=[0.59-0.82], P=0.042) as isolated test. We have demonstrated the diagnostic value of urinary N-glycosylation profiling, which shows great potential as biomarker for prostatitis. Further research is required to unravel the developmental course of prostatic inflammation.

Diagnostic accuracy of urinary prostate protein glycosylation profiling in prostatitis diagnosis

PubMed Central

Vermassen, Tijl; Van Praet, Charles; Poelaert, Filip; Lumen, Nicolaas; Decaestecker, Karel; Hoebeke, Piet; Van Belle, Simon; Rottey, Sylvie

2015-01-01

Introduction Although prostatitis is a common male urinary tract infection, clinical diagnosis of prostatitis is difficult. The developmental mechanism of prostatitis is not yet unraveled which led to the elaboration of various biomarkers. As changes in asparagine-linked-(N-)-glycosylation were observed between healthy volunteers (HV), patients with benign prostate hyperplasia and prostate cancer patients, a difference could exist in biochemical parameters and urinary N-glycosylation between HV and prostatitis patients. We therefore investigated if prostatic protein glycosylation could improve the diagnosis of prostatitis. Materials and methods Differences in serum and urine biochemical markers and in total urine N-glycosylation profile of prostatic proteins were determined between HV (N = 66) and prostatitis patients (N = 36). Additionally, diagnostic accuracy of significant biochemical markers and changes in N-glycosylation was assessed. Results Urinary white blood cell (WBC) count enabled discrimination of HV from prostatitis patients (P < 0.001). Urinary bacteria count allowed for discriminating prostatitis patients from HV (P < 0.001). Total amount of biantennary structures (urinary 2A/MA marker) was significantly lower in prostatitis patients compared to HV (P < 0.001). Combining the urinary 2A/MA marker and urinary WBC count resulted in an AUC of 0.79, 95% confidence interval (CI) = (0.70–0.89) which was significantly better than urinary WBC count (AUC = 0.70, 95% CI = [0.59–0.82], P = 0.042) as isolated test. Conclusions We have demonstrated the diagnostic value of urinary N-glycosylation profiling, which shows great potential as biomarker for prostatitis. Further research is required to unravel the developmental course of prostatic inflammation. PMID:26526330

{sup 18}F-Choline Positron Emission Tomography/Computed Tomography and Multiparametric Magnetic Resonance Imaging for the Detection of Early Local Recurrence of Prostate Cancer Initially Treated by Radiation Therapy: Comparison With Systematic 3-Dimensional Transperineal Mapping Biopsy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kanoun, Salim, E-mail: Salim.kanoun@gmail.com; LE2I UMR6306, Centre national de la recherche scientifique, Arts et Métiers, Université Bourgogne Franche-Comté, Dijon; MRI Unit, Centre Hospitalier Régional Universitaire, Hôpital François Mitterrand, Dijon

Purpose: To compare the diagnostic performance of {sup 18}F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT), multiparametric prostate magnetic resonance imaging (mpMRI), and a combination of both techniques for the detection of local recurrence of prostate cancer initially treated by radiation therapy. Methods and Materials: This was a retrospective, single-institution study of 32 patients with suspected prostate cancer recurrence who underwent both FCH-PET/CT and 3T mpMRI within 3 months of one another for the detection of recurrence. All included patients had to be cleared for metastatic recurrence. The reference procedure was systematic 3-dimensional (3D)-transperineal prostate biopsy for the final assessment of local recurrence.more » Both imaging modalities were analyzed by 2 experienced readers blinded to clinical data. The analysis was made per-patient and per-segment using a 4-segment model. Results: The median prostate-specific antigen value at the time of imaging was 2.92 ng/mL. The mean prostate-specific antigen doubling time was 14 months. Of the 32 patients, 31 had a positive 3D-transperineal mapping biopsy for a local relapse. On a patient-based analysis, the detection rate was 71% (22 of 31) for mpMRI and 74% (23 of 31) for FCH-PET/CT. On a segment-based analysis, the sensitivity and specificity were, respectively, 32% and 87% for mpMRI, 34% and 87% for FCH-PET/CT, and 43% and 83% for the combined analysis of both techniques. Accuracy was 64%, 65%, and 66%, respectively. The interobserver agreement was κ = 0.92 for FCH-PET/CT and κ = 0.74 for mpMRI. Conclusions: Both mpMRI and FCH-PET/CT show limited sensitivity but good specificity for the detection of local cancer recurrence after radiation therapy, when compared with 3D-transperineal mapping biopsy. Prostate biopsy still seems to be mandatory to diagnose local relapse and select patients who could benefit from local salvage therapy.« less

Temsirolimus and Vinorelbine Ditartrate in Treating Patients With Unresectable or Metastatic Solid Tumors

ClinicalTrials.gov

2016-06-09

Extensive Stage Small Cell Lung Cancer; Hereditary Paraganglioma; Male Breast Cancer; Malignant Paraganglioma; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Pheochromocytoma; Pancreatic Polypeptide Tumor; Recurrent Breast Cancer; Recurrent Cervical Cancer; Recurrent Endometrial Carcinoma; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Recurrent Neuroendocrine Carcinoma of the Skin; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pheochromocytoma; Recurrent Prostate Cancer; Recurrent Renal Cell Cancer; Recurrent Small Cell Lung Cancer; Recurrent Uterine Sarcoma; Regional Gastrointestinal Carcinoid Tumor; Regional Pheochromocytoma; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage III Neuroendocrine Carcinoma of the Skin; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Prostate Cancer; Stage III Renal Cell Cancer; Stage III Uterine Sarcoma; Stage IIIA Breast Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Breast Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Endometrial Carcinoma; Stage IV Neuroendocrine Carcinoma of the Skin; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IV Uterine Sarcoma; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer; Thyroid Gland Medullary Carcinoma

Recurrence of Lower Urinary Tract Symptoms Following Prostate Artery Embolization for Benign Hyperplasia: Single Center Experience Comparing Two Techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carnevale, Francisco Cesar, E-mail: francisco.carnevale@criep.com.br; Moreira, Airton Mota; Harward, Sardis Honoria

PurposeTo compare recurrence of lower urinary tract symptoms (LUTS) recurrence at 12 months following original prostate artery embolization (oPAE) or “proximal embolization first, then embolize distal” (PErFecTED) PAE for benign prostatic hyperplasia (BPH).Materials and Methods105 consecutive patients older than 45 years, with prostate size greater than 30 cm{sup 3}, International Prostate Symptom Score (IPSS) ≥ 8, quality of life (QoL) index ≥ 3, and refractory status or intolerance of medical management were prospectively enrolled between June 2008 and August 2013. The study was IRB-approved, and all patients provided informed consent. Patients underwent oPAE or PErFecTED PAE and were followed for at least 12 months. Technical success was definedmore » as bilateral embolization and clinical success (non-recurrence) was defined as removal of the Foley catheter in patients with urinary retention, IPSS < 8 and QoL index < 3 at 12 months of follow-up. Nonparametric statistics were used to compare the study groups due to the size of the study population and distributions of clinical data.Results97 patients had 12-month data and were categorized as oPAE without recurrence (n = 46), oPAE with recurrence (n  = 13), PErFecTED without recurrence (n  = 36), or PErFecTED with recurrence (n  = 2). Recurrence was significantly more common in oPAE patients (χ{sup 2}, p = 0.026). Unilateral embolization was significantly associated with recurrence among patients who underwent oPAE (χ{sup 2}, p = 0.032).ConclusionsBoth oPAE and PErFecTED PAE are safe and effective methods for treatment of LUTS, but PErFecTED PAE is associated with a significantly lower rate of symptom recurrence.« less

Salvage Stereotactic Body Radiotherapy for Isolated Lymph Node Recurrent Prostate Cancer: Single Institution Series of 94 Consecutive Patients and 124 Lymph Nodes.

PubMed

Jereczek-Fossa, Barbara Alicja; Fanetti, Giuseppe; Fodor, Cristiana; Ciardo, Delia; Santoro, Luigi; Francia, Claudia Maria; Muto, Matteo; Surgo, Alessia; Zerini, Dario; Marvaso, Giulia; Timon, Giorgia; Romanelli, Paola; Rondi, Elena; Comi, Stefania; Cattani, Federica; Golino, Federica; Mazza, Stefano; Matei, Deliu Victor; Ferro, Matteo; Musi, Gennaro; Nolè, Franco; de Cobelli, Ottavio; Ost, Piet; Orecchia, Roberto

2017-08-01

The purpose of the study was to evaluate the prostate serum antigen (PSA) response, local control, progression-free survival (PFS), and toxicity of stereotactic body radiotherapy (SBRT) for lymph node (LN) oligorecurrent prostate cancer. Between May 2012 and October 2015, 124 lesions were treated in 94 patients with a median dose of 24 Gy in 3 fractions. Seventy patients were treated for a single lesion and 25 for > 1 lesion. In 34 patients androgen deprivation (AD) was combined with SBRT. We evaluated biochemical response according to PSA level every 3 months after SBRT: a 3-month PSA decrease from pre-SBRT PSA of more than 10% identified responder patients. In case of PSA level increase, imaging was performed to evaluate clinical progression. Toxicity was assessed every 6 to 9 months after SBRT. Median follow-up was 18.5 months. In 13 patients (14%) Grade 1 to 2 toxicity was reported without any Grade 3 to 4 toxicity. Biochemical response, stabilization, and progression were observed in 64 (68%), 10 (11%), and 20 (21%) of 94 evaluable patients. Clinical progression was observed in 31 patients (33%) after a median time of 8.1 months. In-field progression occurred in 12 lesions (9.7%). Two-year local control and PFS rates were 84% and 30%, respectively. Age older than 75 years correlated with better biochemical response rate. Age older than 75 years, concomitant AD administered up to 12 months, and pelvic LN involvement correlated with longer PFS. SBRT is safe and offers good in-field control. At 2 years after SBRT, 1 of 3 patients is progression-free. Further investigation is warranted to identify patients who benefit most from SBRT and to define the optimal combination with AD. Copyright © 2017 Elsevier Inc. All rights reserved.

Appraising the relevance of DNA copy number loss and gain in prostate cancer using whole genome DNA sequence data

PubMed Central

Van Loo, Peter; Kay, Jonathan D.; Matthews, Lucy; Haase, Kerstin; Clark, Jeremy; Thomas, Sarah; Butler, Adam P.; Gundem, Gunes; Merson, Sue; Luxton, Hayley; Hawkins, Steve; Ghori, Mohammed; Marsden, Luke; Lambert, Adam; Pelvender, Gill; Massie, Charlie E.; Hazell, Steven; Livni, Naomi; Fisher, Cyril; Ogden, Christopher; Kumar, Pardeep; Thompson, Alan; Nicol, David; Yu, Yongwei; Zhang, Hongwei; Isaacs, William; Visakorpi, Tapio; Verrill, Clare; Lynch, Andrew G.; Lu, Yong Jie; Whitaker, Hayley C.; Neal, David E.; Cooper, Colin S.

2017-01-01

A variety of models have been proposed to explain regions of recurrent somatic copy number alteration (SCNA) in human cancer. Our study employs Whole Genome DNA Sequence (WGS) data from tumor samples (n = 103) to comprehensively assess the role of the Knudson two hit genetic model in SCNA generation in prostate cancer. 64 recurrent regions of loss and gain were detected, of which 28 were novel, including regions of loss with more than 15% frequency at Chr4p15.2-p15.1 (15.53%), Chr6q27 (16.50%) and Chr18q12.3 (17.48%). Comprehensive mutation screens of genes, lincRNA encoding sequences, control regions and conserved domains within SCNAs demonstrated that a two-hit genetic model was supported in only a minor proportion of recurrent SCNA losses examined (15/40). We found that recurrent breakpoints and regions of inversion often occur within Knudson model SCNAs, leading to the identification of ZNF292 as a target gene for the deletion at 6q14.3-q15 and NKX3.1 as a two-hit target at 8p21.3-p21.2. The importance of alterations of lincRNA sequences was illustrated by the identification of a novel mutational hotspot at the KCCAT42, FENDRR, CAT1886 and STCAT2 loci at the 16q23.1-q24.3 loss. Our data confirm that the burden of SCNAs is predictive of biochemical recurrence, define nine individual regions that are associated with relapse, and highlight the possible importance of ion channel and G-protein coupled-receptor (GPCR) pathways in cancer development. We concluded that a two-hit genetic model accounts for about one third of SCNA indicating that mechanisms, such haploinsufficiency and epigenetic inactivation, account for the remaining SCNA losses. PMID:28945760

Appraising the relevance of DNA copy number loss and gain in prostate cancer using whole genome DNA sequence data.

PubMed

Camacho, Niedzica; Van Loo, Peter; Edwards, Sandra; Kay, Jonathan D; Matthews, Lucy; Haase, Kerstin; Clark, Jeremy; Dennis, Nening; Thomas, Sarah; Kremeyer, Barbara; Zamora, Jorge; Butler, Adam P; Gundem, Gunes; Merson, Sue; Luxton, Hayley; Hawkins, Steve; Ghori, Mohammed; Marsden, Luke; Lambert, Adam; Karaszi, Katalin; Pelvender, Gill; Massie, Charlie E; Kote-Jarai, Zsofia; Raine, Keiran; Jones, David; Howat, William J; Hazell, Steven; Livni, Naomi; Fisher, Cyril; Ogden, Christopher; Kumar, Pardeep; Thompson, Alan; Nicol, David; Mayer, Erik; Dudderidge, Tim; Yu, Yongwei; Zhang, Hongwei; Shah, Nimish C; Gnanapragasam, Vincent J; Isaacs, William; Visakorpi, Tapio; Hamdy, Freddie; Berney, Dan; Verrill, Clare; Warren, Anne Y; Wedge, David C; Lynch, Andrew G; Foster, Christopher S; Lu, Yong Jie; Bova, G Steven; Whitaker, Hayley C; McDermott, Ultan; Neal, David E; Eeles, Rosalind; Cooper, Colin S; Brewer, Daniel S

2017-09-01

A variety of models have been proposed to explain regions of recurrent somatic copy number alteration (SCNA) in human cancer. Our study employs Whole Genome DNA Sequence (WGS) data from tumor samples (n = 103) to comprehensively assess the role of the Knudson two hit genetic model in SCNA generation in prostate cancer. 64 recurrent regions of loss and gain were detected, of which 28 were novel, including regions of loss with more than 15% frequency at Chr4p15.2-p15.1 (15.53%), Chr6q27 (16.50%) and Chr18q12.3 (17.48%). Comprehensive mutation screens of genes, lincRNA encoding sequences, control regions and conserved domains within SCNAs demonstrated that a two-hit genetic model was supported in only a minor proportion of recurrent SCNA losses examined (15/40). We found that recurrent breakpoints and regions of inversion often occur within Knudson model SCNAs, leading to the identification of ZNF292 as a target gene for the deletion at 6q14.3-q15 and NKX3.1 as a two-hit target at 8p21.3-p21.2. The importance of alterations of lincRNA sequences was illustrated by the identification of a novel mutational hotspot at the KCCAT42, FENDRR, CAT1886 and STCAT2 loci at the 16q23.1-q24.3 loss. Our data confirm that the burden of SCNAs is predictive of biochemical recurrence, define nine individual regions that are associated with relapse, and highlight the possible importance of ion channel and G-protein coupled-receptor (GPCR) pathways in cancer development. We concluded that a two-hit genetic model accounts for about one third of SCNA indicating that mechanisms, such haploinsufficiency and epigenetic inactivation, account for the remaining SCNA losses.

Focal cryotherapy for localized prostate cancer: a report from the national Cryo On-Line Database (COLD) Registry.

PubMed

Ward, John F; Jones, J Stephen

2012-06-01

Study Type - Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Selective destruction of targeted prostate tissue is now technically feasible. Much has been theorized but little is known about the proper patient selection or treatment outcomes to determine if this organ preserving approach to prostate cancer has merit for further study and diffusion into wider practice. Herein we present the largest retrospective registry report of men treated with sub-total prostate cryotherapy in order to begin to understand how this treatment is being applied despite the paucity of data. •  To identify recent trends in focal cryotherapy from a prospectively maintained treatment registry. •  To describe treatment outcomes after uncontrolled application of focally ablative techniques within community practice. •  We conducted an analysis of the COLD Registry to identify patients treated with partial gland prostate cryoablation between 1997 and 2007. •  Preoperative characteristics and postoperative cancer-specific and functional outcomes were assembled for analysis. •  The COLD Registry contained information for 5853 patients and focal cryotherapy was the codified procedure in 1160 patients (19.8%). •  A dramatic increase in focal treatments was observed, from 46 in 1999 to 567 in 2005 (P < 0.01). •  The biochemical recurrence-free rate (ASTRO definition) at 36 months was 75.7%. •  Prostate biopsy, performed in 164/1160 of patients (14.1%), was positive in 43 (26.3%) of those suspected of cancer recurrence, but in only 3.7% (43/1160) of treated patients. •  Urinary continence (defined as use of 0 pads) was 98.4%. Maintenance of spontaneous erections was 58.1%. Prolonged urinary retention (>30 days) occurred in six (1.1%) patients. Rectourethral fistula was observed in one (0.1%) patient. •  Focal cryoablation is increasingly used for selected patients with prostate cancer. •  Oncological efficacy in the present series appears similar to that of whole-gland cryoablation. •  The impact of focal cryoablation on urinary, sexual and bowel function appears to be less than that of radical therapies, although preservation of sexual function is not as high as might be expected. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

Long-term outcomes in younger men following permanent prostate brachytherapy.

PubMed

Shapiro, Edan Y; Rais-Bahrami, Soroush; Morgenstern, Carol; Napolitano, Barbara; Richstone, Lee; Potters, Louis

2009-04-01

We reviewed the long-term outcomes in men undergoing permanent prostate brachytherapy with a focus on those presenting before age 60 years. Between 1992 and 2005 a total of 2,119 patients with clinical stage T1-T2, N0, M0 prostate cancer treated with permanent prostate brachytherapy were included in this study. Treatment regimens consisted of permanent prostate brachytherapy with or without hormone therapy, permanent prostate brachytherapy with external beam radiotherapy, or all 3 modalities. Biochemical recurrence was defined using the Phoenix definition. Multivariate analysis was performed to determine if age and/or other clinicopathological features were associated with disease progression. The Kaplan-Meier method was used to calculate rates of freedom from progression with the log rank test to compare patients younger than 60 vs 60 years or older. Median followup was 56.1 months. In the study population 237 patients were younger than 60 years at diagnosis (11%). The 5 and 10-year freedom from progression rates were 90.1% and 85.6%, respectively, for the entire population. Multivariate analysis demonstrated that prostate specific antigen (p <0.01), biopsy Gleason score (p <0.0001) and year of treatment (p <0.001) were associated with freedom from progression while age (p = 0.95) and clinical stage (p = 0.11) were not. There was no significant difference in freedom from progression between men younger than 60, or 60 years or older (log rank p = 0.46). In the younger cohort the 10-year freedom from progression for patients presenting with low, intermediate and high risk disease was 91.3%, 80.0% and 70.2% compared to 91.8%, 83.4% and 72.1%, respectively, for men 60 years or older. Our long-term results confirm favorable outcomes after permanent prostate brachytherapy in men younger than 60 years. Outcomes are impacted by disease related risk factors but not by age or clinical stage. Definitive treatment options for younger men with clinically localized prostate cancer should include permanent prostate brachytherapy.

Limited improvement of incorporating primary circulating prostate cells with the CAPRA score to predict biochemical failure-free outcome of radical prostatectomy for prostate cancer.

PubMed

Murray, Nigel P; Aedo, Socrates; Fuentealba, Cynthia; Jacob, Omar; Reyes, Eduardo; Novoa, Camilo; Orellana, Sebastian; Orellana, Nelson

2016-10-01

To establish a prediction model for early biochemical failure based on the Cancer of the Prostate Risk Assessment (CAPRA) score, the presence or absence of primary circulating prostate cells (CPC) and the number of primary CPC (nCPC)/8ml blood sample is detected before surgery. A prospective single-center study of men who underwent radical prostatectomy as monotherapy for prostate cancer. Clinical-pathological findings were used to calculate the CAPRA score. Before surgery blood was taken for CPC detection, mononuclear cells were obtained using differential gel centrifugation, and CPCs identified using immunocytochemistry. A CPC was defined as a cell expressing prostate-specific antigen and P504S, and the presence or absence of CPCs and the number of cells detected/8ml blood sample was registered. Patients were followed up for up to 5 years; biochemical failure was defined as a prostate-specific antigen>0.2ng/ml. The validity of the CAPRA score was calibrated using partial validation, and the fractional polynomial Cox proportional hazard regression was used to build 3 models, which underwent a decision analysis curve to determine the predictive value of the 3 models with respect to biochemical failure. A total of 267 men participated, mean age 65.80 years, and after 5 years of follow-up the biochemical-free survival was 67.42%. The model using CAPRA score showed a hazards ratio (HR) of 5.76 between low and high-risk groups, that of CPC with a HR of 26.84 between positive and negative groups, and the combined model showed a HR of 4.16 for CAPRA score and 19.93 for CPC. Using the continuous variable nCPC, there was no improvement in the predictive value of the model compared with the model using a positive-negative result of CPC detection. The combined CAPRA-nCPC model showed an improvement of the predictive performance for biochemical failure using the Harrell׳s C concordance test and a net benefit on DCA in comparison with either model used separately. The use of primary CPC as a predictive factor based on their presence or absence did not predict aggressive disease or biochemical failure. Although the use of a combined CAPRA-nCPC model improves the prediction of biochemical failure in patients undergoing radical prostatectomy for prostate cancer, this is minimal. The use of the presence or absence of primary CPCs alone did not predict aggressive disease or biochemical failure. Copyright © 2016 Elsevier Inc. All rights reserved.

18F-Choline PET/CT scan in staging and biochemical recurrence in prostate cancer patients: Changes in classification and radiotherapy planning.

PubMed

Cardona Arboniés, J; Rodríguez Alfonso, B; Mucientes Rasilla, J; Martínez Ballesteros, C; Zapata Paz, I; Prieto Soriano, A; Carballido Rodriguez, J; Mitjavila Casanovas, M

To evaluate the role of the 18 F-Choline PET/CT in prostate cancer management when detecting distant disease in planning radiotherapy and staging and to evaluate the therapy changes guided by PET/TC results. A retrospective evaluation was performed on 18 F-Choline PET/CT scans of patients with prostate cancer. Staging and planning radiotherapy scans were selected in patients with at least 9 months follow up. There was a total of 56 studies, 33 (58.93%) for staging, and 23 (41.07%) for planning radiotherapy. All scans were obtained using a hybrid PET/CT scanner. The PET/CT acquisition protocol consisted of a dual-phase procedure after the administration of an intravenous injection of 296-370MBq of 18 F-Choline. There were 43 out of 56 (76.8%) scans considered as positive, and 13 (23.2%) were negative. The TNM staging was changed in 13 (23.2%) scans. The PET/CT findings ruled out distant disease in 4 out of 13 scans, and unknown distant disease was detected in 9 (69.3%) scans. 18 F-Choline PET/CT is a useful technique for detecting unknown distant disease in prostate cancer when staging and planning radiotherapy. The inclusion of 18 F-choline PET/CT should be considered in prostate cancer management protocols. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Cancer/testis antigen SPATA19 is frequently expressed in benign prostatic hyperplasia and prostate cancer.

PubMed

Wong, Kah Keng; Hussain, Faezahtul Arbaeyah; Loo, Suet Kee; López, José I

2017-12-01

Spermatogenesis-associated 19 (SPATA19) is a cancer/testis antigen overexpressed in various cancers. However, its protein expression profile in malignant or non-malignant tissues remains unknown. Thus, in this study, we investigated SPATA19 protein expression patterns in a panel of non-malignant human samples and primary prostate cancer (PCa) with or without benign prostatic hyperplasia (BPH) tissues. SPATA19 was absent in all non-malignant tissues investigated (n=14) except testis and prostate tissues. In terms of malignancies, all PCa cases were positive for SPATA19 exhibiting frequency between 20 and 100% (median 85%) with 63 (52.5%) and 57 (47.5%) cases demonstrating weak/moderate and strong intensities, respectively. Thirty-nine PCa cases (32.5%) contained BPH, and all BPH glands were SPATA19 positive (frequency between 20 and 100%; median 90%) with 13 (33.3%) demonstrating strong SPATA19 expression. Higher SPATA19 expression (higher frequency, intensity, or H-score) was not associated with overall survival or disease-specific survival (DFS) in all PCa cases. However, biochemical recurrence (BR) was associated with worse DFS (p = 0.005) in this cohort of 120 patients, and cases with strong SPATA19 intensity were associated with BR (p = 0.020). In conclusion, we showed that SPATA19 protein was frequently expressed in both BPH and PCa glands, and this warrants future investigations on its pathogenic roles in the disease. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Automatic Identification & Classification of Surgical Margin Status from Pathology Reports Following Prostate Cancer Surgery

PubMed Central

D’Avolio, Leonard W.; Litwin, Mark S.; Rogers, Selwyn O.; Bui, Alex A. T.

2007-01-01

Prostate cancer removal surgeries that result in tumor found at the surgical margin, otherwise known as a positive surgical margin, have a significantly higher chance of biochemical recurrence and clinical progression. To support clinical outcomes assessment a system was designed to automatically identify, extract, and classify key phrases from pathology reports describing this outcome. Heuristics and boundary detection were used to extract phrases. Phrases were then classified using support vector machines into one of three classes: ‘positive (involved) margins,’ ‘negative (uninvolved) margins,’ and ‘not-applicable or definitive.’ A total of 851 key phrases were extracted from a sample of 782 reports produced between 1996 and 2006 from two major hospitals. Despite differences in reporting style, at least 1 sentence containing a diagnosis was extracted from 780 of the 782 reports (99.74%). Of the 851 sentences extracted, 97.3% contained diagnoses. Overall accuracy of automated classification of extracted sentences into the three categories was 97.18%. PMID:18693818

Favorable toxicity and biochemical control using real-time inverse optimization technique for prostate brachytherapy.

PubMed

Raben, Adam; Rusthoven, Kyle E; Sarkar, Abrihup; Glick, Andrew; Benge, Bruce; Jacobs, Dayee; Raben, David

2009-01-01

Favorable dosimetric results have been reported using intraoperative inverse optimization (IO) for permanent prostate brachytherapy. The clinical implications of these improvements in dosimetry are unclear. We review toxicity and early biochemical outcomes for patients implanted using IO technique. Between 2001 and 2007, 165 patients received permanent prostate implants using real-time IO and had >/=3 months of followup. Dose constraints for inverse planning were: the prostate volume receiving 100% of the prescription dose [prostate V(100)] was >95%; the dose received by 90% of the gland [prostate D(90)] was within the 140-180 by dose range; the volume of urethra receiving 150% of the prescription dose [urethra V(150)] was <30%; and the volume of rectal wall receiving 110% of the prescription dose [rectal V(110)] was <1.0 cc. Toxicity was prospectively scored using the Radiation Therapy Oncology Group toxicity scale and the International Prostate Symptom Score questionnaire. Biochemical control was determined using the nadir + 2 ng/mL definition. Mean followup was 30 months (range, 6-63 months). Risk classification was low risk in 89% and intermediate risk in 11%. Iodine-125 sources were used for 161 implants and palladium-103 sources for four implants. The median number of seeds and total activity implanted were 61 and 999 MBq, respectively, for a median prostate volume of 33.6 cc. Late GU and GI morbidity was uncommon. Among patients with at least 24 months followup, 16% had persistent Grade 2-3 urinary morbidity. Grade 2 rectal bleeding occurred in 1 patient (0.6%). Biochemical failure has occurred in only 4 patients at last followup. IO technique for prostate brachytherapy is associated with low rates of late morbidity and excellent early biochemical control. Additionally, the number of seeds and total implanted activity required to achieve a high-quality implant are lower compared with historical controls.

The prognostic value of reactive stroma on prostate needle biopsy: a population-based study.

PubMed

Saeter, Thorstein; Vlatkovic, Ljiljana; Waaler, Gudmund; Servoll, Einar; Nesland, Jahn M; Axcrona, Karol; Axcrona, Ulrika

2015-05-01

Reactive tumor stroma has been shown to play an active role in prostatic carcinogenesis. A grading system for reactive stroma in prostate cancer (PC) has recently been established and found to predict biochemical recurrence and prostate cancer-specific mortality (PCSM) in prostatectomized patients. To the best of our knowledge, there has been no study investigating the prognostic value of reactive stromal grading (RSG) with regard to PCSM when evaluated in diagnostic prostate needle biopsies. A population-based study on 318 patients, encompassing all cases of PC diagnosed by needle biopsies and without evidence of systemic metastasis at the time of diagnosis in Aust-Agder County in the period 1991-1999. Patients were identified by cross-referencing the Cancer Registry of Norway. Clinical data were obtained by review of medical charts. The endpoint was PCSM. RSG was evaluated on haematoxylin and eosin stained sections according to previously described criteria; grade 0, 0-5% reactive stroma; grade 1, 6-15%; grade 2, 16-50%; grade 3, 51-100%. RSG could be evaluated in 278 patients. The median follow- up time was 110 months (interquartile range: 51-171). The 10-year PC - specific survival rate for RSGs of 0, 1, 2, and 3 was 96%, 81%, 69%, and 63%, respectively (P < 0.005). RSG remained independently associated with PCSM in a multivariate Cox regression analysis adjusting for prostate-specific antigen level, clinical stage, Gleason score, and mode of treatment. The concordance index of the multivariate model was 0.814 CONCLUSIONS: Our study demonstrates that RSG in diagnostic prostate needle biopsies predicts PCSM independently of other evaluable prognostic factors. Hence, RSG could be used in addition to traditional prognostic factors for prognostication and treatment stratification of PC patients. © 2015 Wiley Periodicals, Inc.

Gemcitabine Hydrochloride and Cisplatin With or Without Bevacizumab in Treating Patients With Advanced Urinary Tract Cancer

ClinicalTrials.gov

2018-06-11

Bladder Urothelial Carcinoma; Distal Urethral Carcinoma; Infiltrating Bladder Urothelial Carcinoma Associated With Urethral Carcinoma; Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Proximal Urethral Carcinoma; Recurrent Bladder Carcinoma; Recurrent Prostate Carcinoma; Recurrent Urethral Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Regional Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage IV Bladder Cancer AJCC v7; Stage IV Prostate Cancer AJCC v7; Stage IV Urethral Cancer AJCC v7; Ureter Carcinoma

Recurrent Prostate Infection: What Are the Treatment Options?

MedlinePlus

... recurring prostate infection, also known as chronic bacterial prostatitis, is typically treated with antibiotics. This type of ... Erik P. Castle, M.D. Pontari M. Chronic prostatitis/chronic pelvic pain syndrome. https://www.uptodate.com/ ...

Local recurrence of prostate cancer after radical prostatectomy is at risk to be missed in 68Ga-PSMA-11-PET of PET/CT and PET/MRI: comparison with mpMRI integrated in simultaneous PET/MRI.

PubMed

Freitag, Martin T; Radtke, Jan P; Afshar-Oromieh, Ali; Roethke, Matthias C; Hadaschik, Boris A; Gleave, Martin; Bonekamp, David; Kopka, Klaus; Eder, Matthias; Heusser, Thorsten; Kachelriess, Marc; Wieczorek, Kathrin; Sachpekidis, Christos; Flechsig, Paul; Giesel, Frederik; Hohenfellner, Markus; Haberkorn, Uwe; Schlemmer, Heinz-Peter; Dimitrakopoulou-Strauss, A

2017-05-01

The positron emission tomography (PET) tracer 68 Ga-PSMA-11, targeting the prostate-specific membrane antigen (PSMA), is rapidly excreted into the urinary tract. This leads to significant radioactivity in the bladder, which may limit the PET-detection of local recurrence (LR) of prostate cancer (PC) after radical prostatectomy (RP), developing in close proximity to the bladder. Here, we analyze if there is additional value of multi-parametric magnetic resonance imaging (mpMRI) compared to the 68 Ga-PSMA-11-PET-component of PET/CT or PET/MRI to detect LR. One hundred and nineteen patients with biochemical recurrence after prior RP underwent both hybrid 68 Ga-PSMA-11-PET/CT low-dose (1 h p.i.) and -PET/MRI (2-3 h p.i.) including a mpMRI protocol of the prostatic bed. The comparison of both methods was restricted to the abdomen with focus on LR (McNemar). Bladder-LR distance and recurrence size were measured in axial T2w-TSE. A logistic regression was performed to determine the influence of these variables on detectability in 68 Ga-PSMA-11-PET. Standardized-uptake-value (SUV mean ) quantification of LR was performed. There were 93/119 patients that had at least one pathologic finding. In addition, 18/119 Patients (15.1%) were diagnosed with a LR in mpMRI of PET/MRI but only nine were PET-positive in PET/CT and PET/MRI. This mismatch was statistically significant (p = 0.004). Detection of LR using the PET-component was significantly influenced by proximity to the bladder (p = 0.028). The PET-pattern of LR-uptake was classified into three types (1): separated from bladder; (2): fuses with bladder, and (3): obliterated by bladder). The size of LRs did not affect PET-detectability (p = 0.84), mean size was 1.7 ± 0.69 cm long axis, 1.2 ± 0.46 cm short-axis. SUV mean in nine men was 8.7 ± 3.7 (PET/CT) and 7.0 ± 4.2 (PET/MRI) but could not be quantified in the remaining nine cases (obliterated by bladder). The present study demonstrates additional value of hybrid 68 Ga-PSMA-11-PET/MRI by gaining complementary diagnostic information compared to the 68 Ga-PSMA-11-PET/CT low-dose for patients with LR of PC.

3+4 = 6? Implications of the stratification of localised Gleason 7 prostate cancer by number and percentage of positive biopsy cores in selecting patients for active surveillance.

PubMed

Ruiz-Cerdá, J L; Lorenzo Soriano, L; Ramos-Soler, D; Marzullo-Zucchet, L; Loras Monfort, A; Boronat Tormo, F

2018-03-01

To determine whether the number and percentage of positive biopsy cores identify a Gleason 3+4 prostate cancer (PC) subgroup of similar biologic behaviour to Gleason 3+3. An observational post-radical prostatectomy study was conducted of a cohort of 799 patients with localised low-risk (n=582, Gleason 6, PSA <10ng/ml and cT1c-2a) and favourable intermediate PC (n=217, Gleason 3+4, PSA ≤10 ng/ml and pT2abc). The Gleason 3+4 tumours were stratified by number (≤3 vs.>3) and by percentage of positive cores (≤33% vs. >33%). We analysed the tumours' association with the biochemical recurrence risk (BRR) and cancer-specific mortality (CSM). We conducted various predictive models using Cox regression and estimated (C-index) and compared their predictive capacity. With a median follow-up of 71 months, the BRR and CSM of the patient group with Gleason 3+4 tumours and a low number (≤3) and percentage (≤33%) of positive cores were not significantly different from those of the patients with Gleason 6 tumours. At 5 and 10 years, there were no significant differences in the number of biochemical recurrences, the probability of remaining free of biochemical recurrences, the number of deaths by PC or the probability of death by PC between the 2 groups. In contrast, the patients with Gleason 3+4 tumours and more than 33% of positive cores presented more deaths by PC than the patients with Gleason 6 tumours. At 10 years, the probability of CSM was significantly greater. This subgroup of tumours showed a significantly greater BRR (RR, 1.6; P=.02) and CSM (RR, 5.8, P≤.01) compared with the Gleason 6 tumours. The model with Gleason 3+4 stratified by the percentage of positive cores significantly improved the predictive capacity of BRR and CSM. Fewer than 3 cores and a percentage <33% of positive cores identifies a subgroup of Gleason 3+4 tumours with biological behaviour similar to Gleason 6 tumours. At 10 years, there were no differences in BRR and CSM between the 2 groups. These results provide evidence supporting active surveillance as an alternative for Gleason 3+4 tumours and low tumour extension in biopsy. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Mature Results of the Ottawa Phase II Study of Intermittent Androgen-Suppression Therapy in Prostate Cancer: Clinical Predictors of Outcome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malone, Shawn; Perry, Gad; Eapen, Libni

2007-07-01

Purpose: To present the mature experience of a phase II trial of intermittent androgen suppression (IAS). Methods and Materials: Intermittent androgen-suppression therapy was initiated in prostate-cancer patients to delay hormone resistance and minimize potential side effects of androgen-deprivation therapy (ADT). Patients received cyclical periods of ADT and observation (off-treatment interval [OTI]). Androgen-deprivation therapy was reinitiated when the level of prostate-specific antigen (PSA) rose above 10 ng/ml, or for disease progression. Associations between clinical factors and eligibility for OTI were measured. Kaplan-Meier and Cox regression analyses were used to determine factors predicting the duration of OTIs. Results: Ninety-five patients completed 187more » cycles of treatment. The median duration of OTIs was 8.5 months. Patients with higher PSA and metastatic disease were less likely to be eligible for the first OTI (p < 0.01). In multivariate analysis, patients with higher PSA and local relapse had significantly longer OTIs (p < 0.01) compared with metastatic patients. The median time to withdrawal from the study was 37 months. Conclusions: Intermittent androgen suppression appears to be a favorable treatment option for patients with biochemically (according to level of PSA) or locally recurrent prostate cancer with favorable long-term survival, a high probability of eligibility for OTIs, and durable OTIs.« less

The prognostic significance of the 2014 International Society of Urological Pathology (ISUP) grading system for prostate cancer.

PubMed

Samaratunga, Hemamali; Delahunt, Brett; Gianduzzo, Troy; Coughlin, Geoff; Duffy, David; LeFevre, Ian; Johannsen, Shulammite; Egevad, Lars; Yaxley, John

2015-10-01

The 2005 International Society of Urological Pathology (ISUP) modified Gleason grading system was further amended in 2014 with the establishment of grade groupings (ISUP grading). This study examined the predictive value of ISUP grading, comparing results with recognised prognostic parameters.Of 3700 men undergoing radical prostatectomy (RP) reported at Aquesta Pathology between 2008 and 2013, 2079 also had a positive needle biopsy available for review. We examined the association between needle biopsy 2014 ISUP grade and 2005 modified Gleason score, tumour volume, pathological stage of the subsequent RP tumour, as well as biochemical recurrence-free survival (BRFS). The median age was 62 (range 32-79 years). Median serum prostate specific antigen was 5.9 (range 0.4-69 ng/mL). For needle biopsies, 280 (13.5%), 1031 (49.6%), 366 (17.6%), 77 (3.7%) and 325 (15.6%) were 2014 ISUP grades 1-5, respectively. Needle biopsy 2014 ISUP grade showed a significant association with RP tumour volume (p < 0.001), TNM pT and N stage (p < 0.001) and BRFS (p < 0.001). Multivariate analysis using Cox proportional hazards regression model showed serum prostate specific antigen (PSA) at the time of diagnosis and ISUP grade >2 to be significantly associated with BRFS.This study provides evidence of the prognostic significance of ISUP grading for thin core needle biopsy of prostate.

Outcomes after radical prostatectomy for patients with clinical stages T1-T2 prostate cancer with pathologically positive lymph nodes in the prostate-specific antigen era.

PubMed

Dorin, Ryan P; Lieskovsky, Gary; Fairey, Adrian S; Cai, Jie; Daneshmand, Siamak

2013-11-01

To evaluate the outcomes of radical prostatectomy (RP) and pelvic lymph node dissection (PLND) for clinically organ confined prostate cancer (CaP) with regional lymph node metastases (pN1) treated in the era of prostate-specific antigen (PSA) screening. A single institution cohort of 2,487 men with cT1-T2 CaP treated with open radical prostatectomy and pelvic lymph node dissection between 1988 and 2008 were analyzed. Kaplan-Meier and Cox proportional regression models were used to analyze overall survival (OS), clinical recurrence-free survival (cRFS), and biochemical recurrence-free survival (bRFS). Overall, 150 out of 2,487 patients (6%) had pN1 disease, with a median follow-up of 10.4 years. The predicted 10-year OS, cRFS, and bRFS rates for patients with pN0 and pN1 were 86% and 74% (Log rank P < 0.001), 97% and 84% (Log rank P < 0.001), and 88% and 57% (Log rank P < 0.001), respectively. In the subset of pN1 patients treated with surgery only (n = 49), the predicted 10-year OS, cRFS, and bRFS rates were 81%, 80%, and 59%, respectively. Exploratory univariate regression analysis showed that age (P = 0.003), total number of lymph nodes identified (P = 0.040), and total number of positive lymph nodes identified (P = 0.004) were associated with OS. Total number of positive lymph nodes (LNs) identified was also significantly associated with cRFS (P = 0.05). The incidence of pN1 in patients with cT1-T2 CaP treated with surgery in the era of PSA screening was low. RP and PLND demonstrated therapeutic efficacy in a subset of pN1 patients treated with surgery alone. Copyright © 2013 Elsevier Inc. All rights reserved.

Prostate specific antigen bounce is related to overall survival in prostate brachytherapy.

PubMed

Hinnen, Karel A; Monninkhof, Evelyn M; Battermann, Jan J; van Roermund, Joep G H; Frank, Steven J; van Vulpen, Marco

2012-02-01

To investigate the association between prostate specific antigen (PSA) bounce and disease outcome after prostate brachytherapy. We analyzed 975 patients treated with (125)I implantation monotherapy between 1992 and 2006. All patients had tumor Stage ≤ 2c, Gleason score ≤ 7 prostate cancer, a minimum follow-up of 2 years with at least four PSA measurements, and no biochemical failure in the first 2 years. Median follow-up was 6 years. Bounce was defined as a PSA elevation of +0.2 ng/mL with subsequent decrease to previous nadir. We used the Phoenix +2 ng/mL definition for biochemical failure. Additional endpoints were disease-specific and overall survival. Multivariate Cox regression analysis was performed to adjust for potential confounding factors. Bounce occurred in 32% of patients, with a median time to bounce of 1.6 years. More than 90% of bounces took place in the first 3 years after treatment and had disappeared within 2 years of onset. Ten-year freedom from biochemical failure, disease-specific survival, and overall survival rates were, respectively, 90%, 99%, and 88% for the bounce group and 70%, 93%, and 82% for the no-bounce group. Only 1 patient (0.3%) died of prostate cancer in the bounce group, compared with 40 patients (6.1%) in the no-bounce group. Adjusted for confounding, a 70% biochemical failure risk reduction was observed for patients experiencing a bounce (hazard ratio 0.31; 95% confidence interval 0.20-0.48). A PSA bounce after prostate brachytherapy is strongly related to better outcome in terms of biochemical failure, disease-specific survival, and overall survival. Copyright © 2012 Elsevier Inc. All rights reserved.

Metformin Has a Positive Therapeutic Effect on Prostate Cancer in Diabetes Mellitus 2 Patients

PubMed Central

Chong, R. William; Vasudevan, Vijaya; Zuber, Jeffrey; Solomon, Solomon S.

2016-01-01

Objective Prostate cancer and type 2 diabetes mellitus are both common diseases found in the elderly male population. The diabetic drug, metformin, has been shown to have anti-neoplastic properties and demonstrated better treatment outcomes when used as adjuvant therapy in breast cancer patients. The hormonally-sensitive cancer analogous to breast in men is prostate. We investigated improved survival, lower risks of recurrences, and lower, more stable levels of prostate specific antigen (PSA) in DM2 patients with prostate cancer on metformin. Methods Prostate cancer patients with type 2 diabetes that remained on metformin were compared to controls not on metformin matched by age, weight, race, and Gleason score cancer staging. The endpoints of our study included final PSA values, number of recurrences, metastases and number living for each group. Results There were significantly fewer deaths (23% vs 10%), fewer recurrences (15% vs 8%), and fewer metastases (5% vs 0%), and fewer secondary cancers (17% vs 6%) in the metformin group (p<0.004). The final PSA value was lower in the metformin-treated group with a result approaching significance (p=0.067). The primary treatments for prostate cancer (i.e. surgery, radiation, androgen depletion) were found to be comparable in both groups. Conclusions Our retrospective study shows that adjuvant metformin therapy leads to a better prognosis in prostate cancer. Not only are PSA levels controlled for several years, but there are significantly fewer cancer recurrences in metformin treated patients. Overall, these results are promising and should be followed up with a prospective study to assess long-term survival. PMID:27079349

Decreased immunostaining for macrophage scavenger receptor is associated with poor prognosis of prostate cancer.

PubMed

Takayama, Hitoshi; Nonomura, Norio; Nishimura, Kazuo; Oka, Daizo; Shiba, Masahiro; Nakai, Yasutomo; Nakayama, Masashi; Tsujimura, Akira; Aozasa, Katsuyuki; Okuyama, Akihiko

2009-02-01

The aim of this study is to evaluate the expression of the macrophage scavenger receptor (MSR) in prostate needle biopsy specimens as a possible prognostic factor for prostate cancer. As MSR reportedly has a role in recognizing foreign pathogenic substances, MSR-positive inflammatory cells are often detected in solid tumours, and there is a correlation between the relative risk of prostate cancer and polymorphism of the MSR gene. MSR was evaluated by immunostaining in needle biopsies of the prostate from 135 patients who were confirmed to have prostate cancer. Among these men, 70 were treated by radical prostatectomy or by radiotherapy as definitive therapy; the other 65 were treated by hormonal therapy because of advanced disease or age. Needle-biopsy specimens were sectioned at 5 microm and immunostained with a monoclonal antibody against MSR. Six microscopic (x400) fields around the cancer foci were selected in each case for analysis. The median number of MSR-positive cells (MSR count) in each case was 24. There was an inverse correlation between the MSR count and Gleason score and clinical stage. The MSR count was lower in patients with biochemical (prostate-specific antigen, PSA) failure than that in those with no PSA failure (P < 0.001). In all patients, the recurrence-free survival (RFS) rate was significantly higher in those with a high MSR count (> or =24) than that in those with low MSR count (<24, P < 0.001). Moreover, for patients treated by definitive or hormonal therapy, the RFS rates in those with a higher MSR count were higher than in those with a lower MSR count (P < 0.001 and 0.014, respectively). Cox multivariate analysis showed that the MSR count was a prognostic factor for prostate cancer in addition to extraprostatic extension and Gleason score (P = 0.002, 0.038 and 0.011, respectively). The results of immunostaining of MSR in needle-biopsy specimens is a prognostic factor for prostate cancer.

Feasibility of minimally invasive radical prostatectomy in prostate cancer patients with high prostate-specific antigen: feasibility and 1-year outcomes.

PubMed

Do, Minh; Ragavan, Narasimhan; Dietel, Anja; Liatsikos, Evangelos; Anderson, Chris; McNeill, Alan; Stolzenburg, Jens-Uwe

2012-10-01

Urologists are cautious to offer minimally invasive radical prostatectomy in prostate cancer patients with high prostate-specific antigen (and therefore anticipated to have locally advanced or metastatic disease) because of concerns regarding lack of complete cure after minimally invasive radical prostatectomy and of worsening of continence if adjuvant radiotherapy is used. A retrospective review of our institutional database was carried out to identify patients with PSA ≥20 ng/mL who underwent minimally invasive radical prostatectomy between January 2002 and October 2010. Intraoperative, pathological, functional and short-term oncological outcomes were assessed. Overall, 233 patients met study criteria and were included in the analysis. The median prostate-specific antigen and prostate size were 28.5 ng/mL and 47 mL, respectively. Intraoperative complications were the following: rectal injury (0.86%) and blood transfusion (1.7%). Early postoperative complications included prolonged (>6 days) catheterization (9.4%), hematoma (4.7%), deep venous thrombosis (0.86%) and lymphocele (5.1%). Late postoperative complications included cerebrovascular accident (0.4%) and anastomotic stricture (0.8%). Pathology revealed poorly differentiated cancer in 48.9%, pT3/pT4 disease in 55.8%, positive margins in 28.3% and lymph node disease in 20.2% of the cases. Adverse pathological findings were more frequent in patients with prostate-specific antigen >40 ng/mL and (or) in those with locally advanced disease (pT3/pT4). In 62.2% of the cases, adjuvant radiotherapy was used. At 1-year follow up, 80% of patients did not show evidence of biochemical recurrence and 98.8% of them had good recovery of continence. Minimally invasive radical prostatectomy might represent a reasonable option in prostate cancer patients with high prostate-specific antigen as a part of a multimodality treatment approach. © 2012 The Japanese Urological Association.

Race and risk of metastases and survival after radical prostatectomy: Results from the SEARCH database.

PubMed

Freedland, Stephen J; Vidal, Adriana C; Howard, Lauren E; Terris, Martha K; Cooperberg, Matthew R; Amling, Christopher L; Kane, Christopher J; Aronson, William J

2017-11-01

Black race is associated with prostate cancer (PC) diagnosis and poor outcome. Previously, the authors reported that black men undergoing radical prostatectomy (RP) in equal-access hospitals had an increased risk of biochemical disease recurrence (BCR), but recurrences were equally aggressive as those occurring in white men. The authors examined the association between race and long-term outcomes after RP. Data regarding 1665 black men (37%) and 2791 white men (63%) undergoing RP were analyzed. Using Cox models, the authors tested the association between race and BCR, BCR with a prostate-specific antigen (PSA) doubling time <9 months (aggressive disease recurrence), metastases, PC-specific death, and overall death. At a median follow-up of 102 months, 1566 men (35%) developed BCR, 217 men (5%) experienced aggressive disease recurrence, 193 men (4%) developed metastases, and 1207 men (27%) had died, 107 of whom (2%) died of PC. White men were older and had a lower preoperative PSA level, a lower biopsy and pathological grade group, and more capsular penetration but less seminal vesicle invasion and positive surgical margins versus black men (all P<.05). Black men were found to have a more recent surgery year (P<.001). On univariable analysis, black race was associated with increased BCR (P = .003) and reduced overall death (P = .017). On multivariable analysis, black race was not found to be associated with BCR (hazard ratio [HR], 1.07; P = .26), aggressive recurrence (HR, 1.14; P = .42), metastasis (HR, 1.24; P = .21), PC-specific death (HR, 1.03; P = .91), or overall death (HR, 1.03; P = .67). Among men undergoing RP at equal-access centers, although black men were found to have an increased risk of BCR, they had similar risks of aggressive disease recurrence, metastasis, and PC-specific death compared with white men, and the risk of BCR was found to be similar after controlling for risk parameters. Longer follow-up is needed to confirm these findings. Cancer 2017;123:4199-4206. © 2017 American Cancer Society. © 2017 American Cancer Society.

Hemi salvage high-intensity focused ultrasound (HIFU) in unilateral radiorecurrent prostate cancer: a prospective two-centre study.

PubMed

Baco, Eduard; Gelet, Albert; Crouzet, Sébastien; Rud, Erik; Rouvière, Olivier; Tonoli-Catez, Hélène; Berge, Viktor; Chapelon, Jean-Yves; Eggesbø, Heidi B

2014-10-01

To report the oncological and functional outcomes of hemi salvage high-intensity focused ultrasound (HSH) in patients with unilateral radiorecurrent prostate cancer. Between 2009 and 2012, 48 patients were prospectively enrolled in two European centres. Inclusion criteria were biochemical recurrence (BCR) after primary radiotherapy (RT), positive magnetic resonance imaging and ≥1 positive biopsy in only one lobe. BCR was defined using Phoenix criteria (a rise by ≥2 ng/mL above the nadir prostate specific antigen [PSA] level). The following schemes and criteria for functional outcomes were used: Ingelman-Sundberg score using International Continence Society (ICS) questionnaire (A and B), International prostate symptom score (IPSS), International Index of Erectile Function-5 (IIEF-5) points, the European Organisation for the Research and Treatment of Cancer (EORTC) quality of life questionnaires (QLQ C-30). HSH was performed under spinal or general anaesthesia using the Ablatherm® Integrated Imaging device. Patients with obstructive voiding symptoms at the time of treatment underwent an endoscopic bladder neck resection or incision during the same anaesthesia to prevent the risk of postoperative obstruction. After HSH the mean (sd) PSA nadir was 0.69 (0.83) ng/mL at a median (interquartile range) follow-up of 16.3 (10.5-24.5) months. Disease progression occurred in 16/48 (33%). Of these, four had local recurrence in the untreated lobe and four bilaterally, six developed metastases, and two had rising PSA levels without local recurrence or radiological confirmed metastasis. Progression-free survival rates at 12, 18, and 24 months were 83%, 64%, and 52%. Severe incontinence occurred in four of the 48 patients (8%), eight (17%) required one pad a day, and 36/48 (75%) were pad-free. The ICS questionnaire showed a mean (sd) deterioration from 0.7 (2.0) to 2.3 (4.5) for scores A and 0.6 (1.4) to 1.6 (3.0) for B. The mean (sd) IPSS and erectile function (IIEF-5) scores decreased from a mean (sd) of 7.01 (5.6) to 8.6 (5.1) and from 11.2 (8.6) to 7.0 (5.8), respectively. The mean (sd) EORTC QLC-30 scores before and after HSH were 35.7 (8.6) vs 36.8 (8.6). HSH is a feasible therapeutic option in patients with unilateral radiorecurrent prostate cancer, which offers limited urinary and rectal morbidity, and preserves health-related quality of life. © 2013 The Authors. BJU International © 2013 BJU International.

Predicting survival of men with recurrent prostate cancer after radical prostatectomy.

PubMed

Dell'Oglio, Paolo; Suardi, Nazareno; Boorjian, Stephen A; Fossati, Nicola; Gandaglia, Giorgio; Tian, Zhe; Moschini, Marco; Capitanio, Umberto; Karakiewicz, Pierre I; Montorsi, Francesco; Karnes, R Jeffrey; Briganti, Alberto

2016-02-01

To develop and externally validate a novel nomogram aimed at predicting cancer-specific mortality (CSM) after biochemical recurrence (BCR) among prostate cancer (PCa) patients treated with radical prostatectomy (RP) with or without adjuvant external beam radiotherapy (aRT) and/or hormonal therapy (aHT). The development cohort included 689 consecutive PCa patients treated with RP between 1987 and 2011 with subsequent BCR, defined as two subsequent prostate-specific antigen values >0.2 ng/ml. Multivariable competing-risks regression analyses tested the predictors of CSM after BCR for the purpose of 5-year CSM nomogram development. Validation (2000 bootstrap resamples) was internally tested. External validation was performed into a population of 6734 PCa patients with BCR after treatment with RP at the Mayo Clinic from 1987 to 2011. The predictive accuracy (PA) was quantified using the receiver operating characteristic-derived area under the curve and the calibration plot method. The 5-year CSM-free survival rate was 83.6% (confidence interval [CI]: 79.6-87.2). In multivariable analyses, pathologic stage T3b or more (hazard ratio [HR]: 7.42; p = 0.008), pathologic Gleason score 8-10 (HR: 2.19; p = 0.003), lymph node invasion (HR: 3.57; p = 0.001), time to BCR (HR: 0.99; p = 0.03) and age at BCR (HR: 1.04; p = 0.04), were each significantly associated with the risk of CSM after BCR. The bootstrap-corrected PA was 87.4% (bootstrap 95% CI: 82.0-91.7%). External validation of our nomogram showed a good PA at 83.2%. We developed and externally validated the first nomogram predicting 5-year CSM applicable to contemporary patients with BCR after RP with or without adjuvant treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

18F-fluorocholine PET-guided target volume delineation techniques for partial prostate re-irradiation in local recurrent prostate cancer.

PubMed

Wang, Hui; Vees, Hansjörg; Miralbell, Raymond; Wissmeyer, Michael; Steiner, Charles; Ratib, Osman; Senthamizhchelvan, Srinivasan; Zaidi, Habib

2009-11-01

We evaluate the contribution of (18)F-choline PET/CT in the delineation of gross tumour volume (GTV) in local recurrent prostate cancer after initial irradiation using various PET image segmentation techniques. Seventeen patients with local-only recurrent prostate cancer (median=5.7 years) after initial irradiation were included in the study. Rebiopsies were performed in 10 patients that confirmed the local recurrence. Following injection of 300 MBq of (18)F-fluorocholine, dynamic PET frames (3 min each) were reconstructed from the list-mode acquisition. Five PET image segmentation techniques were used to delineate the (18)F-choline-based GTVs. These included manual delineation of contours (GTV(man)) by two teams consisting of a radiation oncologist and a nuclear medicine physician each, a fixed threshold of 40% and 50% of the maximum signal intensity (GTV(40%) and GTV(50%)), signal-to-background ratio-based adaptive thresholding (GTV(SBR)), and a region growing (GTV(RG)) algorithm. Geographic mismatches between the GTVs were also assessed using overlap analysis. Inter-observer variability for manual delineation of GTVs was high but not statistically significant (p=0.459). In addition, the volumes and shapes of GTVs delineated using semi-automated techniques were significantly higher than those of GTVs defined manually. Semi-automated segmentation techniques for (18)F-choline PET-guided GTV delineation resulted in substantially higher GTVs compared to manual delineation and might replace the latter for determination of recurrent prostate cancer for partial prostate re-irradiation. The selection of the most appropriate segmentation algorithm still needs to be determined.

Effects of perineural invasion on biochemical recurrence and prostate cancer-specific survival in patients treated with definitive external beam radiotherapy.

PubMed

Peng, Luke C; Narang, Amol K; Gergis, Carol; Radwan, Noura A; Han, Peijin; Marciscano, Ariel E; Robertson, Scott P; He, Pei; Trieu, Janson; Ram, Ashwin N; McNutt, Todd R; Griffith, Emily; DeWeese, Theodore A; Honig, Stephanie; Singh, Harleen; Greco, Stephen C; Tran, Phuoc T; Deville, Curtiland; DeWeese, Theodore L; Song, Daniel Y

2018-06-01

Perineural invasion (PNI) has not yet gained universal acceptance as an independent predictor of adverse outcomes for prostate cancer treated with external beam radiotherapy (EBRT). We analyzed the prognostic influence of PNI for a large institutional cohort of prostate cancer patients who underwent EBRT with and without androgen deprivation therapy (ADT). We, retrospectively, reviewed prostate cancer patients treated with EBRT from 1993 to 2007 at our institution. The primary endpoint was biochemical failure-free survival (BFFS), with secondary endpoints of metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS). Univariate and multivariable Cox proportional hazards models were constructed for all survival endpoints. Hazard ratios for PNI were analyzed for the entire cohort and for subsets defined by NCCN risk level. Additionally, Kaplan-Meier survival curves were generated for all survival endpoints after stratification by PNI status, with significant differences computed using the log-rank test. Of 888 men included for analysis, PNI was present on biopsy specimens in 187 (21.1%). PNI was associated with clinical stage, pretreatment PSA level, biopsy Gleason score, and use of ADT (all P<0.01). Men with PNI experienced significantly inferior 10-year BFFS (40.0% vs. 57.8%, P = 0.002), 10-year MFS (79.7% vs. 89.0%, P = 0.001), and 10-year PCSS (90.9% vs. 95.9%, P = 0.009), but not 10-year OS (67.5% vs. 77.5%, P = 0.07). On multivariate analysis, PNI was independently associated with inferior BFFS (P<0.001), but not MFS, PCSS, or OS. In subset analysis, PNI was associated with inferior BFFS (P = 0.04) for high-risk patients and with both inferior BFFS (P = 0.01) and PCSS (P = 0.05) for low-risk patients. Biochemical failure occurred in 33% of low-risk men with PNI who did not receive ADT compared to 8% for low-risk men with PNI treated with ADT (P = 0.01). PNI was an independently significant predictor of adverse survival outcomes in this large institutional cohort, particularly for patients with NCCN low-risk disease. PNI should be carefully considered along with other standard prognostic factors when treating these patients with EBRT. Supplementing EBRT with ADT may be beneficial for select low-risk patients with PNI though independent validation with prospective studies is recommended. Copyright © 2018 Elsevier Inc. All rights reserved.

HIFU therapy for local recurrence of prostate cancer after external beam radiotherapy and radical prostatectomy - 5,5 years experience

NASA Astrophysics Data System (ADS)

Solovov, V. A.; Vozdvizhenskiy, M. O.; Matysh, Y. S.

2017-03-01

Objectives. To evaluate the clinical efficacy of high-intensity focused ultrasound ablation (HIFU) for local recurrence of prostate cancer after external beam radiotherapy (EBRT) and radical prostatectomy (RPE). Materials and Methods: During 2007-2013 years 47 patients with local recurrence of prostate cancer after EBRT and RPE undertook HIFU therapy on the system "Ablaterm» (EDAP, France). Relapse arose after an average of 2 years after EBRT and RPE. Median follow-up after HIFU therapy was 38 (12-60) months. The mean age was 68.5 ± 5.8 years. The median PSA level before HIFU - 15.4 (7-48) ng / mL. Results: In 34 patients (72.3%) at six months after treatment the median PSA was 0.4 (0-3.2) ng / mL, in 48 months - 0.9 (0.4-7.5) ng / mL. In 13 patients (27.7%) at 6 months was observed progression of the disease. In general, after a 5-year follow-up 72.3% of the patients had no data for the progression and recurrence. Conclusion: HIFU therapy in patients with local recurrence of prostate cancer after EBRT and RPE is minimally invasive and effective technology.

[Recto-vesico-cutaneous fistula following salvage cryotherapy of the prostate due to recurrent localized prostate cancer].

PubMed

Kocot, A; Spahn, M; Loeser, A; Riedmiller, H

2011-11-01

For patients with recurrent prostate cancer after initial external beam radiation salvage cryotherapy is considered as an alternative to salvage prostatectomy. We report a serious complication of salvage cryotherapy in a 72-year-old man suffering from a severe recto-vesico-cutaneous fistula 6 weeks after salvage cryotherapy. To manage this situation salvage cystoprostatectomy and continent urinary diversion with creation of an ileocaecal pouch with cutaneous stoma had to be performed.

Proteins Annexin A2 and PSA in Prostate Cancer Biopsies Do Not Predict Biochemical Failure.

PubMed

Lamb, David S; Sondhauss, Sven; Dunne, Jonathan C; Woods, Lisa; Delahunt, Brett; Ferguson, Peter; Murray, Judith; Nacey, John N; Denham, James W; Jordan, T William

2017-12-01

We previously reported the use of mass spectrometry and western blotting to identify proteins from tumour regions of formalin-fixed paraffin-embedded biopsies from 16 men who presented with apparently localized prostate cancer, and found that annexin A2 (ANXA2) appeared to be a better predictor of subsequent biochemical failure than prostate-specific antigen (PSA). In this follow-up study, ANXA2 and PSA were measured using western blotting of proteins extracted from biopsies from 37 men from a subsequent prostate cancer trial. No significant differences in ANXA2 and PSA levels were observed between men with and without biochemical failure. The statistical effect sizes were small, d=0.116 for ANXA2, and 0.266 for PSA. ANXA2 and PSA proteins measured from biopsy tumour regions are unlikely to be good biomarkers for prediction of the clinical outcome of prostate cancer presenting with apparently localized disease. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Prostate-specific antigen density is predictive of outcome in suboptimal prostate seed brachytherapy.

PubMed

Benzaquen, David; Delouya, Guila; Ménard, Cynthia; Barkati, Maroie; Taussky, Daniel

In prostate seed brachytherapy, a D 90 of <130 Gy is an accepted predictive factor for biochemical failure (BF). We studied whether there is a subpopulation that does not need additional treatment after a suboptimal permanent seed brachytherapy implantation. A total of 486 patients who had either BF or a minimum followup of 48 months without BF were identified. BF was defined according to the Phoenix definition (nadir prostate-specific antigen + 2). Univariate and multivariate analyses were performed, adjusting for known prognostic factors such as D 90 and prostate-specific antigen density (PSAD) of ≥0.15 ng/mL/cm 3 , to evaluate their ability to predict BF. Median followup for patients without BF was 72 months (interquartile range 56-96). BF-free recurrence rate at 5 years was 95% and at 8 years 88%. In univariate analysis, PSAD and cancer of the prostate risk assessment score were predictive of BF. On multivariate analysis, none of the factors remained significant. The best prognosis had patients with a low PSAD (<0.15 ng/mL/cm 3 ) and an optimal implant at 30 days after implantation (as defined by D 90  ≥ 130 Gy) compared to patients with both factors unfavorable (p = 0.006). A favorable PSAD was associate with a good prognosis, independently of the D 90 (<130 Gy vs. ≥130 Gy, p = 0.7). Patients with a PSAD of <0.15 ng/mL/cm 3 have little risk of BF, even in the case of a suboptimal implant. These results need to be validated in other patients' cohorts. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Paired high-content analysis of prostate cancer cells in bone marrow and blood characterizes increased androgen receptor expression in tumor cell clusters

PubMed Central

Carlsson, Anders; Kuhn, Peter; Luttgen, Madelyn S.; Dizon, Kevin K.; Troncoso, Patricia; Corn, Paul G.; Kolatkar, Anand; Hicks, James B.; Logothetis, Christopher J.; Zurita., Amado J.

2017-01-01

Purpose Recent studies demonstrate that prostate cancer clones from different metastatic sites are dynamically represented in the blood of patients over time, suggesting that the paired evaluation of tumor cells in circulation and bone marrow, the primary target for prostate cancer metastasis, may provide complementary information. Experimental Design We adapted our single-cell high-content liquid biopsy platform to bone marrow aspirates (BMA), to concurrently identify and characterize prostate cancer cells in patients’ blood and bone and thus discern features associated to tumorigenicity and dynamics of metastatic progression. Results The incidence of tumor cells in BMAs increased as the disease advanced: 0% in biochemically-recurrent (n=52), 26% in newly diagnosed metastatic hormone-naïve (n=26), and 39% in metastatic castration-resistant (mCRPC; n=63) patients, and their number was often higher than in paired blood. Tumor cell detection in metastatic patients’ BMAs was concordant but 45% more sensitive than using traditional histopathologic interpretation of core bone marrow biopsies. Tumor cell clusters were more prevalent and bigger in BMAs than in blood, expressed higher levels of the androgen receptor protein per tumor cell and were prognostic in mCRPC. Moreover, the patterns of genomic copy number variation in single tumor cells in paired blood and BMAs showed significant inter and intrapatient heterogeneity. Conclusions Paired analysis of single prostate cancer cells in blood and bone shows promise for clinical application and provides complementary information. The high prevalence and prognostic significance of tumor cell clusters particularly in BMAs, suggest that these structures are key mediators of prostate cancer’s metastatic progression. PMID:27702818

Robot-Assisted Radical Prostatectomy After Previous Prostate Surgery

PubMed Central

Tugcu, Volkan; Sahin, Selcuk; Kargi, Taner; Gokhan Seker, Kamil; IlkerComez, Yusuf; IhsanTasci, Ali

2015-01-01

Background and Objectives: Our objective is to clarify the effect of previous transurethral resection of the prostate (TURP) or open prostatectomy (OP) on surgical, oncological, and functional outcomes after robot-assisted radical prostatectomy (RARP). Methods: Between August 1, 2009, and March 31, 2013, 380 patients underwent RARP. Of these, 25 patients had undergone surgery for primary bladder outlet obstruction (TURP, 20 patients; OP, 5 patents) (group 1). A match-paired analysis was performed to identify 36 patients without a history of prostate surgery with equivalent clinicopathologic characteristics to serve as a control group (group 2). Patients followed up for 12 months were assessed. Results: Both groups were similar with respect to preoperative characteristics, as mean age, body mass index, median prostate-specific antigen, prostate volume, clinical stage, the biopsy Gleason score, D'Amico risk, the American Society of Anesthesiologists (ASA) classification score, the International Prostate Symptom Score, continence, and potency status. RARP resulted in longer console and anastomotic time, as well as higher blood loss compared with surgery-naive patients. We noted a greater rate of urinary leakage (pelvic drainage, >4 d) in group 1 (12% vs 2,8%). The anastomotic stricture rate was significantly higher in group 1 (16% vs 2.8%). No difference was found in the pathologic stage, positive surgical margin, and nerve-sparing procedure between the groups. Biochemical recurrence was observed in 12% (group 1) and 11.1% (group 2) of patients, respectively. No significant difference was found in the continence and potency rates. Conclusions: RARP after TURP or OP is a challenging but oncologically promising procedure with a longer console and anastomosis time, as well as higher blood loss and higher anastomotic stricture rate. PMID:26648678

Time from first detectable PSA following radical prostatectomy to biochemical recurrence: A competing risk analysis.

PubMed

de Boo, Leonora; Pintilie, Melania; Yip, Paul; Baniel, Jack; Fleshner, Neil; Margel, David

2015-01-01

In this study, we estimated the time from first detectable prostate-specific antigen (PSA) following radical prostatectomy (RP) to commonly used definitions of biochemical recurrence (BCR). We also identified the predictors of time to BCR. We identified subjects who underwent a RP and had an undetectable PSA after surgery followed by at least 1 detectable PSA between 2000 and 2011. The primary outcome was time to BCR (PSA ≥0.2 and successive PSA ≥0.2) and prediction of the rate of PSA rise. Outcomes were calculated using a competing risk analysis, with univariable and multivariable Fine and Grey models. We employed a mixed effect model to test clinical predictors that are associated with the rate of PSA rise. The cohort included 376 patients. The median follow-up from surgery was 60.5 months (interquartile range [IQR] 40.8-91.5) and from detectable PSA was 18 months (IQR 11-32). Only 45.74% (n = 172) had PSA values ≥0.2 ng/mL, while 15.16% (n = 57) reached the PSA level of ≥0.4 ng/mL and rising. On multivariable analysis, the values of the first detectable PSA and pathologic Gleason grade 8 or higher were consistently independent predictors of time to BCR. In the mixed effect model rate, the PSA rise was associated with time from surgery to first detectable PSA, Gleason score, and prostate volume. The main limitation of this study is the large proportion of patients that received treatment without reaching BCR. It is plausible that shorter estimated median times would occur at a centre that does not use salvage therapy at such an early state. The time from first detectable PSA to BCR may be lengthy. Our analyses of the predictors of the rate of PSA rise can help determine a personalized approach for patients with a detectable PSA after surgery.

Time from first detectable PSA following radical prostatectomy to biochemical recurrence: A competing risk analysis

PubMed Central

de Boo, Leonora; Pintilie, Melania; Yip, Paul; Baniel, Jack; Fleshner, Neil; Margel, David

2015-01-01

Introduction: In this study, we estimated the time from first detectable prostate-specific antigen (PSA) following radical prostatectomy (RP) to commonly used definitions of biochemical recurrence (BCR). We also identified the predictors of time to BCR. Methods: We identified subjects who underwent a RP and had an undetectable PSA after surgery followed by at least 1 detectable PSA between 2000 and 2011. The primary outcome was time to BCR (PSA ≥0.2 and successive PSA ≥0.2) and prediction of the rate of PSA rise. Outcomes were calculated using a competing risk analysis, with univariable and multivariable Fine and Grey models. We employed a mixed effect model to test clinical predictors that are associated with the rate of PSA rise. Results: The cohort included 376 patients. The median follow-up from surgery was 60.5 months (interquartile range [IQR] 40.8–91.5) and from detectable PSA was 18 months (IQR 11–32). Only 45.74% (n = 172) had PSA values ≥0.2 ng/mL, while 15.16% (n = 57) reached the PSA level of ≥0.4 ng/mL and rising. On multivariable analysis, the values of the first detectable PSA and pathologic Gleason grade 8 or higher were consistently independent predictors of time to BCR. In the mixed effect model rate, the PSA rise was associated with time from surgery to first detectable PSA, Gleason score, and prostate volume. The main limitation of this study is the large proportion of patients that received treatment without reaching BCR. It is plausible that shorter estimated median times would occur at a centre that does not use salvage therapy at such an early state. Conclusion: The time from first detectable PSA to BCR may be lengthy. Our analyses of the predictors of the rate of PSA rise can help determine a personalized approach for patients with a detectable PSA after surgery. PMID:25624961

Methylation of subtelomeric repeat D4Z4 in peripheral blood leukocytes is associated with biochemical recurrence in localized prostate cancer patients.

PubMed

Han, Yuyan; Xu, Junfeng; Kim, Jeri; Wu, Xifeng; Gu, Jian

2017-08-01

Global DNA methylation may affect chromosome structure and genomic stability and is involved in carcinogenesis. In this study, we aimed to investigate whether methylation of pericentromeric repeat NBL2 and subtelomeric repeat D4Z4 in peripheral blood was associated with the aggressiveness of prostate cancer (PCa). We measured the methylation status of different CpG sites of NBL2 and D4Z4 in 795 PCa patients and compared their methylation levels among patients with different Gleason Score at diagnosis. We then analyzed the association of the NBL2 and D4Z4 methylation with the risk of biochemical recurrence (BCR) in patients receiving radical prostatectomy or radiotherapy using a multivariate Cox proportional hazards model. In addition, we used the Kaplan-Meier survival function and log-rank tests to assess BCR-free survival associated with D4Z4 methylation. There was no significant difference in methylation level of NBL2 and D4Z4 between clinically defined aggressive and non-aggressive PCa at diagnosis. However, the methylation of D4Z4 was associated with BCR, while the methylation of NBL2 was not. In tertile analysis, patients in the highest tertile of D4Z4 methylation had an increased risk of BCR (HR = 2.17, 95% CI 1.36-3.48) compared to patients in the lower tertiles after adjustment of age, body mass index, smoking status, pack year, D'Amico risk groups and treatments. Among the four CpG sites in this region, the association was mostly attributable to the methylation of the second CpG site of D4Z4. These data suggest that higher methylation in D4Z4 was associated with worse prognosis of localized PCa patients. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Possible protective effect of royal jelly against cyclophosphamide induced prostatic damage in male albino rats; a biochemical, histological and immuno-histo-chemical study.

PubMed

Abdel-Hafez, Sara Mohammed Naguib; Rifaai, Rehab Ahmed; Abdelzaher, Walaa Yehia

2017-06-01

Almost all the chemotherapy treat many cancer types effectively, but it leads to severe side effects. Chemotherapy like cyclophosphamide (CP) not works only on the active cells, such as cancer cells, but also acts on the healthy cells. Royal jelly (RJ) was reported to have a lot of therapeutic effects besides being an anti-oxidant and anti-cancer agent. The purpose of this study was to assess the possible protective role of RJ in ameliorating the toxic effects of CP overdose in the rat prostatic tissue. The rats were separated into 4 groups; control group, RJ group, CP group and RJ with CP group. Prostatic specimens were processed for biochemical, histological and immune-histo-chemical studies. The mean area fractions of eNOS and Bax expression were measured in all groups, and statistical analysis was carried out. The results showed that in CP treated group, there were marked biological changes in the form of significant increase in prostatic malondialdehyde (MDA) and C - reactive protein (CRP). Additionally there was a significant decrease in glutathione peroxidase (GPx) in prostatic tissue if compared with the control group. Furthermore, the histological changes showed marked acinar and stromal prostatic degeneration. Most prostatic acini showed less PAS reaction and more (eNOS and Bax) expression if compared with the control group. Concomitant administration of RJ with CP revealed a noticeable amelioration of these biochemical and histological changes. In conclusion, RJ provided biochemical and histo-pathological improvement in CP induced prostatic tissue toxicity. These findings revealed that this improvement was associated with a decrease in the tissue oxidative damage and apoptosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Real-time individual predictions of prostate cancer recurrence using joint models

PubMed Central

Taylor, Jeremy M. G.; Park, Yongseok; Ankerst, Donna P.; Proust-Lima, Cecile; Williams, Scott; Kestin, Larry; Bae, Kyoungwha; Pickles, Tom; Sandler, Howard

2012-01-01

Summary Patients who were previously treated for prostate cancer with radiation therapy are monitored at regular intervals using a laboratory test called Prostate Specific Antigen (PSA). If the value of the PSA test starts to rise, this is an indication that the prostate cancer is more likely to recur, and the patient may wish to initiate new treatments. Such patients could be helped in making medical decisions by an accurate estimate of the probability of recurrence of the cancer in the next few years. In this paper, we describe the methodology for giving the probability of recurrence for a new patient, as implemented on a web-based calculator. The methods use a joint longitudinal survival model. The model is developed on a training dataset of 2,386 patients and tested on a dataset of 846 patients. Bayesian estimation methods are used with one Markov chain Monte Carlo (MCMC) algorithm developed for estimation of the parameters from the training dataset and a second quick MCMC developed for prediction of the risk of recurrence that uses the longitudinal PSA measures from a new patient. PMID:23379600

Salvage prostatectomy in patients who have failed radiation therapy or cryotherapy as primary treatment for prostate cancer.

PubMed

Chen, Bert T; Wood, David P

2003-12-29

Asymptomatic prostate-specific antigen (PSA) recurrence after radiation therapy for prostate carcinoma poses a diagnostic and therapeutic dilemma for clinicians. Patients with locally recurrent disease can consider treatment options of salvage surgery, cryotherapy, watchful waiting, or androgen deprivation. Of these options, only salvage surgery has been shown to result in long-term disease-free survival for selected patients. However, salvage surgery is associated with significant morbidity, including urinary incontinence and rectal injuries. Ideally, salvage surgery outcomes can be optimized with careful patient selection according to clinical stage, serum PSA levels before radiation and surgery, the medical condition of the patient, and clear expectations of the physician and patient. Among patients with locally recurrent disease, those with localized prostate carcinoma amenable to radical prostatectomy before radiation or cryotherapy would be the most suitable candidates for salvage surgery.

ADD-ASPIRIN: A phase III, double-blind, placebo controlled, randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common non-metastatic solid tumours.

PubMed

Coyle, Christopher; Cafferty, Fay H; Rowley, Samuel; MacKenzie, Mairead; Berkman, Lindy; Gupta, Sudeep; Pramesh, C S; Gilbert, Duncan; Kynaston, Howard; Cameron, David; Wilson, Richard H; Ring, Alistair; Langley, Ruth E

2016-11-01

There is a considerable body of pre-clinical, epidemiological and randomised data to support the hypothesis that aspirin has the potential to be an effective adjuvant cancer therapy. Add-Aspirin is a phase III, multi-centre, double-blind, placebo-controlled randomised trial with four parallel cohorts. Patients who have undergone potentially curative treatment for breast (n=3100), colorectal (n=2600), gastro-oesophageal (n=2100) or prostate cancer (n=2120) are registered into four tumour specific cohorts. All cohorts recruit in the United Kingdom, with the breast and gastro-oesophageal cohort also recruiting in India. Eligible participants first undertake an active run-in period where 100mg aspirin is taken daily for approximately eight weeks. Participants who are able to adhere and tolerate aspirin then undergo a double-blind randomisation and are allocated in a 1:1:1 ratio to either 100mg aspirin, 300mg aspirin or a matched placebo to be taken daily for at least five years. Those participants ≥75years old are only randomised to 100mg aspirin or placebo due to increased toxicity risk. The primary outcome measures are invasive disease-free survival for the breast cohort, disease-free survival for the colorectal cohort, overall survival for the gastro-oesophageal cohort, and biochemical recurrence-free survival for the prostate cohort, with a co-primary outcome of overall survival across all cohorts. Secondary outcomes include adherence, toxicity including serious haemorrhage, cardiovascular events and some cohort specific measures. The Add-Aspirin trial investigates whether regular aspirin use after standard therapy prevents recurrence and prolongs survival in participants with four non-metastatic common solid tumours. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Number of positive preoperative biopsy cores is a predictor of positive surgical margins (PSM) in small prostates after robot-assisted radical prostatectomy (RARP).

PubMed

Tuliao, Patrick H; Koo, Kyo C; Komninos, Christos; Chang, Chien H; Choi, Young D; Chung, Byung H; Hong, Sung J; Rha, Koon H

2015-12-01

To determine the impact of prostate size on positive surgical margin (PSM) rates after robot-assisted radical prostatectomy (RARP) and the preoperative factors associated with PSM. In all, 1229 men underwent RARP by a single surgeon, from 2005 to August of 2013. Excluded were patients who had transurethral resection of the prostate, neoadjuvant therapy, clinically advanced cancer, and the first 200 performed cases (to reduce the effect of learning curve). Included were 815 patients who were then divided into three prostate size groups: <31 g (group 1), 31-45 g (group 2), >45 g (group 3). Multivariate analysis determined predictors of PSM and biochemical recurrence (BCR). Console time and blood loss increased with increasing prostate size. There were more high-grade tumours in group 1 (group 1 vs group 2 and group 3, 33.9% vs 25.1% and 25.6%, P = 0.003 and P = 0.005). PSM rates were higher in prostates of <45 g with preoperative PSA levels of >20 ng/dL, Gleason score ≥7, T3 tumour, and ≥3 positive biopsy cores. In group 1, preoperative stage T3 [odds ratio (OR) 3.94, P = 0.020] and ≥3 positive biopsy cores (OR 2.52, P = 0.043) were predictive of PSM, while a PSA level of >20 ng/dL predicted the occurrence of BCR (OR 5.34, P = 0.021). No preoperative factors predicted PSM or BCR for groups 2 and 3. A preoperative biopsy with ≥3 positive cores in men with small prostates predicts PSM after RARP. In small prostates with PSM, a PSA level of >20 ng/dL is a predictor of BCR. These factors should guide the choice of therapy and indicate the need for closer postoperative follow-up. © 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.

Importance of 5α-reductase gene polymorphisms on circulating and intraprostatic androgens in prostate cancer.

PubMed

Lévesque, Éric; Laverdière, Isabelle; Lacombe, Louis; Caron, Patrick; Rouleau, Mélanie; Turcotte, Véronique; Têtu, Bernard; Fradet, Yves; Guillemette, Chantal

2014-02-01

Polymorphisms in the genes SRD5A1 and SRD5A2 encoding androgen biosynthetic 5α-reductase enzymes have been associated with an altered risk of biochemical recurrence after radical prostatectomy in localized prostate cancer. To gain potential insights into SRD5A biologic effects, we examined the relationship between SRD5A prognostic markers and endogenous sex-steroid levels measured by mass spectrometry in plasma samples and corresponding prostatic tissues of patients with prostate cancer. We report that five of the seven SRD5A markers differentially affect sex-steroid profiles of dihydrotestosterone and its metabolites in both the circulation and prostatic tissues of patients with prostate cancer. Remarkably, a 32% increase in intraprostatic testosterone levels was observed in the presence of the high-risk SRD5A rs2208532 polymorphism. Moreover, SRD5A2 markers were associated predominantly with circulating levels of inactive glucuronides. Indeed, the rs12470143 SRD5A2 protective allele was associated with high circulating androstane-3α, 17β-diol-17-glucuronide (3α-diol-17G) levels as opposed to lower levels of both 3α-diol-17G and androsterone-glucuronide observed with the rs2208532 SRD5A2 risk allele. Moreover, SRD5A2 rs676033 and rs523349 (V89L) risk variants, in strong linkage disequilibrium, were associated with higher circulating levels of 3α-diol-3G. The SRD5A2 rs676033 variant further correlated with enhanced intraprostatic exposure to 5α-reduced steroids (dihydrotestosterone and its metabolite 3β-diol). Similarly, the SRD5A1 rs166050C risk variant was associated with greater prostatic exposure to androsterone, whereas no association was noted with circulating steroids. Our data support the association of 5α-reductase germline polymorphisms with the hormonal milieu in patients with prostate cancer. Further studies are needed to evaluate if these variants influence 5α-reductase inhibitor efficacy. ©2013 AACR.

sEphB4-HSA Before Surgery in Treating Patients With Bladder Cancer, Prostate Cancer, or Kidney Cancer

ClinicalTrials.gov

2018-06-08

Infiltrating Bladder Urothelial Carcinoma; Recurrent Bladder Carcinoma; Stage I Prostate Cancer; Stage I Renal Cell Cancer; Stage II Bladder Urothelial Carcinoma; Stage II Renal Cell Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage III Renal Cell Cancer

Effect of family history on outcomes in patients treated with definitive brachytherapy for clinically localized prostate cancer.

PubMed

Peters, Christopher A; Stock, Richard G; Blacksburg, Seth R; Stone, Nelson N

2009-01-01

To determine the impact familial prostate cancer has on prognosis in men treated with brachytherapy for clinically localized prostate cancer. A total of 1,738 consecutive patients with prostate cancer (cT1-3, N0/X, M0) received low-dose-rate brachytherapy alone or in combination with external beam radiation therapy or hormone ablation from 1992 to 2005. The primary end-point was freedom from biochemical failure (FFBF) using the Phoenix definition. Minimum follow-up was 2 years and the median follow-up was 60 months (range, 24-197 months). A total of 187 of 1,738 men (11%) had a family history of prostate cancer in a first-degree relative. For the low-risk patients, both groups had similar actuarial 5-year FFBF (97.2% vs. 95.5%, p = 0.516). For intermediate-risk patients, there was a trend toward improved biochemical control in men positive for family history (5-yr FFBF 100% vs. 93.6%, p = 0.076). For the high-risk patients, men with a positive family history had similar 5-year FFBF (92.8% vs. 85.2%, p = 0.124). On multivariate analysis, family history was not significant; use of hormones, high biologic effective dose, initial prostate-specific antigen value, and Gleason score were the significant variables predicting biochemical control. This is the first study to examine the relationship of familial prostate cancer and outcomed in men treated with brachytherapy alone or in combination therapy. Men with a positive family history have clinicopathologic characteristics and biochemical outcomes similar to those with sporadic disease.

68Ga-PSMA-11 PET/CT-derived metabolic parameters for determination of whole-body tumor burden and treatment response in prostate cancer.

PubMed

Schmidkonz, Christian; Cordes, Michael; Schmidt, Daniela; Bäuerle, Tobias; Goetz, Theresa Ida; Beck, Michael; Prante, Olaf; Cavallaro, Alexander; Uder, Michael; Wullich, Bernd; Goebell, Peter; Kuwert, Torsten; Ritt, Philipp

2018-05-03

We aimed at evaluating the role of 68 Ga-PSMA-11 PET/CT-derived metabolic parameters for assessment of whole-body tumor burden and its capability to determine therapeutic response in patients with prostate cancer. A total of 142 patients with biochemical recurrence of prostate cancer underwent PET/CT with [ 68 Ga]Ga-PSMA-HBED-CC ( 68 Ga-PSMA-11). Quantitative assessment of all 641 68 Ga-PSMA-11-positive lesions in the field of view was performed to calculate PSMA-derived parameters, including whole-body PSMA tumor volume (PSMA-TV) and whole-body total lesion PSMA (TL-PSMA), as well as the established SUVmax and SUVmean values. All PET-derived parameters were tested for correlation with serum PSA levels and for association with Gleason scores. In 23 patients who underwent 68 Ga-PSMA-11 PET/CT before and after therapy with either external beam radiation, androgen deprivation, or docetaxel chemotherapy, SUVmax and TL-PSMA were compared to radiographic response assessment of CT images based on RECIST 1.1 criteria and to biochemical response determined by changes of serum PSA levels. PSMA-TV and TL-PSMA demonstrated a significant correlation with serum PSA levels (P < 0.0001) and TL-PSMA was significantly different for different Gleason scores. The agreement rate between TL-PSMA derived from PET and biochemical response was 87% (95% confidence interval, 0.66-0.97; Cohen's κ = 0.78; P < 0.01) and, thus, higher than for SUVmax, which was 74% (95% CI, 0.52-0.90; κ = 0.55; P < 0.01). Furthermore, agreement with PSA was higher for TL-PSMA and SUVmax than for CT-based response evaluation. Discordant findings between PET and CT were most likely due to limitations of CT and RECIST in rating small lymph nodes as metastases, as well as bone involvement, which was sometimes not detectable in CT. 68 Ga-PSMA-11 PET/CT-derived metabolic tumor parameters showed promising results for evaluation of treatment response. Especially, TL-PSMA demonstrated higher agreement rates with biochemical response compared to SUVmax. Larger, ideally prospective trials are needed to help to reveal the full potential of metabolic parameters derived from PET imaging with 68 Ga-PSMA-11.

MicroRNA-126 inhibits proliferation and metastasis in prostate cancer via regulation of ADAM9

PubMed Central

Hua, Yibo; Liang, Chao; Miao, Chenkui; Wang, Shangqian; Su, Shifeng; Shao, Pengfei; Liu, Bianjiang; Bao, Meiling; Zhu, Jundong; Xu, Aiming; Zhang, Jianzhong; Li, Jie; Wang, Zengjun

2018-01-01

The aberrant expression of microRNAs (miRs) has been identified to serve a crucial role in tumor progression. The present study aimed to evaluate the role of miR-126 in human prostate cancer (PCa). Firstly, miR-126 expression in prostate cancer tissues and cell lines was analyzed. A luciferase reporter assay and a rescue assay were performed, which identified ADAM metalloproteinase domain 9 (ADAM9) as the target gene of miR-126. Subsequently, Kaplan-Meier and log-rank analyses were used to investigate the association between ADAM9 expression and PCa prognosis. The results revealed that miR-126 expression was significantly downregulated in PCa tissues and cell lines. miR-126 overexpression was demonstrated to reduce PCa cell proliferation and metastasis, and to reverse the epithelial-mesenchymal transition process in vitro. In addition, as the target gene of miR-126, the upregulation of ADAM9 reestablished cell functions, including cell proliferation, migration and invasion. Patients with high ADAM9 expression levels exhibited a shorter biochemical recurrence-free survival time. In summary, miR-126 serves a role in the proliferation and metastasis of PCa cells, indicating that miR-126 and ADAM9 may represent potential biomarkers in the progression of advanced PCa, in addition to therapeutic targets. PMID:29805636

Young Men Have Equivalent Biochemical Outcomes Compared With Older Men After Treatment With Brachytherapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burri, Ryan J.; Ho, Alice Y.; Forsythe, Kevin

Purpose: To evaluate retrospectively the biochemical outcomes of young men treated with low-dose-rate brachytherapy for prostate cancer. Methods and Materials: From 1990 to 2005, 1,665 men with clinically localized prostate cancer were treated with low-dose-rate brachytherapy {+-} hormone therapy (HT) {+-} external beam radiotherapy and underwent {>=}2 years of follow-up. Patients were stratified on the basis of age: {<=}60 (n = 378) and >60 years (n = 1,287). Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/mL. Univariate and multivariate analyses were used to determine the association of variables with freedom from biochemical failure (FFbF). Results:more » Median follow-up was 68 months (range, 24-180) for men {<=}60 years and 66 months (range, 24-200) for men >60. For the entire group, the actuarial 5- and 8-year FFbF rates were 94% and 88%, respectively. Men {<=}60 demonstrated similar 5- and 8-year FFbF (95% and 92%) compared with men >60 (93% and 87%; p = 0.071). A larger percent of young patients presented with low-risk disease; lower clinical stage, Gleason score (GS), and pretreatment PSA values; were treated after 1997; did not receive any HT; and had a high biologic effective dose (BED) of radiation (all ps <0.001). On multivariate analysis, PSA (p = 0.001), GS (p = 0.005), and BED (p < 0.001) were significantly associated with FFbF, but age was not (p = 0.665). Conclusion: Young men achieve excellent 5- and 8-year biochemical control rates that are comparable to those of older men after prostate brachytherapy. Young age should not be a deterrent when considering brachytherapy as a primary treatment option for clinically localized prostate cancer.« less

Clinical Profile, Quality of Care, and Recurrence in Arab-American and Caucasians Prostate Cancer Patients in Michigan

PubMed Central

Moussawi, Ahmad H.; Yassine, May; Dey, Subhojit

2014-01-01

Prostate cancer is the most common cancer among men in the United States with striking differences in incidence and mortality among ethnic groups. Michigan has one of the largest concentrations of Arab Americans (AAs) in the U.S. and little is known about this ethnic minority with respect to prostate cancer. This study investigated differences in clinical profile, quality of care, and recurrence among prostate cancer survivors comparing AAs and Caucasian Americans (CAs). Participants in this study included 2499 prostate cancer survivors from the Michigan Cancer Registry from 1985 to 2004. Participants completed surveys regarding health-seeking behavior, post-treatment symptoms, quality of care and recurrence. Ethnicity was self-reported and AAs and CAs were compared with respect to clinical profile, quality of care, and recurrence. There were 52 AAs and 1886 CAs patients with AAs being younger (x̄ age 68.3 ± SD 21.4 years, x̄ age 72.3 ± SD 14.1 years, for AAs and CAs, respectively) (P = 0.05). AAs had lower socioeconomic standard than CAs (34 vs. 10.6 %, <$20,000 yearly income/year; for AAs vs. CAs, respectively) (P < 0.0001). AAs reported poorer health than AAs (7.7 vs. 3.0 % for AAs vs. CAs, respectively) (P < 0.0001). AAs were more likely to visit specialists for prostate follow-up (44.5 vs. 19.7 % visited a specialist, for AAs vs. CAs respectively) (P < 0.0001) and received supplementary healthcare workers (13 % of AAs vs. 3.1 % CAs) (P = 0.032). In addition, AAs reported higher occurrence of urinary incontinence compared to CAs (67.4 vs. 60.4 %, for AAs vs. CAs, respectively) (P = 0.001). Ethnic background was not a predictor of recurrence [(Odds ratio (OR) = 1.1 (95 % confidence intervals CI = 0.40, 2.9)] (P = 0.873) even after adjusting for age, PSA levels within the last 2 years, metastasis and hormonal therapy. While AAs prostate cancer patients were different from CAs in age, income, seeking medical care, and health reporting, ethnic background was not a predictor of recurrence. Future studies of the impact of socioeconomic, demographic and cultural factors, and health care seeking behavior on long-term survival of prostate cancer in AAs and other ethnic minorities are warranted. PMID:22763459

[Biochemical failure after curative treatment for localized prostate cancer].

PubMed

Zouhair, Abderrahim; Jichlinski, Patrice; Mirimanoff, René-Olivier

2005-12-07

Biochemical failure after curative treatment for localized prostate cancer is frequent. The diagnosis of biochemical failure is clear when PSA levels rise after radical prostatectomy, but may be more difficult after external beam radiation therapy. The main difficulty once biochemical failure is diagnosed is to distinguish between local and distant failure, given the low sensitivity of standard work-up exams. Metabolic imaging techniques currently under evaluation may in the future help us to localize the site of failures. There are several therapeutic options depending on the initial curative treatment, each with morbidity risks that should be considered in multidisciplinary decision-making.

Significance and outcome of nuclear anaplasia and mitotic index in prostatic adenocarcinomas.

PubMed

Kır, Gozde; Sarbay, Billur Cosan; Gumus, Eyup

2016-10-01

The Gleason grading system measures architectural differentiation and disregards nuclear atypia and the cell proliferation index. Several studies have reported that nuclear grade and mitotic index (MI) are prognostically useful. This study included 232 radical prostatectomy specimens. Nuclear anaplasia (NA) was determined on the basis of nucleomegali (at least 20µm); vesicular chromatin; eosinophilic macronucleoli, nuclear lobulation, and irregular thickened nuclear membranei. The proportion of area of NA was recorded in each tumor in 10% increments. The MI was defined as the number of mitotic figures in 10 consecutive high-power fields (HPF). In univariate analysis, significant differences included associations between biochemical prostate-specific antigen recurrence (BCR) and Gleason score, extraprostatic extension, positive surgical margin, the presence of high-pathologic stage, NA≥10% of tumor area, MI≥3/10 HPF, and preoperative prostate-specific antigen. In a stepwise Cox regression model, a positive surgical margin, the presence of a NA≥10% of tumor area, and a MI of≥3/10 HPF were independent predictors of BCR after radical prostatectomy. NA≥10% of tumor area appeared to have a stronger association with outcome than MI≥3/10 HPF, as still associated with BCR when Gleason score was in the model. The results of our study showed that, in addition to the conventional Gleason grading system, NA, and MI are useful prognostic parameters while evaluating long-term prognosis in prostatic adenocarcinoma. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of 68Ga-PSMA PET on the Management of Patients with Prostate Cancer: A Systematic Review and Meta-analysis.

PubMed

Han, Sangwon; Woo, Sungmin; Kim, Yeon Joo; Suh, Chong Hyun

2018-04-18

68 Gallium prostate-specific membrane antigen positron emission tomography ( 68 Ga-PSMA PET) is an emerging imaging modality for assessment of prostate cancer. Recent studies show promising results regarding its ability to detect recurrent or metastatic prostate cancer superior to that of conventional imaging modalities. However, the impact of 68 Ga-PSMA PET on management of patients with prostate cancer has not been well established. To perform a systematic review and meta-analysis to evaluate the impact of 68 Ga-PSMA PET on management of patients with prostate cancer. Pubmed and EMBASE databases were searched up to January 20, 2018. We included studies that reported proportion of management change after 68 Ga-PSMA PET in patients with prostate cancer. The quality of the studies was evaluated using the GRADE system. The proportion of management changes were pooled using random-effects model. Subgroup analyses and meta-regression analyses were performed to explore heterogeneity. Fifteen studies (1163 patients) were included. The pooled proportion of management changes was 54% (95% confidence interval 47-60%). At meta-regression analyses, PET positivity (%) was a significant factor of heterogeneity (p=0.0486). For patients with biochemical failure, the proportion of radiotherapy (from 56% to 61%), surgery (from 1% to 7%), focal therapy (from 1% to 2%), and multimodal treatment (from 2% to 6%) increased, whereas that of systemic treatment (from 26% to 12%) and no treatment (from 14% to 11%) decreased with 68 Ga-PSMA PET. 68 Ga-PSMA PET had a large impact on the management of patients with prostate cancer. Greater PET positivity was associated with higher proportion of management changes. We reviewed all previous studies assessing the impact of 68 Gallium prostate-specific membrane antigen positron emission tomography ( 68 Ga-PSMA PET) in patients with prostate cancer. We found that 68 Ga-PSMA PET altered the management in approximately half of the patients. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Late-onset granulomatous prostatitis following intravesical bacille Calmette-Guerin therapy: case report.

PubMed

Castillo Cádiz, Octavio; Villasenín Parrado, Lorena; Borgna Christie, Vincenzo; Gallegos Méndez, Iván; Martínez Corta, Virginia

2016-06-20

Bacille Calmette-Guerin intravesical treatment is the most effective treatment for reducing the recurrence of non-muscle-invasive urothelial carcinomas. This treatment can sometimes have side effects and serious complications. Granulomatous prostatitis is a common histological finding but it rarely has a clinical presentation. We report a case of a 75-year-old, type 2 diabetic, male patient who was diagnosed with urothelial in situ carcinoma, for which he began treatment with Bacille Calmette-Guerin instillations. Five years later the patient presented nocturia, pollakiuria, severe urgency, and intense and recurrent perineal pain associated with marked elevation of prostatic specific antigen. A prostatic biopsy was performed that showed a moderate to severe granulomatous prostatitis related to bacille Calmette-Guerin. The patient received full antituberculosis combination drugs with a favorable clinical response.

[Recurrent urological cancer--diagnose and treatment].

PubMed

Takeshima, H; Akaza, H

1998-02-01

Clinical efforts to spare bladder function even in the case of muscle invasive recurrent bladder cancer is taking. Early detection of recurrence is essential for bladder sparing, and both urinary NMP22 and BTA are thought to have potency to detect recurrence of bladder cancer earlier than urinary cytology. Intravesical administration of BCG for superficial bladder cancer and intraarterial injection of chemoagents (Methotrexate and Cisplatin) with radiation for muscle invasive bladder cancer are thought to play important roles in sparing the bladder. Early detection of recurrent prostate cancer is becoming easier by ultrasensitive PSA assay. Though the value of early detection of recurrence is not proven since the benefits of early hormonal treatment have not yet been established, that should be a good indicator to evaluate new and coming treatments and play a important role to develop an effective treatment for recurrent prostate cancer.

Uptake of 18F-DCFPyL in Paget's Disease of Bone, an Important Potential Pitfall in Clinical Interpretation of PSMA PET Studies.

PubMed

Rowe, Steven P; Deville, Curtiland; Paller, Channing; Cho, Steve Y; Fishman, Elliot K; Pomper, Martin G; Ross, Ashley E; Gorin, Michael A

2015-12-01

Prostate-specific membrane antigen (PSMA)-targeted PET imaging is an emerging technique for evaluating patients with prostate cancer (PCa) in a variety of clinical contexts. As with any new imaging modality, there are interpretive pitfalls that are beginning to be recognized. In this image report, we describe the findings in a 63-year-old male with biochemically recurrent PCa after radical prostatectomy who was imaged with 18 F-DCFPyL, a small molecule inhibitor of PSMA. Diffuse radiotracer uptake was noted throughout the sacrum, corresponding to imaging findings on contrast-enhanced CT, bone scan, and pelvic MRI consistent with Paget's disease of bone. The uptake of 18 F-DCFPyL in Paget's disease is most likely due to hyperemia and increased radiotracer delivery. In light of the overlap in patients affected by PCa and Paget's, it is important for nuclear medicine physicians and radiologists interpreting PSMA PET/CT scans to be aware of the potential for this diagnostic pitfall. Correlation to findings on conventional imaging such as diagnostic CT and bone scan can help confirm the diagnosis.

Prostate-Specific Antigen and Prostate-Specific Antigen Velocity as Threshold Indicators in 11C-Acetate PET/CTAC Scanning for Prostate Cancer Recurrence

PubMed Central

Dusing, Reginald W.; Peng, Warner; Lai, Sue-Min; Grado, Gordon L.; Holzbeierlein, Jeffrey M.; Thrasher, J. Brantley; Hill, Jacqueline; Van Veldhuizen, Peter J.

2014-01-01

Purpose The aim of this study was to identify which patient characteristics are associated with the highest likelihood of positive findings on 11C-acetate PET/computed tomography attenuation correction (CTAC) (PET/CTAC) scan when imaging for recurrent prostate cancer. Methods From 2007 to 2011, 250 11C-acetate PET/CTAC scans were performed at a single institution on patients with prostate cancer recurrence after surgery, brachytherapy, or external beam radiation. Of these patients, 120 met our inclusion criteria. Logistic regression analysis was used to examine the relationship between predictability of positive findings and patients’ characteristics, such as prostate-specific antigen (PSA) level at the time of scan, PSA kinetics, Gleason score, staging, and type of treatment before scan. Results In total, 68.3% of the 120 11C-acetate PET/CTAC scans were positive. The percentage of positive scans and PSA at the time of scanning and PSA velocity (PSAV) had positive correlations. The putative sensitivity and specificity were 86.6% and 65.8%, respectively, when a PSA level greater than 1.24 ng/mL was used as the threshold for scanning. The putative sensitivity and specificity were 74% and 75%, respectively, when a PSAV level greater than 1.32 ng/mL/y was used as the threshold. No significant associations were found between scan positivity and age, PSA doubling time, Gleason score, staging, or type of treatment before scanning. Conclusions This retrospective study suggests that threshold models of PSA greater than 1.24 ng/mL or PSAV greater than 1.32 ng/mL per year are independent predictors of positive findings in 11C-acetate PET/CTAC imaging of recurrent prostate cancer. PMID:25036021

Salvage therapy for locally recurrent prostate cancer after radiation.

PubMed

Marcus, David M; Canter, Daniel J; Jani, Ashesh B; Dobbs, Ryan W; Schuster, David M; Carthon, Bradley C; Rossi, Peter J

2012-12-01

External beam radiotherapy (EBRT) is widely utilized as primary therapy for clinically localized prostate cancer. For patients who develop locally recurrent disease after EBRT, local salvage therapy may be indicated. The primary modalities for local salvage treatment in this setting include radical prostatectomy, cryotherapy, and brachytherapy. To date, there is little data describing outcomes and toxicity associated with each of these salvage modalities. A review of the literature was performed to identify studies of local salvage therapy for patients who had failed primary EBRT for localized prostate cancer. We focused on prospective trials and multi-institutional retrospective series in order to identify the highest level of evidence describing these therapies. The majority of reports describing the use of local salvage treatment for recurrent prostate cancer after EBRT are single-institution, retrospective reports, although small prospective studies are available for salvage cryotherapy and salvage brachytherapy. Clinical outcomes and toxicity for each modality vary widely across studies, which is likely due to the heterogeneity of patient populations, treatment techniques, and definitions of failure. In general, most studies demonstrate that local salvage therapy after EBRT may provide long-term local control in appropriately selected patients, although toxicity is often significant. As there are no randomized trials comparing salvage treatment modalities for localized prostate cancer recurrence after EBRT, the selection of a local treatment modality should be made on a patient-by-patient basis, with careful consideration of each patient's disease characteristics and tolerance for the risks of treatment. Additional data, ideally from prospective randomized trials, is needed to guide decision making for patients with local recurrence after EBRT failure.

Romidepsin in Treating Patients With Lymphoma, Chronic Lymphocytic Leukemia, or Solid Tumors With Liver Dysfunction

ClinicalTrials.gov

2018-04-02

Glioma; Lymphoma; Metastatic Malignant Solid Neoplasm; Neuroendocrine Neoplasm; Recurrent Adult Soft Tissue Sarcoma; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Colorectal Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Lung Carcinoma; Recurrent Malignant Solid Neoplasm; Recurrent Melanoma; Recurrent Pancreatic Carcinoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Thyroid Gland Carcinoma; Refractory Chronic Lymphocytic Leukemia; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage III Breast Cancer AJCC v7; Stage III Colorectal Cancer AJCC v7; Stage III Cutaneous Melanoma AJCC v7; Stage III Lung Cancer AJCC v7; Stage III Pancreatic Cancer AJCC v6 and v7; Stage III Prostate Cancer AJCC v7; Stage III Renal Cell Cancer AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Breast Cancer AJCC v6 and v7; Stage IV Colorectal Cancer AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Lung Cancer AJCC v7; Stage IV Pancreatic Cancer AJCC v6 and v7; Stage IV Prostate Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7; Unresectable Solid Neoplasm

[Radiotherapy with androgen deprivation in high-risk prostate cancer: what outcomes on a Caribbean population?].

PubMed

Foahom Kamwa, A D; Vian, E; Agoua, G; Sénéchal, C; Bentaleb, Y; Fofana, M; Manip-M'ebobisse, N; Blanchet, P

2012-11-01

To analyze in a Caribbean population at 90% of African descent, the results of radiotherapy with androgen deprivation (AD) in high-risk prostate cancer (PCa). Fifty-nine consecutive patients with a high-risk PCa as defined by the D'AMICO classification and treated by radiotherapy with AD between January 2003 and April 2009 in our center were analyzed. The median dose of radiation and the median duration of AD were 70Gy and 37months respectively. Biochemical recurrence (BF), as primary outcome was defined according to the PHOENIX criteria (nadir PSA+2ng/mL). Multivariate analysis was performed to identify predictive factors of BF. The median follow-up was 47months. Eight (13.6%) patients had BF and four (6.8%) developed metastases. Six (10.2%) died during the follow-up. The 5years acturial biochemical disease-free survival was 79.7%. Multivariate analyses have shown that Gleason sum (GS) superior to 7 (P=0.029), AD duration less than 24months (P=0.004) and the rate of Nadir PSA greater or equal to 0.5ng/mL (P=0.011) were independent predictive factors of BF. This study was the first to our knowledge, to provide that radiotherapy associate with AD for HRPC among Caribbean men is effective as observed in other populations. Patients with GS superior to 7 could be considered for more aggressive treatments in clinical trials. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Vitamin D deficiency and insufficiency among patients with prostate cancer

PubMed Central

Trump, Donald L.; Chadha, Manpreet K.; Sunga, Annette Y.; Fakih, Marwan G.; Ashraf, Umeer; Silliman, Carrie G.; Hollis, Bruce W.; Nesline, Mary K.; Tian, Lili; Tan, Wei; Johnson, Candace S.

2009-01-01

Objective To assess the frequency of vitamin D deficiency among men with prostate cancer, as considerable epidemiological, in vitro, in vivo and clinical data support an association between vitamin D deficiency and prostate cancer outcome. Patients, subjects and methods The study included 120 ambulatory men with recurrent prostate cancer and 50 with clinically localized prostate cancer who were evaluated and serum samples assayed for 25-OH vitamin D levels. Then 100 controls (both sexes), matched for age and season of serum sample, were chosen from a prospective serum banking protocol. The relationship between age, body mass index, disease stage, Eastern Cooperative Oncology Group performance status, season and previous therapy on vitamin D status were evaluated using univariate and multivariate analyses. Results The mean 25-OH vitamin D level was 25.9 ng/mL in those with recurrent disease, 27.5 ng/mL in men with clinically localized prostate cancer and 24.5 ng/mL in controls. The frequency of vitamin D deficiency (< 20 ng/mL) and insufficiency (20–31 ng/mL) was 40% and 32% in men with recurrent prostate; 28% had vitamin D levels that were normal (32–100 ng/mL). Among men with localized prostate cancer, 18% were deficient, 50% were insufficient and 32% were normal. Among controls, 31% were deficient, 40% were insufficient and 29% were normal. Metastatic disease (P = 0.005) and season of blood sampling (winter/spring; P = 0.01) were associated with vitamin D deficiency in patients with prostate cancer, while age, race, performance status and body mass index were not. Conclusions Vitamin D deficiency and insufficiency were common among men with prostate cancer and apparently normal controls in the western New York region. PMID:19426195

Vitamin D deficiency and insufficiency among patients with prostate cancer.

PubMed

Trump, Donald L; Chadha, Manpreet K; Sunga, Annette Y; Fakih, Marwan G; Ashraf, Umeer; Silliman, Carrie G; Hollis, Bruce W; Nesline, Mary K; Tian, Lili; Tan, Wei; Johnson, Candace S

2009-10-01

To assess the frequency of vitamin D deficiency among men with prostate cancer, as considerable epidemiological, in vitro, in vivo and clinical data support an association between vitamin D deficiency and prostate cancer outcome. The study included 120 ambulatory men with recurrent prostate cancer and 50 with clinically localized prostate cancer who were evaluated and serum samples assayed for 25-OH vitamin D levels. Then 100 controls (both sexes), matched for age and season of serum sample, were chosen from a prospective serum banking protocol. The relationship between age, body mass index, disease stage, Eastern Cooperative Oncology Group performance status, season and previous therapy on vitamin D status were evaluated using univariate and multivariate analyses. The mean 25-OH vitamin D level was 25.9 ng/mL in those with recurrent disease, 27.5 ng/mL in men with clinically localized prostate cancer and 24.5 ng/mL in controls. The frequency of vitamin D deficiency (<20 ng/mL) and insufficiency (20-31 ng/mL) was 40% and 32% in men with recurrent prostate; 28% had vitamin D levels that were normal (32-100 ng/mL). Among men with localized prostate cancer, 18% were deficient, 50% were insufficient and 32% were normal. Among controls, 31% were deficient, 40% were insufficient and 29% were normal. Metastatic disease (P = 0.005) and season of blood sampling (winter/spring; P = 0.01) were associated with vitamin D deficiency in patients with prostate cancer, while age, race, performance status and body mass index were not. Vitamin D deficiency and insufficiency were common among men with prostate cancer and apparently normal controls in the western New York region.

Very Early Salvage Radiotherapy Improves Distant Metastasis-Free Survival.

PubMed

Abugharib, Ahmed; Jackson, William C; Tumati, Vasu; Dess, Robert T; Lee, Jae Y; Zhao, Shuang G; Soliman, Moaaz; Zumsteg, Zachary S; Mehra, Rohit; Feng, Felix Y; Morgan, Todd M; Desai, Neil; Spratt, Daniel E

2017-03-01

Early salvage radiotherapy following radical prostatectomy for prostate cancer is commonly advocated in place of adjuvant radiotherapy. We aimed to determine the optimal definition of early salvage radiotherapy. We performed a multi-institutional retrospective study of 657 men who underwent salvage radiotherapy between 1986 and 2013. Two comparisons were made to determine the optimal definition of early salvage radiotherapy, including 1) the time from radical prostatectomy to salvage radiotherapy (less than 9, 9 to 21, 22 to 47 or greater than 48 months) and 2) the level of detectable pre-salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 or greater than 0.5 ng/ml). Outcomes included freedom from salvage androgen deprivation therapy, and biochemical relapse-free, distant metastases-free and prostate cancer specific survival. Median followup was 9.8 years. Time from radical prostatectomy to salvage radiotherapy did not correlate with 10-year biochemical relapse-free survival rates (R 2 = 0.18). Increasing pre-salvage radiotherapy prostate specific antigen strongly correlated with biochemical relapse-free survival (R 2 = 0.91). Increasing detectable pre-salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 and greater than 0.5 ng/ml) predicted worse 10-year biochemical relapse-free survival (62%, 44% and 27%), freedom from salvage androgen deprivation therapy (77%, 66% and 49%), distant metastases-free survival (86%, 79% and 66%, each p <0.001) and prostate cancer specific survival (93%, 89% and 80%, respectively, p = 0.001). On multivariable analysis early salvage radiotherapy (prostate specific antigen greater than 0.2 to 0.5 ng/ml) was associated with a twofold increase in biochemical failure, use of salvage androgen deprivation therapy and distant metastases compared to very early salvage radiotherapy (prostate specific antigen 0.01 to 0.2 ng/ml). The duration from radical prostatectomy to salvage radiotherapy is not independently prognostic for outcomes after salvage radiotherapy and it should not be used to define early salvage radiotherapy. Grouping all patients with pre-salvage radiotherapy prostate specific antigen 0.5 ng/ml or less may be inadequate to define early salvage radiotherapy and it has a relevant impact on ongoing and future clinical trials. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Combination Therapy Improves Survival in Prostate Cancer Model | Center for Cancer Research

Cancer.gov

Surgery and radiotherapy are the recommended treatments for localized prostate cancer. Recurrent prostate cancer, however, is often treated with androgen-deprivation therapy. Most patients who undergo this type of therapy eventually develop castration-resistant prostate cancer (CRPC). Though initially androgen-related therapies for CRPC had been thought to be ineffective,

78 FR 24750 - Scientific Information Request Therapies for Clinically Localized Prostate Cancer

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-26

... and benefits of the following therapies for clinically localized prostate cancer? a. Radical... prostate cancer: radical prostatectomy (including retropubic, perineal, laparoscopic, robotic-assisted..., biochemical (PSA) progression, metastatic and/or clinical progression-free survival, health status, and...

Validation of the 2015 prostate cancer grade groups for predicting long-term oncologic outcomes in a shared equal-access health system.

PubMed

Schulman, Ariel A; Howard, Lauren E; Tay, Kae Jack; Tsivian, Efrat; Sze, Christina; Amling, Christopher L; Aronson, William J; Cooperberg, Matthew R; Kane, Christopher J; Terris, Martha K; Freedland, Stephen J; Polascik, Thomas J

2017-11-01

A 5-tier prognostic grade group (GG) system was enacted to simplify the risk stratification of patients with prostate cancer in which Gleason scores of ≤6, 3 + 4, 4 + 3, 8, and 9 or 10 are considered GG 1 through 5, respectively. The authors investigated the utility of biopsy GG for predicting long-term oncologic outcomes after radical prostatectomy in an equal-access health system. Men who underwent prostatectomy at 1 of 6 Veterans Affairs hospitals in the Shared Equal Access Regional Cancer Hospital database between 2005 and 2015 were reviewed. The prognostic ability of biopsy GG was examined using Cox models. Interactions between GG and race also were tested. In total, 2509 men were identified who had data available on biopsy Gleason scores, covariates, and follow-up. The cohort included men with GG 1 (909 patients; 36.2%), GG 2 (813 patients; 32.4%), GG 3 (398 patients; 15.9%), GG 4 (279 patients; 11.1%), and GG 5 (110 patients; 4.4%) prostate cancer. The cohort included 1002 African American men (41%). The median follow-up was 60 months (interquartile range, 33-90 months). Higher GG was associated with higher clinical stage, older age, more recent surgery, and surgical center (P < .001) as well as increased biochemical recurrence, secondary therapy, castration-resistant prostate cancer, metastases, and prostate cancer-specific mortality (all P < .001). There were no significant interactions with race in predicting measured outcomes. The 5-tier GG system predicted multiple long-term endpoints after radical prostatectomy in an equal-access health system. The predictive value was consistent across races. Cancer 2017;123:4122-4129. © 2017 American Cancer Society. © 2017 American Cancer Society.

Naringenin-Induced Apoptotic Cell Death in Prostate Cancer Cells Is Mediated via the PI3K/AKT and MAPK Signaling Pathways.

PubMed

Lim, Whasun; Park, Sunwoo; Bazer, Fuller W; Song, Gwonhwa

2017-05-01

Prostate cancer is the most common cancer in men and the second most common cause of cancer-related deaths in men. Although, various drugs targeting the androgen receptor are normally used, the patients frequently undergo recurrence of the disease. To overcome these limitations, natural compounds have been researched for evidence that they suppress progression and metastasis of various cancer cells. In the present study, we investigated effects of naringenin, a natural anti-oxidant flavonoid derived from citrus, on prostate cancer cells (PC3 and LNCaP). Results of present study with PC3 and LNCaP cells revealed that naringenin inhibited proliferation and migration, while inducing apoptosis and ROS production by those cells. In addition, naringenin-induced loss of mitochondrial membrane potential and increased Bax and decreased Bcl-2 proteins in PC3 cells, but not LNCaP cells. In a dose-dependent manner, naringenin decreased phosphorylation of ERK1/2, P70S6K, S6, and P38 in PC3 cells, and reduced phosphorylation of ERK1/2, P53, P38, and JNK proteins in LNCaP cells. However, naringenin activated phosphorylation of AKT in both PC3 and LNCaP cells. Then, targeted signaling proteins associated with viability of PC3 and LNCaP cells were analyzed using pharmacological inhibitors of AKT and ERK1/2 cell signaling pathways. Moreover, we compared the apoptotic effects of naringenin and paclitaxel alone and in combination to find that naringenin enhanced the efficiency of paclitaxel to suppress progression of prostate cancer cell lines. Collectively, these results indicate that naringenin is a potential chemotherapeutic agent for treatment of prostate cancer. J. Cell. Biochem. 118: 1118-1131, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Longitudinal regret after treatment for low- and intermediate-risk prostate cancer.

PubMed

Hurwitz, Lauren M; Cullen, Jennifer; Kim, Daniel J; Elsamanoudi, Sally; Hudak, Jane; Colston, Maryellen; Travis, Judith; Kuo, Huai-Ching; Rice, Kevin R; Porter, Christopher R; Rosner, Inger L

2017-11-01

Prostate cancer patients diagnosed with low- and intermediate-risk disease have several treatment options. Decisional regret after treatment is a concern, especially when poor oncologic outcomes or declines in health-related quality of life (HRQoL) occur. This study assessed determinants of longitudinal decisional regret in prostate cancer patients attending a multidisciplinary clinic and treated with radical prostatectomy (RP), external beam radiation therapy (EBRT), brachytherapy (BT), or active surveillance (AS). Patients newly diagnosed with prostate cancer at the Walter Reed National Military Medical Center who attended a multidisciplinary clinic were enrolled into a prospective study from 2006 to 2014. The Decision Regret Scale was administered at 6, 12, 24, and 36 months posttreatment. HRQoL was also assessed at regular intervals using the Expanded Prostate Cancer Index Composite and 36-item RAND Medical Outcomes Study Short Form questionnaires. Adjusted probabilities of reporting regret were estimated via multivariable logistic regression fitted with generalized estimating equations. A total of 652 patients met the inclusion criteria (395 RP, 141 EBRT, 41 BT, 75 AS). Decisional regret was consistently low after all of these treatments. In multivariable models, only African American race (odds ratio, 1.67; 95% confidence interval, 1.12-2.47) was associated with greater regret across time. Age and control preference were marginally associated with regret. Regret scores were similar between RP patients who did and did not experience biochemical recurrence. Declines in HRQoL were weakly correlated with greater decisional regret. In the context of a multidisciplinary clinic, decisional regret did not differ significantly between treatment groups but was greater in African Americans and those reporting poorer HRQoL. Cancer 2017;123:4252-4258. © 2017 American Cancer Society. © 2017 American Cancer Society.

Ex vivo metabolic fingerprinting identifies biomarkers predictive of prostate cancer recurrence following radical prostatectomy.

PubMed

Braadland, Peder R; Giskeødegård, Guro; Sandsmark, Elise; Bertilsson, Helena; Euceda, Leslie R; Hansen, Ailin F; Guldvik, Ingrid J; Selnæs, Kirsten M; Grytli, Helene H; Katz, Betina; Svindland, Aud; Bathen, Tone F; Eri, Lars M; Nygård, Ståle; Berge, Viktor; Taskén, Kristin A; Tessem, May-Britt

2017-11-21

Robust biomarkers that identify prostate cancer patients with high risk of recurrence will improve personalised cancer care. In this study, we investigated whether tissue metabolites detectable by high-resolution magic angle spinning magnetic resonance spectroscopy (HR-MAS MRS) were associated with recurrence following radical prostatectomy. We performed a retrospective ex vivo study using HR-MAS MRS on tissue samples from 110 radical prostatectomy specimens obtained from three different Norwegian cohorts collected between 2002 and 2010. At the time of analysis, 50 patients had experienced prostate cancer recurrence. Associations between metabolites, clinicopathological variables, and recurrence-free survival were evaluated using Cox proportional hazards regression modelling, Kaplan-Meier survival analyses and concordance index (C-index). High intratumoural spermine and citrate concentrations were associated with longer recurrence-free survival, whereas high (total-choline+creatine)/spermine (tChoCre/Spm) and higher (total-choline+creatine)/citrate (tChoCre/Cit) ratios were associated with shorter time to recurrence. Spermine concentration and tChoCre/Spm were independently associated with recurrence in multivariate Cox proportional hazards modelling after adjusting for clinically relevant risk factors (C-index: 0.769; HR: 0.72; P=0.016 and C-index: 0.765; HR: 1.43; P=0.014, respectively). Spermine concentration and tChoCre/Spm ratio in prostatectomy specimens were independent prognostic markers of recurrence. These metabolites can be noninvasively measured in vivo and may thus offer predictive value to establish preoperative risk assessment nomograms.

68Ga-PSMA-11 PET/CT Interobserver Agreement for Prostate Cancer Assessments: An International Multicenter Prospective Study.

PubMed

Fendler, Wolfgang Peter; Calais, Jeremie; Allen-Auerbach, Martin; Bluemel, Christina; Eberhardt, Nina; Emmett, Louise; Gupta, Pawan; Hartenbach, Markus; Hope, Thomas A; Okamoto, Shozo; Pfob, Christian Helmut; Pöppel, Thorsten D; Rischpler, Christoph; Schwarzenböck, Sarah; Stebner, Vanessa; Unterrainer, Marcus; Zacho, Helle D; Maurer, Tobias; Gratzke, Christian; Crispin, Alexander; Czernin, Johannes; Herrmann, Ken; Eiber, Matthias

2017-10-01

The interobserver agreement for 68 Ga-PSMA-11 PET/CT study interpretations in patients with prostate cancer is unknown. Methods: 68 Ga-PSMA-11 PET/CT was performed in 50 patients with prostate cancer for biochemical recurrence ( n = 25), primary diagnosis ( n = 10), biochemical persistence after primary therapy ( n = 5), or staging of known metastatic disease ( n = 10). Images were reviewed by 16 observers who used a standardized approach for interpretation of local (T), nodal (N), bone (Mb), or visceral (Mc) involvement. Observers were classified as having a low (<30 prior 68 Ga-PSMA-11 PET/CT studies; n = 5), intermediate (30-300 studies; n = 5), or high level of experience (>300 studies; n = 6). Histopathology ( n = 25, 50%), post-external-beam radiation therapy prostate-specific antigen response ( n = 15, 30%), or follow-up PET/CT ( n = 10, 20%) served as a standard of reference. Observer groups were compared by overall agreement (% patients matching the standard of reference) and Fleiss' κ with mean and corresponding 95% confidence interval (CI). Results: Agreement among all observers was substantial for T (κ = 0.62; 95% CI, 0.59-0.64) and N (κ = 0.74; 95% CI, 0.71-0.76) staging and almost perfect for Mb (κ = 0.88; 95% CI, 0.86-0.91) staging. Level of experience positively correlated with agreement for T (κ = 0.73/0.66/0.50 for high/intermediate/low experience, respectively), N (κ = 0.80/0.76/0.64, respectively), and Mc staging (κ = 0.61/0.46/0.36, respectively). Interobserver agreement for Mb was almost perfect irrespective of prior experience (κ = 0.87/0.91/0.88, respectively). Observers with low experience, when compared with intermediate and high experience, demonstrated significantly lower median overall agreement (54% vs. 66% and 76%, P = 0.041) and specificity for T staging (73% vs. 88% and 93%, P = 0.032). Conclusion: The interpretation of 68 Ga-PSMA-11 PET/CT for prostate cancer staging is highly consistent among observers with high levels of experience, especially for nodal and bone assessments. Initial training on at least 30 patient cases is recommended to ensure acceptable performance. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Proteomic Profiling of Exosomes Leads to the Identification of Novel Biomarkers for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duijvesz, Diederick; Burnum-Johnson, Kristin E.; Gritsenko, Marina A.

Introduction: Current markers for prostate cancer, such as PSA lack specificity. Therefore, novel biomarkers are needed. Unfortunately, biomarker discovery from body fluids is often hampered by the high abundance of many proteins unrelated to disease. An attractive alternative biomarker discovery approach is the isolation of small vesicles (exosomes, ~100 nm). They contain proteins that are specific to the tissue from which they are derived and therefore can be considered as treasure chests for disease-specific marker discovery. Profiling prostate cancer-derived exosomes could reveal new markers for this malignancy. Materials and Methods: Exosomes were isolated from 2 immortalized primary prostate epithelial cellsmore » (PNT2C2 and RWPE-1) and 2 PCa cell lines (PC346C and VCaP) by ultracentrifugation. Proteomic analyses utilized a nanoLC coupled with an LTQ-Orbitrap operated in tandem MS (MS/MS) mode, followed by the Accurate Mass and Time (AMT) tag approach. Exosomal proteins were validated by Western blotting. A Tissue Micro Array, containing 481 different PCa samples (radical prostatectomy), was used to correlate candidate markers with several clinical-pathological parameters such as PSA, Gleason score, biochemical recurrence, and (PCa-related) death. Results: Proteomic characterization resulted in the identification of 263 proteins by at least 2 peptides. Specifically analysis of exosomes from PNT2C2, RWPE-1, PC346C, and VCaP identified 248, 233, 169, and 216 proteins, respectively. Statistical analyses revealed 52 proteins differently expressed between PCa and control cells, 9 of which were more abundant in PCa. Validation by Western blotting confirmed a higher abundance of FASN, XPO1 and PDCD6IP (ALIX) in PCa exosomes. The Tissue Micro 4 Array showed strong correlation of higher Gleason scores and local recurrence with increased cytoplasmic XPO1 (P<0.001). Conclusions: Differentially abundant proteins of cell line-derived exosomes make a clear subdivision between benign and malignant origin. Validation showed a preferential abundance of PDCD6IP, FASN and XPO1. Cytoplasmic XPO1 is the most promising candidate biomarker.« less

High-intensity focused ultrasound (HIFU) in prostate cancer: a single centre experience in patients with low, intermediate or high-risk of progression.

PubMed

Callea, Andrea; Piccinni, Roberto; Zizzi, Vito; Sblendorio, Domenico; Berardi, Bartolomeo; Tempesta, Antonio; Gala, Francesco Giuseppe; Traficante, Antonio

2010-12-01

High-intensity focused ultrasound (HIFU) is a minimally invasive treatment based on thermal ablation of tissues which are warmed up to 85 degrees C in the focal area. Clinical studies have shown such treatment modality to be safe and effective in the management of localised prostate cancer as well as of local recurrences after radical prostatectomy or radiotherapy. From May 2002 to June 2010, 171 patients with no previous treatment for prostate cancer, aged 44 to 86 years (mean 74.7) underwent 197 HIFU treatments; 22 patients needed a second treatment as the first was incomplete (4 patients) or because of recurrence (18 patients). The prognosis subgroups were defined as low-risk in 29 patients (clinical stage T1-T2a, PSA < or = 10 ng/mL and Gleason score lower than 7), intermediate-risk in 47 patients (clinical stage T2b or PSA 10 - 20 ng/mL or Gleason score of 7), and high-risk in 95 patients (clinical stage > or = T2c or PSA > 20 ng/mL or Gleason score higher than 7). At a mean follow-up of 67.9 months, biochemical success rate (PSA constantly < 0.5 ng/ml) was obtained in 84.2% of low and intermediate risk patients and in 43.1% of high risk patients; post-treatment biopsies (6 months after treatment) revealed no residual tumour in 93.4% of low or intermediate risk patients and in 63.1% of high risk patients. Radical prostatectomy remains the "gold standard" for localised prostate cancer. However, HIFU seems to be a promising alternative and less invasive treatment modality with an encouraging success rate, at least in the short-term, in patients with low and medium risk of progression, not candidates for radical surgery; in cancers with clinical stage > or = T2c, or PSA > 20 ng/mL, or Gleason score higher than 7 seems to get good results in about half of patients.

Higher-Than-Conventional Radiation Doses in Localized Prostate Cancer Treatment: A Meta-analysis of Randomized, Controlled Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Viani, Gustavo Arruda; Stefano, Eduardo Jose; Afonso, Sergio Luis

2009-08-01

Purpose: To determine in a meta-analysis whether the outcomes in men with localized prostate cancer treated with high-dose radiotherapy (HDRT) are better than those in men treated with conventional-dose radiotherapy (CDRT), by quantifying the effect of the total dose of radiotherapy on biochemical control (BC). Methods and Materials: The MEDLINE, EMBASE, CANCERLIT, and Cochrane Library databases, as well as the proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing HDRT with CDRT for localized prostate cancer. To evaluate the dose-response relationship, we conducted a meta-regression analysis of BC ratios by means of weighted linear regression. Results:more » Seven RCTs with a total patient population of 2812 were identified that met the study criteria. Pooled results from these RCTs showed a significant reduction in the incidence of biochemical failure in those patients with prostate cancer treated with HDRT (p < 0.0001). However, there was no difference in the mortality rate (p = 0.38) and specific prostate cancer mortality rates (p = 0.45) between the groups receiving HDRT and CDRT. However, there were more cases of late Grade >2 gastrointestinal toxicity after HDRT than after CDRT. In the subgroup analysis, patients classified as being at low (p = 0.007), intermediate (p < 0.0001), and high risk (p < 0.0001) of biochemical failure all showed a benefit from HDRT. The meta-regression analysis also detected a linear correlation between the total dose of radiotherapy and biochemical failure (BC = -67.3 + [1.8 x radiotherapy total dose in Gy]; p = 0.04). Conclusions: Our meta-analysis showed that HDRT is superior to CDRT in preventing biochemical failure in low-, intermediate-, and high-risk prostate cancer patients, suggesting that this should be offered as a treatment for all patients, regardless of their risk status.« less

Does Local Recurrence of Prostate Cancer After Radiation Therapy Occur at the Site of Primary Tumor? Results of a Longitudinal MRI and MRSI Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arrayeh, Elnasif; Westphalen, Antonio C.; Kurhanewicz, John

2012-04-01

Purpose: To determine if local recurrence of prostate cancer after radiation therapy occurs at the same site as the primary tumor before treatment, using longitudinal magnetic resonance (MR) imaging and MR spectroscopic imaging to assess dominant tumor location. Methods and Materials: This retrospective study was HIPAA compliant and approved by our Committee on Human Research. We identified all patients in our institutional prostate cancer database (1996 onward) who underwent endorectal MR imaging and MR spectroscopic imaging before radiotherapy for biopsy-proven prostate cancer and again at least 2 years after radiotherapy (n = 124). Two radiologists recorded the presence, location, andmore » size of unequivocal dominant tumor on pre- and postradiotherapy scans. Recurrent tumor was considered to be at the same location as the baseline tumor if at least 50% of the tumor location overlapped. Clinical and biopsy data were collected from all patients. Results: Nine patients had unequivocal dominant tumor on both pre- and postradiotherapy imaging, with mean pre- and postradiotherapy dominant tumor diameters of 1.8 cm (range, 1-2.2) and 1.9 cm (range, 1.4-2.6), respectively. The median follow-up interval was 7.3 years (range, 2.7-10.8). Dominant recurrent tumor was at the same location as dominant baseline tumor in 8 of 9 patients (89%). Conclusions: Local recurrence of prostate cancer after radiation usually occurs at the same site as the dominant primary tumor at baseline, suggesting supplementary focal therapy aimed at enhancing local tumor control would be a rational addition to management.« less

Downregulation of microRNA‑574 in cancer stem cells causes recurrence of prostate cancer via targeting REL.

PubMed

Lai, Xiaodong; Guo, Yanchun; Guo, Zhitao; Liu, Ruibao; Wang, Xunguo; Wang, Fang

2016-12-01

miR‑574‑5p has been reported involved in the pathogenesis of numerous human malignancies such as colorectal and lung cancer. In this study, we aimed to explore the roles of REL and miR‑574 in the recurrence of prostate cancer (PCa) and to identify the underlying molecular mechanisms. Our literature search found that miR‑574 is regulated in cancer stem cells (CSCs), and next we used the microRNA (miRNA) database (www.mirdb.org) to find REL as a target of miR‑574. Luciferase assay was performed to verify the miRNA/target relationship. Oligo-transfection, real‑time PCR and western blot analysis were used to support the conclusions. We validated REL to be the direct gene via luciferase reporter assay system, and real‑time PCR and western blot analysis were also conducted to study the mRNA and protein expression level of REL between different groups (recurrence and non‑recurrence) or cells treated with scramble control, miR‑574 mimics, REL siRNA and miR‑574 inhibitors, indicating the negative regulatory relationship between miR‑574 and REL. We also investigated the relative viability of prostate CSCs when transfected with scramble control, miR‑574 mimics, REL siRNA and miR‑574 inhibitors to validate miR‑574 to be positively interfering with the viability of prostate CSCs. We then investigated the relative apoptosis of prostate CSCs when transfected with scramble control, miR‑574 mimics, REL siRNA and miR‑574 inhibitors. The results showed miR‑574 inhibited apoptosis. In conclusion, miR‑574 might be a novel prognostic and therapeutic target in the management of PCa recurrence.

NADiA ProsVue prostate-specific antigen slope is an independent prognostic marker for identifying men at reduced risk of clinical recurrence of prostate cancer after radical prostatectomy.

PubMed

Moul, Judd W; Lilja, Hans; Semmes, O John; Lance, Raymond S; Vessella, Robert L; Fleisher, Martin; Mazzola, Clarisse; Sarno, Mark J; Stevens, Barbara; Klem, Robert E; McDermed, Jonathan E; Triebell, Melissa T; Adams, Thomas H

2012-12-01

To validate the hypothesis that men displaying serum prostate-specific antigen (PSA) slopes ≤ 2.0 pg/mL/mo after prostatectomy, measured using a new immuno-polymerase chain reaction diagnostic test (NADiA ProsVue), have a reduced risk of clinical recurrence as determined by positive biopsy, imaging findings, or death from prostate cancer. From 4 clinical sites, we selected a cohort of 304 men who had been followed up for 17.6 years after prostatectomy for clinical recurrence. We assessed the prognostic value of a PSA slope cutpoint of 2.0 pg/mL/mo against established risk factors to identify men at low risk of clinical recurrence using uni- and multivariate Cox proportional hazards regression and Kaplan-Meier analyses. The univariate hazard ratio of a PSA slope >2.0 pg/mL/mo was 18.3 (95% confidence interval 10.6-31.8) compared with a slope ≤ 2.0 pg/mL/mo (P <.0001). The median disease-free survival interval was 4.8 years vs >10 years in the 2 groups (P <.0001). The multivariate hazard ratio for PSA slope with the covariates of preprostatectomy PSA, pathologic stage, and Gleason score was 9.8 (95% confidence interval 5.4-17.8), an 89.8% risk reduction for men with PSA slopes ≤ 2.0 pg/mL/mo (P <.0001). The Gleason score (<7 vs ≥ 7) was the only other significant predictor (hazard ratio 5.4, 95% confidence interval 2.1-13.8, P = .0004). Clinical recurrence after radical prostatectomy is difficult to predict using established risk factors. We have demonstrated that a NADiA ProsVue PSA slope of ≤ 2.0 pg/mL/mo after prostatectomy is prognostic for a reduced risk of prostate cancer recurrence and adds predictive power to the established risk factors. Copyright © 2012 Elsevier Inc. All rights reserved.

Regional hyperthermia in conjunction with definitive radiotherapy against recurrent or locally advanced prostate cancer T3 pN0 M0.

PubMed

Tilly, Wolfgang; Gellermann, Johanna; Graf, Reinhold; Hildebrandt, Bert; Weissbach, Lothar; Budach, Volker; Felix, Roland; Wust, Peter

2005-01-01

Since long-term results of the standard treatment of locally advanced or recurrent prostatic carcinoma are unsatisfactory, the role for additional regional hyperthermia was evaluated in a phase I/II study. From 08/1996 to 03/2000, 22 patients were treated by a standard irradiation regimen (68.4 Gy) in combination with regional hyperthermia (weekly, five to six times), and five of 22 patients received short-term (neoadjuvant) hormonal treatment. Of these, 15 patients had primary prostatic carcinoma T3 pN0 M0 and seven a histologically confirmed local recurrence after radical prostatectomy. Feasibility of hyperthermia, and acute/late toxicity as well as long-term follow-up (prostate- specific antigen [PSA] control, overall survival) were analyzed. Clinical endpoints were correlated with thermal parameters. Mean maximum temperatures along the urethra of 41.4 degrees C (41.0 degrees C for the recurrences), and mean T(90) values of 40.7 degrees C could be achieved. Severe acute toxicity of grade 3 occurred at the rectum in three, at the urethra in four, at the intestine in one, and a burn induced by hyperthermia in one of 22 patients. Late toxicity was only observed rectally in one patient (grade 3) and at the urethra in two patients (grade 2). There was no correlation between thermal parameters and any toxicity. The survival curves showed a PSA control for primary prostatic carcinoma > 50% after 6 years, but no long-term PSA control for the recurrences. Overall survival after 6 years was 95% for primary carcinoma, and 60% for the recurrences. There was a clear correlation between higher temperatures or thermal doses with long-term PSA control. Regional hyperthermia might be a low-toxicity approach to increase PSA control of common treatment schedules. Further evaluation, in particular employing improved hyperthermia technology, is worthwhile.

Effect of age on biochemical disease-free outcome in patients with T1-T3 prostate cancer treated with definitive radiotherapy in an equal-access health care system: a radiation oncology report of the Department of Defense Center for Prostate Disease Research.

PubMed

Johnstone, Peter A S; Riffenburgh, Robert H; Moul, Judd W; Sun, Leon; Wu, Hongyu; McLeod, David G; Kane, Christopher J; Martin, Douglas D; Kusuda, Leo; Lance, Raymond; Douglas, Robert; Donahue, Timothy; Beat, Michael G; Foley, John; Chung, Andrew; Soderdahl, Douglas; Do, Jason; Amling, Christopher L

2003-03-15

It has traditionally been a common perception that young age is a negative prognostic factor in prostate cancer (CaP). Furthermore, many urologists believe that younger patients are better suited to surgery rather than radiotherapy (RT) because of this perception. However, the data on the effect of age on outcome in patients with CaP are unclear. The records of the Department of Defense Center for Prostate Disease Research were queried for the biochemical disease-free results of patients after definitive RT and analyzed by age. The records of 1018 patients with T1-T3 CaP treated with definitive RT between 1988 and 2000 were reviewed. The records of patients receiving adjuvant hormonal therapy or adjuvant or salvage RT postoperatively were excluded. Biochemical failure was calculated by the American Society for Therapeutic Radiology and Oncology criteria. The median potential follow-up was 85.3 months as of December 31, 2001. Age did not affect biochemical disease-free survival significantly when considered as <60 vs. >/=60 years (p = 0.646), by decade (p = 0.329), or as a continuous variable (correlation coefficient r = 0.017, regression slope = 0.007, with p = 0.588 and R(2) < 0.001). Using multiple regression analysis, age was still not significant (p = 0.408). Other variables analyzed were pretreatment prostate-specific antigen level (p < 0.001), Gleason sum (p = 0.023), stage (p = 0.828), and RT dose (p = 0.033). Age and biochemical disease-free survival after RT for CaP are not related. Age may not be a valid factor in choosing between primary treatment options for CaP.

The long tail of oncogenic drivers in prostate cancer.

PubMed

Armenia, Joshua; Wankowicz, Stephanie A M; Liu, David; Gao, Jianjiong; Kundra, Ritika; Reznik, Ed; Chatila, Walid K; Chakravarty, Debyani; Han, G Celine; Coleman, Ilsa; Montgomery, Bruce; Pritchard, Colin; Morrissey, Colm; Barbieri, Christopher E; Beltran, Himisha; Sboner, Andrea; Zafeiriou, Zafeiris; Miranda, Susana; Bielski, Craig M; Penson, Alexander V; Tolonen, Charlotte; Huang, Franklin W; Robinson, Dan; Wu, Yi Mi; Lonigro, Robert; Garraway, Levi A; Demichelis, Francesca; Kantoff, Philip W; Taplin, Mary-Ellen; Abida, Wassim; Taylor, Barry S; Scher, Howard I; Nelson, Peter S; de Bono, Johann S; Rubin, Mark A; Sawyers, Charles L; Chinnaiyan, Arul M; Schultz, Nikolaus; Van Allen, Eliezer M

2018-05-01

Comprehensive genomic characterization of prostate cancer has identified recurrent alterations in genes involved in androgen signaling, DNA repair, and PI3K signaling, among others. However, larger and uniform genomic analysis may identify additional recurrently mutated genes at lower frequencies. Here we aggregate and uniformly analyze exome sequencing data from 1,013 prostate cancers. We identify and validate a new class of E26 transformation-specific (ETS)-fusion-negative tumors defined by mutations in epigenetic regulators, as well as alterations in pathways not previously implicated in prostate cancer, such as the spliceosome pathway. We find that the incidence of significantly mutated genes (SMGs) follows a long-tail distribution, with many genes mutated in less than 3% of cases. We identify a total of 97 SMGs, including 70 not previously implicated in prostate cancer, such as the ubiquitin ligase CUL3 and the transcription factor SPEN. Finally, comparing primary and metastatic prostate cancer identifies a set of genomic markers that may inform risk stratification.

[11C]choline-PET-guided helical tomotherapy and estramustine in a patient with pelvic-recurrent prostate cancer: local control and toxicity profile after 24 months.

PubMed

Alongi, Filippo; Schipani, Stefano; Samanes Gajate, Ana Maria; Rosso, Alberto; Cozzarini, Cesare; Fiorino, Claudio; Alongi, Pierpaolo; Picchio, Maria; Gianolli, Luigi; Messa, Cristina; Di Muzio, Nadia

2010-01-01

[11C]choline positron emission tomograhy can be useful to detect metastatic disease and to localize isolated lymph node relapse after primary treatment in case of prostate-specific antigen failure. In case of lymph node failure in prostate cancer patients, surgery or radiotherapy can be proposed with a curative intent. Some reports have suggested that radiotherapy could have a role in local control of oligometastatic lymph node disease. This is the first reported case of [11C]choline positron emission tomography-guided helical tomotherapy concomitant with estramustine for the treatment of pelvic-recurrent prostate cancer. At 24 months after the end of helical tomotherapy, prostate-specific antigen was undetectable and no late toxicities were recorded. A disease-free survival of 24 months, in the absence of any type of systemic therapy, is uncommon in metastatic prostate cancer. The therapeutic approach of the case report is discussed and a literature review on the issue is presented.

Prostate cancer progression and mortality: a review of diet and lifestyle factors.

PubMed

Peisch, Sam F; Van Blarigan, Erin L; Chan, June M; Stampfer, Meir J; Kenfield, Stacey A

2017-06-01

To review and summarize evidence on the role of diet and lifestyle factors and prostate cancer progression, with a specific focus on habits after diagnosis and the risk of subsequent disease recurrence, progression, or death. Given the well-documented heterogeneity of prostate cancer and the long survivorship of the majority of diagnoses, our goal was to summarize and describe modifiable risk factors for clinically relevant prostate cancer. We focused where possible on epidemiologic studies of post-diagnostic habits and prostate cancer progression, defined as recurrence (e.g., PSA risk, secondary treatment), metastasis, or death. Where data were limited, we also describe evidence on risk factors and indicators of prostate cancer aggressiveness at diagnosis. A variety of dietary and lifestyle factors appear to affect prostate cancer progression. Several generally widely recommended lifestyle factors such as not smoking, maintaining a healthy body weight, and regular vigorous physical exercise also appear to affect prostate cancer progression. Several dietary factors, such as tomato sauce/lycopene, cruciferous vegetables, healthy sources of vegetable fats, and coffee, may also have a role in reducing risk of prostate cancer progression. Diet and lifestyle factors, in particular exercise and smoking cessation, may reduce the risk of prostate cancer progression and death. These promising findings warrant further investigation, as their overall impact might be large.

Prostate-specific antigen bounce after intensity-modulated radiotherapy for prostate cancer.

PubMed

Sheinbein, Courtney; Teh, Bin S; Mai, Wei Y; Grant, Walter; Paulino, Arnold; Butler, E Brian

2010-09-01

To report prostate-specific antigen (PSA) bounce in patients treated with intensity-modulated radiotherapy (IMRT) alone. Previous studies have reported PSA bounce in prostate cancer patients treated with conventional radiotherapy, 3D conformal radiotherapy, and permanent seed brachytherapy. From January 1997 to July 2002, 102 patients with clinically localized prostate cancer were treated with IMRT alone. No patients received androgen ablation. PSA bounce was defined as a PSA increase of at least 0.4 ng/mL, followed by any PSA decrease. Biochemical failure was defined by both the American Society for Therapeutic Radiology and Oncology 1996 and 2006 consensus definitions. The median follow-up was 76 months. The median length of time until the first PSA bounce was 13.6 months. Thirty-three patients (32.4%) had at least 1 PSA bounce, with 25 (24.5%) having 1 bounce; 6 (5.9%), 2 bounces; and 2 (2.0%), 4 bounces. PSA bounce was not significantly associated with biochemical no evidence of disease survival, clinical stage, pretreatment PSA, Gleason combined score, prostate planning target volume, PSA nadir, or mean dose to the prostate. The rate of PSA bounce in patients aged ≤ 70 and > 70 years was 44.4% and 22.8%, respectively (P = .032). Our patient series is the first report on PSA bounce in patients treated with IMRT. Our study confirms that the majority of patients with a bouncing PSA remain biochemically and clinically free of disease with extended follow-up. Copyright © 2010 Elsevier Inc. All rights reserved.

Predictors of recurrence in pheochromocytoma.

PubMed

Press, Danielle; Akyuz, Muhammet; Dural, Cem; Aliyev, Shamil; Monteiro, Rosebel; Mino, Jeff; Mitchell, Jamie; Hamrahian, Amir; Siperstein, Allan; Berber, Eren

2014-12-01

The recurrence rate of pheochromocytoma after adrenalectomy is 6.5-16.5%. This study aims to identify predictors of recurrence and optimal biochemical testing and imaging for detecting the recurrence of pheochromocytoma. In this retrospective study we reviewed all patients who underwent adrenalectomy for pheochromocytoma during a 14-year period at a single institution. One hundred thirty-five patients had adrenalectomy for pheochromocytoma. Eight patients (6%) developed recurrent disease. The median time from initial operation to diagnosis of recurrence was 35 months. On multivariate analysis, tumor size >5 cm was an independent predictor of recurrence. One patient with recurrence died, 4 had stable disease, 2 had progression of disease, and 1 was cured. Recurrence was diagnosed by increases in plasma and/or urinary metanephrines and positive imaging in 6 patients (75%), and by positive imaging and normal biochemical levels in 2 patients (25%). Patients with large tumors (>5 cm) should be followed vigilantly for recurrence. Because 25% of patients with recurrence had normal biochemical levels, we recommend routine imaging and testing of plasma or urinary metanephrines for prompt diagnosis of recurrence. Copyright © 2014 Elsevier Inc. All rights reserved.

The role of positron emission tomography/computed tomography imaging with radiolabeled choline analogues in prostate cancer.

PubMed

Navarro-Pelayo Láinez, M M; Rodríguez-Fernández, A; Gómez-Río, M; Vázquez-Alonso, F; Cózar-Olmo, J M; Llamas-Elvira, J M

2014-11-01

prostate cancer is the most frequent solid malignant tumor in Western Countries. Positron emission tomography/x-ray computed tomography imaging with radiolabeled choline analogues is a useful tool for restaging prostate cancer in patients with rising prostate-specific antigen after radical treatment (in whom conventional imaging techniques have important limitations) as well as in the initial assessment of a selected group of prostate cancer patients. For this reason a literature review is necessary in order to evaluate the usefulness of this imaging test for the diagnosis and treatment of prostate cancer. a MEDLINE (PubMed way) literature search was performed using the search parameters: «Prostate cancer» and «Choline-PET/CT». Other search terms were «Biochemical failure» and/or «Staging» and/or «PSA kinetics». English and Spanish papers were selected; original articles, reviews, systematic reviews and clinical guidelines were included. according to available data, radiolabeled choline analogues plays an important role in the management of prostate cancer, especially in biochemical relapse because technique accuracy is properly correlated with prostate-specific antigen values and kinetics. Although is an emerging diagnostic technique useful in treatment planning of prostate cancer, final recommendations have not been submitted. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

[High-intensity focused ultrasound (HIFU) for the prostate cancer treatment: 5-year resuts].

PubMed

Shaplysin, L V; Solov, V A; Vosdvizhenskiĭ, M O; Khametov, R Z

2013-01-01

During 2007-2012 748 patients with prostate cancer (PCa) underwent ultrasound ablation (HIFU). Patients were divided into 3 groups according to the prevalence and risk of disease progression: low risk (localized prostate cancer, 465 (62%) of patients) stage T1-2N0M0, total Gleason score < or = 6, the level of prostate-specific antigen (PSA) less than 20 ng/ml), high risk (locally advanced prostate cancer, 251 (34%) of patients)--stage T2-3N0M0, total Gleason score < or = 9, the PSA level from 20 to 60 ng/ml, the presence of local recurrence after radical prostatectomy (RPE) and external beam radiation (EBRT)--32 (4%) patients. Median follow-up after HIFU-therapy was 36 (3-54) months. At 12 and 48 months after treatment in patients with a low risk of progression median PSA was 0.2 and 0.5 ng/ml, in the group with a high risk 0.8 and 1.2 ng/ml, in patients with local recurrence after RPE and EBRT--0.5 and 1.7 ng/ml respectively. Generally HIFU treatment was successful in 90.9% of patients. It is shown that HIFU is safe minimally invasive treatment for localizes and locally advanced prostate cancer. It can be successfully performed in patients with local recurrence after RPE and EBRT.

Impact of hormonal therapy on intermediate risk prostate cancer treated with combination brachytherapy and external beam irradiation.

PubMed

Stock, Richard G; Yalamanchi, Swati; Yamalachi, Swati; Hall, Simon J; Stone, Nelson N

2010-02-01

We assessed the impact of androgen suppressive therapy on biochemical failure in patients with intermediate risk prostate cancer treated with brachytherapy and external beam irradiation. From 1994 to 2006, 432 patients with intermediate risk prostate cancer as defined by the National Comprehensive Cancer Network were treated with low dose rate brachytherapy and external beam irradiation with or without 9 months of androgen suppressive therapy. Gleason score was 7 in 76% of cases and prostate specific antigen was 1.4 to 20 ng/ml (median 7.6). Of the patients 350 received androgen suppressive therapy and 82 did not. The biologically effective dose was 142 to 280 Gy2 (median 206). Followup was 23 to 155 months (median 56). The overall 8-year biochemical failure-free rate using the Phoenix definition in patients with vs without androgen suppressive therapy was 92% vs 92% (p = 0.4). The therapy had no significant impact on the biochemical failure-free rate in patients with Gleason score 7 (92% vs 90.5%, p = 0.55), prostate specific antigen 10 to 20 ng/ml (92% vs 100%, p = 0.32), T2b-T2c disease (89.5% vs 97%, p = 0.27) and more than 1 intermediate risk feature (90% vs 100%, p = 0.2). We addressed the relative importance of radiation dose vs hormonal therapy for intermediate risk prostate cancer. With high biologically effective dose combination treatment androgen suppressive therapy did not have a significant impact on the 8-year biochemical failure-free rate. We question its routine use in this setting. Copyright 2010 American Urological Association. Published by Elsevier Inc. All rights reserved.

Metastatic prostate cancer in the modern era of PSA screening

PubMed Central

Fontenot, Philip A.; Nehra, Avinash; Parker, William; Wyre, Hadley; Mirza, Moben; Duchene, David A.; Holzbeierlein, Jeffrey; Thrasher, James Brantley; Veldhuizen, Peter Van; Lee, Eugene K.

2017-01-01

ABSTRACT Introduction To characterize initial presentation and PSA screening status in a contemporary cohort of men treated for metastatic prostate cancer at our institution. Materials and methods We reviewed records of 160 men treated for metastatic prostate cancer between 2008-2014 and assessed initial presentation, categorizing patients into four groups. Groups 1 and 2 presented with localized disease and received treatment. These men suffered biochemical recurrence late (>1 year) or earlier (<1 year), respectively, and developed metastases. Groups 3 and 4 had asymptomatic and symptomatic metastases at the outset of their diagnosis. Patients with a first PSA at age 55 or younger were considered to have guideline-directed screening. Results Complete records were available on 157 men for initial presentation and 155 men for PSA screening. Groups 1, 2, 3 and 4 included 27 (17%), 7 (5%), 69 (44%) and 54 (34%) patients, respectively. Twenty (13%) patients received guideline-directed PSA screening, 5/155 (3%) patients presented with metastases prior to age 55 with their first PSA, and 130/155 (84%) had their first PSA after age 55, of which 122/130 (94%) had metastasis at the time of diagnosis. Conclusion Despite widespread screening, most men treated for metastatic prostate cancer at our institution presented with metastases rather than progressed after definitive treatment. Furthermore, 25 (16%) patients received guideline-directed PSA screening at or before age 55. These data highlight that, despite mass screening efforts, patients treated for incurable disease at our institution may not have been a result of a failed screening test, but a failure to be screened. PMID:28338310

Pretreatment Serum Testosterone and Androgen Deprivation: Effect on Disease Recurrence and Overall Survival in Prostate Cancer Patients Treated With Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taira, Al V.; Merrick, Gregory S.; Galbreath, Robert W.

Purpose: Low testosterone has been implicated as a possible adverse prognostic factor in patients with newly diagnosed prostate cancer. We evaluated the impact of pretreatment serum testosterone on survival after prostate brachytherapy. Methods and Materials: From October 2001 to November 2004, 619 patients underwent brachytherapy and 546 had a pretreatment serum testosterone level measured. Pretreatment serum testosterone levels were assigned by the following criteria: below-normal (n = 105), low normal (n = 246), mid normal (n = 132), high normal (n = 50), and above normal (n = 13). Median follow-up was 5.2 years. Cause of death was determined formore » each deceased patient. Results: Six-year biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) were 97.7%, 99.8%, and 89.2%. When comparing patients with low or low normal testosterone with those with average or higher testosterone, there was no significant difference in bPFS (97.6% vs. 98.4%; p = 0.72), CSS (99.8% vs. 100%; p = 0.72), or OS (88.9% vs. 90.8%; p = 0.73). Among patients with average and higher pretreatment testosterone, there was no significant difference in outcomes when comparing patients who did and did not receive androgen deprivation therapy (ADT). For patients with low or low normal testosterone levels, there was no significant difference in bPFS or CSS when comparing patients who did and did not receive ADT. However, there was a trend toward lower OS in patients with baseline lower testosterone levels who also received ADT (83.9% vs. 91.3%, p = 0.075). Conclusions: Low pretreatment testosterone levels alone did not affect disease recurrence or OS. Patients with baseline low testosterone who also were treated with ADT had a trend toward decreased OS.« less

New aspects of molecular imaging in prostate cancer.

PubMed

Ceci, Francesco; Castellucci, Paolo; Cerci, Juliano J; Fanti, Stefano

2017-11-01

Nowadays several new imaging modalities are available for investigating prostate cancer (PCa) such as magnet resonance imaging (MRI) in the form of whole body MRI and pelvic multiparametric MRI and positron emission tomography (PET) using choline as radiotracers. Nevertheless, these modalities proved sub-optimal accuracy for detecting PCa metastases, particularly in the recurrence setting. A new molecular probe targeting the prostate specific membrane antigen (PSMA) has been recently developed for PET imaging. PSMA, the glutamate carboxypeptidase II, is a membrane bound metallo-peptidase over-expressed in PCa cells. It has been shown that PSMA based imaging offers higher tumor detection rate compared to choline PET/CT and radiological conventional imaging, especially at very low PSA levels during biochemical recurrence. In addition PSMA, as theranostics agent, allows both radiolabeling with diagnostic (e.g. 68Ga, 18F) or therapeutic nuclides (e.g. 177Lu, 225Ac). Initial results show that PSMA-targeted radioligand therapy can potentially delay disease progression in metastatic castrate-resistant PCa. Despite still investigational, the bombesin-based radiotracers and antagonist of gastrin releasing-peptide receptor (GRP) (RM2) and anti1-amino-3-18Ffluorocyclobutane-1-carboxylic acid (18F-FACBC) are emerging as possible alternatives for investigating PCa. Considering the wide diffusion of PCa in the Europe and the United States, the presence of these new diagnostic techniques able to detect the disease with high sensitivity and specificity might have a clinical impact on the management of patients. PET/CT imaging with new radiopharmaceuticals can implement the patient management identifying lesion(s) not detectable with conventional imaging procedures. In this review article will be discussed the most promising new PET radiopharmaceuticals (68Ga-PSMA-11, 18F-FACBC, 68Ga-RM2) available at the moment, focusing the attention on their accuracy and their impact on treatment strategy. Copyright © 2017 Elsevier Inc. All rights reserved.

Detectable end of radiation prostate specific antigen assists in identifying men with unfavorable intermediate-risk prostate cancer at high risk of distant recurrence and cancer-specific mortality.

PubMed

Hayman, Jonathan; Phillips, Ryan; Chen, Di; Perin, Jamie; Narang, Amol K; Trieu, Janson; Radwan, Noura; Greco, Stephen; Deville, Curtiland; McNutt, Todd; Song, Daniel Y; DeWeese, Theodore L; Tran, Phuoc T

2018-06-01

Undetectable End of Radiation PSA (EOR-PSA) has been shown to predict improved survival in prostate cancer (PCa). While validating the unfavorable intermediate-risk (UIR) and favorable intermediate-risk (FIR) stratifications among Johns Hopkins PCa patients treated with radiotherapy, we examined whether EOR-PSA could further risk stratify UIR men for survival. A total of 302 IR patients were identified in the Johns Hopkins PCa database (178 UIR, 124 FIR). Kaplan-Meier curves and multivariable analysis was performed via Cox regression for biochemical recurrence free survival (bRFS), distant metastasis free survival (DMFS), and overall survival (OS), while a competing risks model was used for PCa specific survival (PCSS). Among the 235 patients with known EOR-PSA values, we then stratified by EOR-PSA and performed the aforementioned analysis. The median follow-up time was 11.5 years (138 months). UIR was predictive of worse DMFS and PCSS (P = 0.008 and P = 0.023) on multivariable analysis (MVA). Increased radiation dose was significant for improved DMFS (P = 0.016) on MVA. EOR-PSA was excluded from the models because it did not trend towards significance as a continuous or binary variable due to interaction with UIR, and we were unable to converge a multivariable model with a variable to control for this interaction. However, when stratifying by detectable versus undetectable EOR-PSA, UIR had worse DMFS and PCSS among detectable EOR-PSA patients, but not undetectable patients. UIR was significant on MVA among detectable EOR-PSA patients for DMFS (P = 0.021) and PCSS (P = 0.033), while RT dose also predicted PCSS (P = 0.013). EOR-PSA can assist in predicting DMFS and PCSS among UIR patients, suggesting a clinically meaningful time point for considering intensification of treatment in clinical trials of intermediate-risk men. © 2018 Wiley Periodicals, Inc.

Silodosin inhibits prostate cancer cell growth via ELK1 inactivation and enhances the cytotoxic activity of gemcitabine.

PubMed

Kawahara, Takashi; Aljarah, Ali Kadhim; Shareef, Hasanain Khaleel; Inoue, Satoshi; Ide, Hiroki; Patterson, John D; Kashiwagi, Eiji; Han, Bin; Li, Yi; Zheng, Yichun; Miyamoto, Hiroshi

2016-06-01

Biological significance of ELK1, a transcriptional factor whose phosphorylation is necessary for c-fos proto-oncogene activation, in prostate cancer remains far from fully understood. In this study, we aim to investigate the role of ELK1 in tumor growth as well as the efficacy of a selective α1A-adrenergic blocker, silodosin, in ELK1 activity in prostate cancer cells. We first immunohistochemically determined the levels of phospho-ELK1 (p-ELK1) expression in radical prostatectomy specimens. We then assessed the effects of ELK1 knockdown via short hairpin RNA and silodosin on cell proliferation, migration, and invasion in prostate cancer lines. The levels of p-ELK1 expression were significantly higher in carcinoma than in benign (P < 0.001) or high-grade prostatic intraepithelial neoplasia (HGPIN) (P = 0.002) as well as in HGPIN than in benign (P < 0.001). Kaplan-Meier and log-rank tests revealed that moderate-strong positivity of p-ELK1 in carcinomas tended to correlate with biochemical recurrence after radical prostatectomy (P = 0.098). In PC3 and DU145 expressing ELK1 (mRNA/protein) but no androgen receptor (AR), ELK1 silencing resulted in considerable decreases in the expression of c-fos as well as in cell migration/invasion and matrix metalloproteinase-2 expression, but not in cell viability. Silodosin treatment reduced the expression/activity of ELK1 in these cells as well as the viability of AR-positive LNCaP and C4-2 cells and the migration of both AR-positive and AR-negative cells, but not the viability of AR-negative or ELK1-negative cells. Interestingly, silodosin significantly increased sensitivity to gemcitabine, but not to cisplatin or docetaxel, even in AR-negative cells. ELK1 is likely to be activated in prostate cancer cells and promote tumor progression. Furthermore, silodosin that inactivates ELK1 in prostate cancer cells not only inhibits their growth but also enhances the cytotoxic activity of gemcitabine. Thus, ELK1 inhibition has the potential of being a therapeutic approach for prostate cancer. © 2016 Wiley Periodicals, Inc.

Initial multicentre experience of 68 gallium-PSMA PET/CT guided robot-assisted salvage lymphadenectomy: acceptable safety profile but oncological benefit appears limited.

PubMed

Siriwardana, Amila; Thompson, James; van Leeuwen, Pim J; Doig, Shaela; Kalsbeek, Anton; Emmett, Louise; Delprado, Warick; Wong, David; Samaratunga, Hemamali; Haynes, Anne-Maree; Coughlin, Geoff; Stricker, Phillip

2017-11-01

To evaluate the safety and short-term oncological outcomes of 68 gallium-labelled prostate-specific membrane antigen ( 68 Ga-PSMA) positron-emission tomography (PET)/computed tomography (CT)-directed robot-assisted salvage node dissection (RASND) for prostate cancer oligometastatic nodal recurrence. Between February 2014 and April 2016, 35 patients across two centres underwent RASND for 68 Ga-PSMA PET/CT-detected oligometastatic nodal recurrence. RASND was performed using targeted pelvic dissection, unilateral extended pelvic template or bilateral extended pelvic template dissection, depending on previous pelvic treatment and extent/location of nodal disease. Complications were reported using the Clavien-Dindo classification system. Definitions of prostate-specific antigen (PSA) treatment response to RASND were defined as 6-week PSA <0.2 ng/mL (broad definition) or PSA <0.05 ng/mL (strict definition) in those who had undergone primary prostatectomy, and 6-week PSA level < post-radiotherapy nadir in those who had undergone primary radiotherapy. Biochemical recurrence (BCR) after RASND was defined as a PSA >0.2 ng/mL or PSA > nadir, for those who had undergone primary prostatectomy and primary radiotherapy, respectively. Predictors of treatment response were analysed using univariate binary logistic regression. A total of 58 lesions suspicious for lymph node metastases (LNM) in 35 patients were detected on 68 Ga-PSMA imaging. A total of 32 patients (91%) had histopathologically proven LNM at RASND, with a total of 87 LNM and a median (interquartile range) of 2 (1-3) LNM per patient. In all, eight patients (23%) experienced complications, all Clavien-Dindo grade ≤2. Treatment response was seen in 15 (43%) and 11 patients (31%), using the broad and strict definitions, respectively. BCR-free survival and clinical recurrence-free survival at a median follow-up of 12 months were 23% and 66%, respectively, for the entire cohort. Bilateral template dissection was the only significant univariate predictor of treatment response in our cohort. Although RASND appears safe and feasible, less than half of our cohort had a treatment response, and less than a quarter experienced BCR-free survival at 12-month median follow-up. 68 Ga-PSMA imaging underestimates micro-metastatic disease, therefore RASND will rarely be curative. Strict patient selection and restricting RASND to clinical trials is recommended. Long-term follow-up from such trials is required to further assess potential quality of life and mortality benefits. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Low incidence of new biochemical hypogonadism after intensity modulated radiation therapy for prostate cancer.

PubMed

Markovina, Stephanie; Weschenfelder, Débora Cristina; Gay, Hiram; McCandless, Audrey; Carey, Bethany; DeWees, Todd; Knutson, Nels; Michalski, Jeff

2014-01-01

To evaluate serum testosterone and the incidence of biochemical hypogonadism in men treated with intensity modulated radiation therapy (IMRT) for prostate cancer. Serum testosterone was evaluated prospectively in 51 men at pretreatment and at 6-month time points for 2 years posttreatment with IMRT for prostate cancer. Forty-one patients (80%) were treated with definitive intent and 10 patients with postprostatectomy radiation to median total doses of 7380 cGy and 6480 cGy, respectively. No patients received hormone therapy within 12 months of any serum testosterone value. Biochemical hypogonadism was defined as a total serum testosterone level ≤ 300 ng/dL. Incidental testicular dose was calculated using planning software when computed tomography information was available (n = 21) and using a published method of estimation when not available (n = 24), and was available for 45 patients. A statistically significant decrease in testosterone, though small in magnitude, was seen at 6 months after completion of therapy, with no significant difference by 1 year after completion of therapy. There was no increase in biochemical hypogonadism after IMRT. Below-normal pretreatment testosterone was not associated with a transient decrease. Estimated cumulative testicular dose, including dose from daily imaging, was not associated with a change in testosterone, nor was radiation therapy prescription dose or treatment intent (postoperative vs definitive). The mild transient decrease in serum testosterone following IMRT monotherapy for prostate cancer is not associated with new biochemical hypogonadism.

Simultaneous whole-body 18F-PSMA-1007-PET/MRI with integrated high-resolution multiparametric imaging of the prostatic fossa for comprehensive oncological staging of patients with prostate cancer: a pilot study.

PubMed

Freitag, Martin T; Kesch, Claudia; Cardinale, Jens; Flechsig, Paul; Floca, Ralf; Eiber, Matthias; Bonekamp, David; Radtke, Jan P; Kratochwil, Clemens; Kopka, Klaus; Hohenfellner, Markus; Stenzinger, Albrecht; Schlemmer, Heinz-Peter; Haberkorn, Uwe; Giesel, Frederik

2018-03-01

The aim of the present study was to explore the clinical feasibility and reproducibility of a comprehensive whole-body 18 F-PSMA-1007-PET/MRI protocol for imaging prostate cancer (PC) patients. Eight patients with high-risk biopsy-proven PC underwent a whole-body PET/MRI (3 h p.i.) including a multi-parametric prostate MRI after 18 F-PSMA-1007-PET/CT (1 h p.i.) which served as reference. Seven patients presented with non-treated PC, whereas one patient presented with biochemical recurrence. SUV mean -quantification was performed using a 3D-isocontour volume-of-interest. Imaging data was consulted for TNM-staging and compared with histopathology. PC was confirmed in 4/7 patients additionally by histopathology after surgery. PET-artifacts, co-registration of pelvic PET/MRI and MRI-data were assessed (PI-RADS 2.0). The examinations were well accepted by patients and comprised 1 h. SUV mean -values between PET/CT (1 h p.i.) and PET/MRI (3 h p.i.) were significantly correlated (p < 0.0001, respectively) and similar to literature of 18 F-PSMA-1007-PET/CT 1 h vs 3 h p.i. The dominant intraprostatic lesion could be detected in all seven patients in both PET and MRI. T2c, T3a, T3b and T4 features were detected complimentarily by PET and MRI in five patients. PET/MRI demonstrated moderate photopenic PET-artifacts surrounding liver and kidneys representing high-contrast areas, no PET-artifacts were observed for PET/CT. Simultaneous PET-readout during prostate MRI achieved optimal co-registration results. The presented 18 F-PSMA-1007-PET/MRI protocol combines efficient whole-body assessment with high-resolution co-registered PET/MRI of the prostatic fossa for comprehensive oncological staging of patients with PC.

Potential for Higher Treatment Failure in Obese Patients: Correlation of Elevated Body Mass Index and Increased Daily Prostate Deviations From the Radiation Beam Isocenters in an Analysis of 1,465 Computed Tomographic Images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, James R.; Gao Zhanrong; Merrick, Scott

2009-09-01

Purpose: Recent clinical outcome studies on prostate cancer have reported the influence of patient's obesity on the biochemical failure rates after various treatment modalities. In this study, we investigated the effect of patient's physical characteristics on prostate shift in external beam radiotherapy (EBRT) and hypothesized that there maybe a correlation between patient physique and tumor shift. Methods and Materials: A retrospective analysis was performed using data for 117 patients who received image-guided radiation therapy (IGRT) for prostate cancer between January 2005 and April 2007. A total of 1,465 CT scans were analyzed. The standard deviations (SDs) of prostate shifts formore » all patients, along with patient weight, body mass index (BMI), and subcutaneous adipose-tissue thickness (SAT), were determined. Spearman rank correlation analysis was performed. Results: Of the 117 patients, 26.5% were considered normal weight, 48.7% were overweight, 17.9% were mildly obese, and 6.9% were moderately to severely obese. Notably 1.3%, 1.5%, 2.0%, and 21.2% of the respective shifts were greater than 10 mm in the left-right (LR) direction for the four patient groups, whereas in the anterior-posterior direction the shifts are 18.2%, 12.6%, 6.7%, and 21.0%, respectively. Strong correlations were observed between SAT, BMI, patient weight, and SDs of daily shifts in the LR direction (p < 0.01). Conclusions: The strong correlation between obesity and shift indicates that without image-guided radiation therapy, the target volume (prostate with or without seminal vesicles) may not receive the intended dose for patients who are moderate to severely obese. This may explain the higher recurrence rate with conventional external beam radiation therapy.« less

IMPACT OF STAGE MIGRATION AND PRACTICE CHANGES ON HIGH RISK PROSTATE CANCER: RESULTS FROM PATIENTS TREATED WITH RADICAL PROSTATECTOMY OVER THE LAST TWO DECADES

PubMed Central

Fossati, N.; Passoni, N. M.; Moschini, M.; Gandaglia, G.; Larcher, A.; Freschi, M.; Guazzoni, G.; Sjoberg, D. D.; Vickers, A. J.; Montorsi, F.; Briganti, A.

2016-01-01

Background Phenotype of prostate cancer at diagnosis has changed through the years. We aim to evaluate the impact of year of surgery on clinical, pathologic and oncologic outcomes of high-risk prostate cancer patients. Patients and methods We evaluated 1,033 clinically high-risk patients, defined as the presence of at least one of the following risk factors: pre-operative prostate specific antigen (PSA) level >20 ng/ml, and/or clinical stage ≥T3, and/or biopsy Gleason score ≥8. Patients were treated between 1990 and 2013 at a single Institution. Year-per-year trends of clinical and pathologic characteristics were examined. Multivariable Cox regression analysis was used to test the relationship between year of surgery and oncologic outcomes. Results We observed a decrease over time in the proportion of high-risk patients with a pre-operative PSA level >20 ng/ml or clinical stage cT3. An opposite trend was seen for biopsy Gleason score ≥8. We observed a considerable increase in the median number of lymph nodes removed that was associated with an increased rate of LNI. At multivariable Cox regression analysis, year of surgery was associated with a reduced risk of biochemical recurrence (HR per 5-year: 0.90; 95% CI: 0.84–0.96; p=0.01) and distant metastasis (HR per 5-year: 0.91; 95% CI: 0.83–0.99; p=0.039), after adjusting for age, pre-operative PSA, pathologic stage, lymph node invasion, surgical margin status, and pathological Gleason score. Conclusions In this single center study, an increased diagnosis of localized and less extensive high-grade prostate cancer was observed over the last two decades. High-risk patients selected for radical prostatectomy showed better cancer control over time. Better definitions of what constitutes high-risk prostate cancer among contemporary patients are needed. PMID:25787671

Association between preoperative erectile dysfunction and prostate cancer features--an analysis from the Duke Prostate Center Database.

PubMed

Kimura, Masaki; Bañez, Lionel L; Gerber, Leah; Qi, Jim; Tsivian, Matvey; Freedland, Stephen J; Satoh, Takefumi; Polascik, Thomas J; Baba, Shiro; Moul, Judd W

2012-04-01

Erectile dysfunction (ED) is related to several co-morbidities including obesity, metabolic syndrome, cigarette smoking, and low testosterone, all of which have been reported to be associated with adverse prostate cancer features. To examine whether preoperative ED has a relationship with adverse prostate cancer features in patients who underwent radical prostatectomy (RP). We analyzed data from our institution on 676 patients who underwent RP between 2001 and 2010. Crude and adjusted logistic regression models were used to investigate the association between preoperative ED and several pathological parameters. The log-rank test and multivariate proportional hazards model were conducted to determine the association of preoperative ED with biochemical recurrence (BCR). The expanded prostate cancer index composite (EPIC) instrument was used to evaluate preoperative erectile function (EF). Preoperative normal EF was defined as EPIC-SF ≥ 60 points while ED was defined as preoperative EPIC-SF lower than 60 points. Preoperatively, a total of 343 (50.7%) men had normal EF and 333 (49.3%) men had ED. After adjusting for covariates, preoperative ED was identified a risk factor for positive extracapsular extension (OR 1.57; P = 0.029) and high percentage of tumor involvement (OR 1.56; P = 0.047). In a Kaplan-Meier curve, a trend was identified that patients with ED had higher incidence of BCR than men with normal EF (P = 0.091). Moreover, using a multivariate Cox model, higher preoperative EF was negatively associated with BCR (HR 0.99; P = 0.014). These results suggest that the likelihood for adverse pathological outcomes as well as BCR following prostatectomy is higher among men with preoperative ED, though these results require validation in larger datasets. The present study indicates that preoperative ED might be a surrogate for adverse prostate cancer outcomes following RP. © 2011 International Society for Sexual Medicine.

A review of pomegranate in prostate cancer.

PubMed

Paller, C J; Pantuck, A; Carducci, M A

2017-09-01

Preclinical studies showing that pomegranate juice and its components inhibit prostate cancer led to multiple clinical trials to determine whether pomegranate products could slow the growth of prostate cancer. This review summarizes the preclinical data and discusses the results of the clinical trials. Trials targeted patients on active surveillance, neoadjuvant patients, patients with biochemical recurrence (BCR) following local therapy for prostate cancer, and patients with metastatic castration-resistant prostate cancer (mCRPC). In the BCR patient population, early phase II trials of both pomegranate juice and extract showed significant lengthening of PSA doubling time (PSADT), and confirmed the safety of pomegranate products. While a placebo-controlled phase III trial determined that pomegranate extract did not significantly prolong PSADT in BCR patients, a preplanned subset analysis of patients with the manganese superoxide dismutase (MnSOD) AA genotype showed greater PSADT lengthening on the pomegranate extract arm. In the neoadjuvant population, a large trial demonstrated a significant increase in urolithin A and a non-significant reduction in 8-hydroxy-2-deoxyguanosine, a marker of oxidation in prostate cancer tissue, on the pomegranate arm vs the placebo arm. In addition, a randomized clinical trial of a polyphenol-rich multicomponent food supplement that included a 31.25% pomegranate extract found significant slowing of PSA increase in the food supplement arm vs placebo in men on active surveillance and those experiencing BCR. Pomegranate juice and extract are safe but did not significantly improve outcomes in BCR patients in a large placebo-controlled trial. However a subset of BCR patients with the MnSOD AA genotype appear to respond positively to the antioxidant effects of pomegranate treatment. Phase II trials of 100% pomegranate products in neoadjuvant patients and patients with mCRPC were negative. A multicomponent food supplement showed promising results in a phase II study in active surveillance and BCR patients.

Identification and Validation of Potential New Biomarkers for Prostate Cancer Diagnosis and Prognosis Using 2D-DIGE and MS

PubMed Central

Geisler, Cordelia; Gaisa, Nadine T.; Pfister, David; Fuessel, Susanne; Kristiansen, Glen; Braunschweig, Till; Gostek, Sonja; Beine, Birte; Diehl, Hanna C.; Jackson, Angela M.; Borchers, Christoph H.; Heidenreich, Axel; Meyer, Helmut E.; Knüchel, Ruth; Henkel, Corinna

2015-01-01

This study was designed to identify and validate potential new biomarkers for prostate cancer and to distinguish patients with and without biochemical relapse. Prostate tissue samples analyzed by 2D-DIGE (two-dimensional difference in gel electrophoresis) and mass spectrometry (MS) revealed downregulation of secernin-1 (P < 0.044) in prostate cancer, while vinculin showed significant upregulation (P < 0.001). Secernin-1 overexpression in prostate tissue was validated using Western blot and immunohistochemistry while vinculin expression was validated using immunohistochemistry. These findings indicate that secernin-1 and vinculin are potential new tissue biomarkers for prostate cancer diagnosis and prognosis, respectively. For validation, protein levels in urine were also examined by Western blot analysis. Urinary vinculin levels in prostate cancer patients were significantly higher than in urine from nontumor patients (P = 0.006). Using multiple reaction monitoring-MS (MRM-MS) analysis, prostatic acid phosphatase (PAP) showed significant higher levels in the urine of prostate cancer patients compared to controls (P = 0.012), while galectin-3 showed significant lower levels in the urine of prostate cancer patients with biochemical relapse, compared to those without relapse (P = 0.017). Three proteins were successfully differentiated between patients with and without prostate cancer and patients with and without relapse by using MRM. Thus, this technique shows promise for implementation as a noninvasive clinical diagnostic technique. PMID:25667921

Hemato-biochemical alterations and urinalysis in dogs suffering from benign prostatic hyperplasia

PubMed Central

Das, M. R.; Patra, R. C.; Das, R. K.; Rath, P. K.; Mishra, B. P.

2017-01-01

Aim: The study was designed to evaluate the hemato-biochemical alterations, urinalysis along with histomorphological and histological changes of prostate glands in dogs affected with benign prostatic hyperplasia (BPH) in and around Bhubaneswar, Odisha, India. Materials and Methods: In toto, 445 dogs presented to the Teaching Veterinary Clinical Complex of the College of Veterinary Sciences and Animal Husbandry, one Government Veterinary Hospital and two pet clinics in and around Bhubaneswar screened for the presence of BPH. Most of the 57 dogs were 6 years and above as reported by the owners. Only 57 dogs found positive for BPH basing on the presence of typical clinical signs subjected for a detailed hemato-biochemical study. Most of the 57 dogs were 6 years and above as reported by the owners. Routine and microscopic urinalyses were done as per the routine procedure. Histomorphological evaluations of prostate glands were done through manual rectal palpation. Histological examinations of prostate tissue sections of two dead dogs were conducted with routine hematoxylin and eosin stain. Results: The study revealed about 12.8% (57/445) of dogs was suffering from BPH. Typical clinical signs - such as passing small thin tape-shaped feces, holding tail away from backward, tenesmus, and straining during urination and defecation - were seen in most of the cases. Urine samples of affected dogs were positive for glucose, occult blood, and protein. A significant decrease in lymphocytes and increase in eosinophil counts in dogs with BPH was recorded. Serum biochemical analysis showed a nonsignificant increase in creatinine and blood urea nitrogen with a significant decrease in total protein, albumin, globulin, A:G ratio. Histology of prostate glands collected during postmortem was characterized by fibrosis of prostate gland, and hyperplasia of the acinar epithelium. Conclusions: High rate of the prevalence of BPH in dogs poses an alarming condition which if diagnosed at an early stage can certainly prolong the longevity of the dogs. PMID:28435196

The Influence of Prostate Volume on Outcome After High-Dose-Rate Brachytherapy Alone for Localized Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Le, Hien, E-mail: hien.le@health.sa.gov.au; Rojas, Ana; Alonzi, Roberto

2013-10-01

Objective: To determine whether late genitourinary toxicity, biochemical control of prostate cancer, and dosimetric parameters in patients with large prostate glands is different from those variables in men with smaller glands after treatment with high-dose-rate brachytherapy alone (HDR-BT). Methods: From November 2003 to July 2009, 164 patients with locally advanced prostate carcinoma were sequentially enrolled and treated with 34 or 36 Gy in 4 fractions and 31.5 Gy in 3 fractions of {sup 192}Ir HDR-BT alone. The median follow-up time was 71 months. Gland size was not considered in the selection criteria for this study. Estimates of freedom from biochemicalmore » relapse (FFbR) and late morbidity, stratified by median clinical target volume (CTV), were obtained, and differences were compared. Results: The median CTV volume was 60 cc (range, 15-208 cc). Dose–volume parameters D90 and V100 (ie, minimum dose to 90% of the prostate volume and volume receiving 100% of the prescribed isodose) achieved in patients with glands ≥60 cc were not significantly different from those with glands <60 cc (P≥.2). Nonetheless, biochemical control in patients with larger CTV was significantly higher (91% vs 78% at 6 years; P=.004). In univariate and multivariate analysis, CTV was a significant predictor for risk of biochemical relapse. This was not at the expense of an increase in either moderate (P=.6) or severe (P=.3) late genitourinary toxicity. The use of hormonal therapy was 17% lower in the large gland group (P=.01). Conclusions: Prostate gland size does not affect dosimetric parameters in HDR-BT assessed by D90 and V100. In patients with larger glands, a significantly higher biochemical control of disease was observed, with no difference in late toxicity. This improvement cannot be attributed to differences in dosimetry. Gland size should not be considered in the selection of patients for HDR-BT.« less

A Dose–Response Analysis of Biochemical Control Outcomes After {sup 125}I Monotherapy for Patients With Favorable-Risk Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shiraishi, Yutaka, E-mail: shiraishi@rad.med.keio.ac.jp; Department of Radiology, National Hospital Organization Tokyo Medical Center, Tokyo; Yorozu, Atsunori

Purpose: To define the optimal dose for {sup 125}I prostate implants by correlating postimplantation dosimetry findings with biochemical failure and toxicity. Methods and Materials: Between 2003 and 2009, 683 patients with prostate cancer were treated with {sup 125}I prostate brachytherapy without supplemental external beam radiation therapy and were followed up for a median time of 80 months. Implant dose was defined as the D90 (the minimal dose received by 90% of the prostate) on postoperative day 1 and 1 month after implantation. Therefore, 2 dosimetric variables (day 1 D90 and day 30 D90) were analyzed for each patient. We investigated the dosemore » effects on biochemical control and toxicity. Results: The 7-year biochemical failure-free survival (BFFS) rate for the group overall was 96.4% according to the Phoenix definition. A multivariate analysis found day 1 D90 and day 30 D90 to be the most significant factors affecting BFFS. The cutoff points for day 1 D90 and day 30 D90, calculated from ROC curves, were 163 Gy and 175 Gy, respectively. By use of univariate analysis, various dosimetric cutoff points for day 30 D90 were tested. We found that day 30 D90 cutoff points from 130 to 180 Gy appeared to be good for the entire cohort. Greater D90s were associated with an increase in late genitourinary or gastrointestinal toxicity ≥ grade 2, but the increase was not statistically significant. Conclusions: Improvements in BFFS rates were seen with increasing D90 levels. Day 30 D90 doses of 130 to 180 Gy were found to serve as cutoff levels. For low-risk and low-tier intermediate-risk prostate cancer patients, high prostate D90s, even with doses exceeding 180 Gy, achieve better treatment results and are feasible.« less

68Ga-Prostate-Specific Membrane Antigen PET/CT in Triple-Negative Breast Cancer.

PubMed

Passah, Averilicia; Arora, Saurabh; Damle, Nishikant Avinash; Tripathi, Madhavi; Bal, Chandrasekhar; Subudhi, T Kishan; Arora, Geetanjali

2018-06-01

The prostate-specific membrane antigen (PSMA) is a transmembrane protein with elevated expression in prostate cancer cells. Breast cancer also shows PSMA expression. We present the case of a 30-year-old woman with triple-negative bilateral breast carcinoma who underwent bilateral mastectomy, chemotherapy, and radiotherapy. She developed a left chest wall and liver recurrence after primary therapy. Her recurrent disease was also triple-negative. In view of the known poor prognosis and very limited therapeutic options, we performed Ga-PSMA PET/CT scan to explore the possibility of PSMA-based therapy as a future option after exhausting standard-of-care treatments.

Gleason score at diagnosis predicts the rate of detection of 18F-choline PET/CT performed when biochemical evidence indicates recurrence of prostate cancer: experience with 1,000 patients.

PubMed

Cimitan, Marino; Evangelista, Laura; Hodolič, Marina; Mariani, Giuliano; Baseric, Tanja; Bodanza, Valentina; Saladini, Giorgio; Volterrani, Duccio; Cervino, Anna Rita; Gregianin, Michele; Puccini, Giulia; Guidoccio, Federica; Fettich, Jure; Borsatti, Eugenio

2015-02-01

The objective of this study was to explore the ability of the initial Gleason score (GS) to predict the rate of detection of recurrent prostate cancer (PCa) with (18)F-choline PET/CT in a large cohort of patients. Data from 1,000 patients who had undergone (18)F-choline PET/CT because of biochemical evidence of relapse of PCa between 2004 and 2013 were retrieved from databases at 4 centers. Continuous data were compared by the Student t test or ANOVA, and categoric variables were compared by the χ(2) test. Univariable and multivariable analyses were performed by logistic regression. The GS at diagnosis was less than or equal to 6 in 257 patients, 7 in 347 patients, and greater than 7 in 396 patients. The results of 645 PET/CT scans were positive for PCa recurrence. Eighty-one percent of the positive PET/CT results were found in patients with a PSA level of greater than or equal to 2 ng/mL, 43% were found in patients with a PSA level of 1-2 ng/mL, and 31% were found in patients with a PSA level of less than or equal to 1 ng/mL; 78.8% of patients with positive PET/CT results had a GS of greater than 7. The results of (18)F-choline PET/CT scans were negative in 300 patients; 44% had a GS of less than or equal to 6, 35% had a GS of 7, and 17% had a GS of greater than 7. PET/CT results were rated as doubtful in only 5.5% of patients (median PSA, 1.8 ng/mL). When the GS was greater than 7, the rates of detection of (18)F-choline PET/CT were 51%, 65%, and 91% for a PSA level of less than 1 ng/mL, 1-2 ng/mL, and greater than 2 ng/mL, respectively. In univariable and multivariable analyses, both a GS of 7 and a GS of greater than 7 were independent predictors for positive (18)F-choline PET/CT results (odds ratios, 0.226 and 0.330, respectively; P values for both, <0.001). A high GS at diagnosis is a strong predictive factor for positive (18)F-choline PET/CT scan results for recurrent PCa, even when the PSA level is low (i.e., ≤1 ng/mL). © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Nc886 is epigenetically repressed in prostate cancer and acts as a tumor suppressor through the inhibition of cell growth.

PubMed

Fort, Rafael Sebastián; Mathó, Cecilia; Geraldo, Murilo Vieira; Ottati, María Carolina; Yamashita, Alex Shimura; Saito, Kelly Cristina; Leite, Katia Ramos Moreira; Méndez, Manuel; Maedo, Noemí; Méndez, Laura; Garat, Beatriz; Kimura, Edna Teruko; Sotelo-Silveira, José Roberto; Duhagon, María Ana

2018-02-02

Nc886 is a 102 bp non-coding RNA transcript initially classified as a microRNA precursor (Pre-miR-886), later as a divergent homologue of the vault RNAs (vtRNA 2-1) and more recently as a novel type of RNA (nc886). Although nc886/vtRNA2-1/Pre-miR-886 identity is still controversial, it was shown to be epigenetically controlled, presenting both tumor suppressor and oncogenic function in different cancers. Here, we study for the first time the role of nc886 in prostate cancer. Nc886 promoter methylation status and its correlation with patient clinical parameters or DNMTs levels were evaluated in TCGA and specific GEO prostate tissue datasets. Nc886 level was measured by RT-qPCR to compare normal/neoplastic prostate cells from radical prostatectomies and cell lines, and to assess nc886 response to demethylating agents. The effect of nc886 recovery in cell proliferation (in vitro and in vivo) and invasion (in vitro) was evaluated using lentiviral transduced DU145 and LNCaP cell lines. The association between the expression of nc886 and selected genes was analyzed in the TCGA-PRAD cohort. Nc886 promoter methylation increases in tumor vs. normal prostate tissue, as well as in metastatic vs. normal prostate tissue. Additionally, nc886 promoter methylation correlates with prostate cancer clinical staging, including biochemical recurrence, Clinical T-value and Gleason score. Nc886 transcript is downregulated in tumor vs. normal tissue -in agreement with its promoter methylation status- and increases upon demethylating treatment. In functional studies, the overexpression of nc886 in the LNCaP and DU145 cell line leads to a decreased in vitro cell proliferation and invasion, as well as a reduced in vivo cell growth in NUDE-mice tumor xenografts. Finally, nc886 expression associates with the prostate cancer cell cycle progression gene signature in TCGA-PRAD. Our data suggest a tumor suppressor role for nc886 in the prostate, whose expression is epigenetically silenced in cancer leading to an increase in cell proliferation and invasion. Nc886 might hold clinical value in prostate cancer due to its association with clinical parameters and with a clinically validated gene signature.

SRD5A polymorphisms and biochemical failure after radical prostatectomy.

PubMed

Audet-Walsh, Etienne; Bellemare, Judith; Nadeau, Geneviève; Lacombe, Louis; Fradet, Yves; Fradet, Vincent; Huang, Shu-Pin; Bao, Bo-Ying; Douville, Pierre; Girard, Hugo; Guillemette, Chantal; Lévesque, Eric

2011-12-01

The relationship between inherited germ-line variations in the 5α-reductase pathways of androgen biosynthesis and the risk of biochemical recurrence (BCR) after radical prostatectomy (RP) remains an unexplored area. To determine the link between germ-line variations in the steroid-5α-reductase, α-polypeptide 1 (SRD5A1) and steroid-5α-reductase, α-polypeptide 2 (SRD5A2) genes and BCR. We studied retrospectively two independent cohorts composed of 526 white (25% BCR) and 320 Asian men (36% BCR) with pathologically organ-confined prostate cancer who had a median follow-up of 88.8 and 30.8 mo after surgery, respectively. Patients were genotyped for 19 haplotype-tagging single nucleotide polymorphisms (htSNPs) in SRD5A1 and SRD5A2 genes, and their prognostic significance on prostate-specific antigen recurrence was assessed using Kaplan-Meier analysis and the Cox regression model. After adjusting for all clinicopathologic risk factors, four SNPs (rs2208532, rs12470143, rs523349, and rs4952197) were associated with BCR in both whites and Asians. The strongest effect was conferred by the SRD5A2 V89L nonsynonymous SNP (rs523349C) with a hazard ratio (HR) of 2.87 (95% confidence interval [CI], 2.07-4.00; p = 4 × 10⁻¹⁰; 48% BCR). In addition, in whites, the combination of two SNPs, rs518673T in SRD5A1 and rs12470143A in SRD5A2, was associated with a reduced BCR rate for carriers of three or four alleles (HR: 0.37; 95% CI, 0.19-0.71; p=0.003;16% BCR) compared with noncarriers (38% BCR), whereas the SRD5A2 rs12470143A was significant in Asians (HR: 0.46; 95% CI, 0.28-0.73; p=0.001). Limitations of our study include few events of androgen-deprivation resistance or cancer-specific death. Our study is the first to show positive associations of several SRD5A1 and SRD5A2 variations as independent predictors of BCR after RP. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

PET/CT with (18)F-choline after radical prostatectomy in patients with PSA ≤2 ng/ml. Can PSA velocity and PSA doubling time help in patient selection?

PubMed

Chiaravalloti, Agostino; Di Biagio, Daniele; Tavolozza, Mario; Calabria, Ferdinando; Schillaci, Orazio

2016-07-01

To investigate the performance of (18)F-fluorocholine ((18)F-FCH) PET/CT in relation to the prostate-specific antigen (PSA) kinetic indexes, PSA doubling time (PSAdt) and PSA velocity (PSAve), in detecting recurrent prostate cancer (PC) in a selected population of patients treated with radical prostatectomy and with PSA ≤2 ng/ml. The study group comprised 79 patients (mean age 70 ± 7 years, range 58 - 77 years) who had been treated with radical surgery 30 to 90 months previously and with biochemical failure (defined as a measurable serum PSA level) who were evaluated with (18)F-FCH PET/CT. In order to establish the optimal threshold for PSAdt and PSAve, the diagnostic performance of PSA, PSAdt and PSAve were compared by receiver operating characteristic analysis. In the population examined, PSA (mean ± SD) was 1.37 ± 0.44 ng/ml (range 0.21 - 2 ng/ml) before PET/CT examination, PSAdt was 10.04 ± 16.67 months and PSAve was 2.75 ± 3.11 ng/ml per year. (18)F-FCH PET/CT was positive in 44 patients (55 %). PSAve and PSAdt were significantly different between patients with a positive and a negative (18)F-FCH PET/CT scan. Thresholds of 6 months for PSAdt and 1 ng/ml per year for PSAve were selected. For PSAdt ≤6 months the detection rate (DR) was 65 %, and for PSAve >1 ng/ml per year the DR was 67 %. PSA values were not significantly different between patients with a positive and a negative PET/CT scan. The results of our study suggest that (18)F-FCH PET/CT could be considered for the evaluation of patients with biochemical recurrence of PC and with low PSA levels. Fast PSA kinetics could be useful in the selection of these patients.

Investigating the role of the IGF axis as a predictor of biochemical recurrence in prostate cancer patients post-surgery.

PubMed

Breen, Kieran J; O'Neill, Amanda; Murphy, Lisa; Fan, Yue; Boyce, Susie; Fitzgerald, Noel; Dorris, Emma; Brady, Lauren; Finn, Stephen P; Hayes, Brian D; Treacy, Ann; Barrett, Ciara; Aziz, Mardiana Abdul; Kay, Elaine W; Fitzpatrick, John M; Watson, R William G

2017-09-01

Between 20% and 35% of prostate cancer (PCa) patients who undergo treatment with curative intent (ie, surgery or radiation therapy) for localized disease will experience biochemical recurrence (BCR). Alterations in the insulin-like growth factor (IGF) axis and PTEN expression have been implicated in the development and progression of several human tumors including PCa. We examined the expression of the insulin receptor (INSR), IGF-1 receptor (IGF-1R), PTEN, and AKT in radical prostatectomy tissue of patients who developed BCR post-surgery. Tissue microarrays (TMA) of 130 patients post-radical prostatectomy (65 = BCR, 65 = non-BCR) were stained by immunohistochemistry for INSR, IGF-1R, PTEN, and AKT using optimized antibody protocols. INSR, IGF1-R, PTEN, and AKT expression between benign and cancerous tissue, and different Gleason grades was assessed. Kaplan-Meier survival curves were used to examine the relationship between proteins expression and BCR. INSR (P < 0.001), IGF-1R (P < 0.001), and AKT (P < 0.05) expression was significantly increased and PTEN (P < 0.001) was significantly decreased in cancerous versus benign tissue. There was no significant difference in INSR, IGF-1R, or AKT expression in the cancerous tissue of non-BCR versus BCR patients (P = 0.149, P = 0.990, P = 0.399, respectively). There was a significant decrease in PTEN expression in the malignant tissue of BCR versus non-BCR patients (P = 0.011). Combinational analysis of the tissue proteins identified a combination of decreased PTEN and increased AKT or increased INSR was associated with worst outcome. We found that in each case, our hypothesized worst group was most likely to experience BCR and this was significant for combinations of PTEN+INSR and PTEN+AKT but not PTEN+IGF-1R (P = 0.023, P = 0.028, P = 0.078, respectively). Low PTEN is associated with BCR and this association is strongly modified by high INSR and high AKT expression. Measurement of these proteins could help inform appropriate patient selection for postoperative adjuvant therapy and prevent BCR. © 2017 Wiley Periodicals, Inc.

Up-Regulation of Follistatin-Like 1 By the Androgen Receptor and Melanoma Antigen-A11 in Prostate Cancer.

PubMed

Su, Shifeng; Parris, Amanda B; Grossman, Gail; Mohler, James L; Wang, Zengjun; Wilson, Elizabeth M

2017-04-01

High affinity androgen binding to the androgen receptor (AR) activates genes required for male sex differentiation and promotes the development and progression of prostate cancer. Human AR transcriptional activity involves interactions with coregulatory proteins that include primate-specific melanoma antigen-A11 (MAGE-A11), a coactivator that increases AR transcriptional activity during prostate cancer progression to castration-resistant/recurrent prostate cancer (CRPC). Microarray analysis and quantitative RT-PCR were performed to identify androgen-regulated MAGE-A11-dependent genes in LAPC-4 prostate cancer cells after lentivirus shRNA knockdown of MAGE-A11. Chromatin immunoprecipitation was used to assess androgen-dependent AR recruitment, and immunocytochemistry to localize an androgen-dependent protein in prostate cancer cells and tissue and in the CWR22 human prostate cancer xenograft. Microarray analysis of androgen-treated LAPC-4 prostate cancer cells indicated follistatin-like 1 (FSTL1) is up-regulated by MAGE-A11. Androgen-dependent up-regulation of FSTL1 was inhibited in LAPC-4 cells by lentivirus shRNA knockdown of AR or MAGE-A11. Chromatin immunoprecipitation demonstrated AR recruitment to intron 10 of the FSTL1 gene that contains a classical consensus androgen response element. Increased levels of FSTL1 protein in LAPC-4 cells correlated with higher levels of MAGE-A11 relative to other prostate cancer cells. FSTL1 mRNA levels increased in CRPC and castration-recurrent CWR22 xenografts in association with predominantly nuclear FSTL1. Increased nuclear localization of FSTL1 in prostate cancer was suggested by predominantly cytoplasmic FSTL1 in benign prostate epithelial cells and predominantly nuclear FSTL1 in epithelial cells in CRPC tissue and the castration-recurrent CWR22 xenograft. AR expression studies showed nuclear colocalization of AR and endogenous FSTL1 in response to androgen. AR and MAGE-A11 cooperate in the up-regulation of FSTL1 to promote growth and progression of CRPC. Prostate 77:505-516, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Cell Penetrating Bispecific Antibodies for Targeting Oncogenic Transcription Factors in Advanced Prostate Cancer

DTIC Science & Technology

2016-12-01

biochemical and biologic assay systems. The final specific aim was tol examine the ability of the bispecific antibody to perturb the growth of prostate ...designated by other documentation. TITLE: Cell-Penetrating Bispecific Antibodies for Targeting Oncogenic Transcription Factors in Advanced Prostate ...Bispecific Antibodies for Targeting Oncogenic Transcription Factors in Advanced Prostate Cancer Michael Lilly, MD Richard Weisbart, MD Medical

[Comparative oncologic and functional outcomes of prostate cancer surgery with other curative treatments].

PubMed

Soulié, M; Salomon, L

2015-11-01

Review of the comparative results of different treatment strategies (surgery, radiotherapy, ultrasound, surveillance) of prostate cancer, in which the main goal is the local control and the second target is the tolerance of the side effects of those treatments. Review of literature using Medline databases selected based on scientific relevance. Clinical keys centered on the oncological and functional outcomes of comparative series between different curative treatments. The numerous comparative series between surgery and other therapeutic modalities are essentially retrospective with significant methodological bias that is difficult to overcome in order to formulate the optimal thesis. However, there is a clear tendency toward surgery usually with young patients who have intermediate risk tumors without important comorbidity. In the absence of randomized comparative series with significant power, the oncological and functional results of the radical prostatectomy with or without adjuvant treatment seem at least the same, in a selected population of patients, compared with the combination of radiotherapy-hormonotherapy in terms of survival, without biochemical recurrence, disease-specific survival and overall survival, for the aggressive tumors necessitating curative local treatments. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer

DTIC Science & Technology

2012-09-01

micrometastases that may be targeted with radioimmunotherapy. Prostate specific membrane antigen (PSMA) is the single, most well-established, highly restricted...Radiolabeled anti- prostate specific membrane antigen (PSMA) monoclonal antibody J591 (177Lu-J591) for nonmetastatic castration-resistant prostate cancer...rationale for systemic salvage targeted anti- prostate specific membrane antigen radioimmunotherapy. Adv Urol 2012, Article ID 921674, doi:10.1155

Contrasting roles of the ABCG2 Q141K variant in prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sobek, Kathryn M.; Cummings, Jessica L.; Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA

ABCG2 is a membrane transport protein that effluxes growth-promoting molecules, such as folates and dihydrotestosterone, as well as chemotherapeutic agents. Therefore it is important to determine how variants of ABCG2 affect the transporter function in order to determine whether modified treatment regimens may be necessary for patients harboring ABCG2 variants. Previous studies have demonstrated an association between the ABCG2 Q141K variant and overall survival after a prostate cancer diagnosis. We report here that in patients with recurrent prostate cancer, those who carry the ABCG2 Q141K variant had a significantly shorter time to PSA recurrence post-prostatectomy than patients homozygous for wild-typemore » ABCG2 (P=0.01). Transport studies showed that wild-type ABCG2 was able to efflux more folic acid than the Q141K variant (P<0.002), suggesting that retained tumoral folate contributes to the decreased time to PSA recurrence in the Q141K variant patients. In a seemingly conflicting study, it was previously reported that docetaxel-treated Q141K variant prostate cancer patients have a longer survival time. We found this may be due to less efficient docetaxel efflux in cells with the Q141K variant versus wild-type ABCG2. In human prostate cancer tissues, confocal microscopy revealed that all genotypes had a mixture of cytoplasmic and plasma membrane staining, with noticeably less staining in the two homozygous KK patients. In conclusion, the Q141K variant plays contrasting roles in prostate cancer: 1) by decreasing folate efflux, increased intracellular folate levels result in enhanced tumor cell proliferation and therefore time to recurrence decreases; and 2) in patients treated with docetaxel, by decreasing its efflux, intratumoral docetaxel levels and tumor cell drug sensitivity increase and therefore patient survival time increases. Taken together, these data suggest that a patient's ABCG2 genotype may be important when determining a personalized treatment plan. - Highlights: • The presence of ABCG2 Q141K variant decreases time to PSA recurrence. • Cells expressing the Q141K variant retain more folic acid than wild type. • Cells expressing the Q141K variant are more sensitive to docetaxel. • ABCG2 protein is repressed miR-519c and/or miR-520h in prostate cancer cell lines.« less

Onion and garlic extracts as potential antidotes for cadmium-induced biochemical alterations in prostate glands of rats.

PubMed

Ola-Mudathir, F K; Suru, S M

2015-11-01

Cadmium (Cd) has been implicated in increased prostate gland malignancy risk in both wildlife and humans. This study examines the chemoprotective roles of onion and garlic extracts on Cd-induced biochemical alterations in the prostate glands of rats. Adult male Wistar rats were randomly divided into nine groups: control group received double distilled water; Cd group received Cd alone (1.5 mg/100 g bwt per day); extract-treated groups were pre-treated with varied doses of onion and/or garlic extract (0.5 ml and 1.0 ml/100 g bwt per day) for 1 week and then co-treated with Cd (1.5 mg/100 g bwt per day) for additional 3 weeks. Oxidant/antioxidant status and acid phosphatase (ACPtotal and ACPprostatic ) activity were examined in prostate glands. Cd intoxication caused a marked (P < 0.001) increase in lipid peroxidation (LPO) and glutathione S-transferase (GST) levels, whereas glutathione (GSH), superoxide dismutase and catalase levels were markedly (P < 0.001) decreased. We also observed significant (P < 0.001) decrease in ACPtotal and ACPprostatic activities in prostate glands and a concomitant significant (P < 0.001) increase in the plasma. However, treatment of Cd-intoxicated rats with onion and/or garlic extract significantly minimised these alterations. The onion extract offered a dose-dependent protection. Our findings suggest a chemoprotective capability for onion and garlic extracts against Cd-induced biochemical alteration in the prostate glands. © 2014 Blackwell Verlag GmbH.

Upper tract urothelial recurrence following radical cystectomy for transitional cell carcinoma of the bladder: an analysis of 1,069 patients with 10-year followup.

PubMed

Sanderson, Kristin M; Cai, Jie; Miranda, Gustavo; Skinner, Donald G; Stein, John P

2007-06-01

Risk factors for upper tract recurrence following radical cystectomy for transitional cell carcinoma of the bladder are not yet well-defined. We reviewed our population of patients who underwent radical cystectomy to identify prognostic factors and clinical outcomes associated with upper tract recurrence. From our prospective database of 1,359 patients who underwent radical cystectomy we identified 1,069 patients treated for transitional cell carcinoma of the bladder between January 1985 and December 2001. Univariate analysis was completed to determine factors predictive of upper tract recurrence. A total of 853 men and 216 women were followed for a median of 10.3 years (maximum 18.5). There were 27 (2.5%) upper tract recurrences diagnosed at a median of 3.3 years (range 0.4 to 9.3). Only urethral tumor involvement was predictive of upper tract recurrence. In men superficial transitional cell carcinoma of the prostatic urethra was associated with an increased risk of upper tract recurrence compared with prostatic stromal invasion or absence of prostatic transitional cell carcinoma (p <0.01). In women urethral transitional cell carcinoma was associated with an increased risk of upper tract recurrence (p = 0.01). Despite routine surveillance 78% of upper tract recurrence was detected after development of symptoms. Median survival following upper tract recurrence was 1.7 years (range 0.2 to 8.8). Detection of asymptomatic upper tract recurrence via surveillance did not predict lower nephroureterectomy tumor stage, absence of lymph node metastases or improved survival. Patients with bladder cancer are at lifelong risk for late oncological recurrence in the upper tract urothelium. Patients with evidence of tumor involvement within the urethra are at highest risk. Surveillance regimens frequently fail to detect tumors before symptoms develop. However, radical nephroureterectomy can provide prolonged survival.

A Prospective Trial of Intensity Modulated Radiation Therapy (IMRT) Incorporating a Simultaneous Integrated Boost for Prostate Cancer: Long-term Outcomes Compared With Standard Image Guided IMRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schild, Michael H.; Schild, Steven E., E-mail: sschild@mayo.edu; Wong, William W.

Purpose: This report describes the long-term outcomes of a prospective trial of intensity modulated radiation therapy (IMRT), integrating a {sup 111}In capromab pendetide (ProstaScint) scan-directed simultaneous integrated boost (SIB) for localized prostate cancer. Methods and Materials: Seventy-one patients with T1N0M0 to T4N0M0 prostate cancer were enrolled, and their ProstaScint and pelvic computed tomography scans were coregistered for treatment planning. The entire prostate received 75.6 Gy in 42 fractions with IMRT, whereas regions of increased uptake on ProstaScint scans received 82 Gy as an SIB. Patients with intermediate- and high-risk disease also received 6 months and 12 months of adjuvant hormonal therapy, respectively. Results: The studymore » enrolled 31 low-, 30 intermediate-, and 10 high-risk patients. The median follow-up was 120 months (range, 24-150 months). The 10-year biochemical control rates were 85% for the entire cohort and 84%, 84%, and 90% for patients with low-, intermediate-, and high-risk disease, respectively. The 10-year survival rate of the entire cohort was 69%. Pretreatment prostate-specific antigen level >10 ng/mL and boost volume of >10% of the prostate volume were significantly associated with poorer biochemical control and survival. The outcomes were compared with those of a cohort of 302 patients treated similarly but without the SIB and followed up for a median of 91 months (range, 6-138 months). The 5- and 10-year biochemical control rates were 86% and 61%, respectively, in patients without the SIB compared with 94% and 85%, respectively, in patients in this trial who received the SIB (P=.02). The cohort that received an SIB did not have increased toxicity. Conclusions: The described IMRT strategy, integrating multiple imaging modalities to administer 75.6 Gy to the entire prostate with a boost dose of 82 Gy, was feasible. The addition of the SIB was associated with greater biochemical control but not toxicity. Modern imaging technology can be used to locally intensify the dose to tumors and spare normal tissues, producing very favorable long-term biochemical disease control.« less

Prognostic Importance of Small Prostate Size in Men Receiving Definitive Prostate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taira, Al V.; Merrick, Gregory S., E-mail: gmerrick@urologicresearchinstitute.org; Galbreath, Robert W.

Purpose: To assess whether small prostate size is an adverse prognostic factor in men undergoing brachytherapy in the same manner in which it seems to be for men undergoing radical prostatectomy. Methods and Materials: From April 1995 to June 2008, 2024 patients underwent brachytherapy by a single brachytherapist. Median follow-up was 7.4 years. The role of small prostate size ({<=}20 cm{sup 3}) as a prognostic factor for biochemical progression-free survival, cause-specific survival, and all-cause mortality was investigated. The differences in survival between men with small and larger prostates were compared using Kaplan-Meier curves and log-rank tests. Results: Median prostate sizemore » for the entire cohort was 32.7 cm{sup 3}. For the 167 men with small prostates, median prostate size was 17.4 cm{sup 3}. There was no difference in biochemical progression-free survival (95.2% vs 96.2%, P=.603), cause-specific survival (97.7% vs 98.3%, P=.546), or all-cause mortality (78.0% vs 77.2%, P=.838) at 10 years for men with small prostates compared with men with larger prostates. On univariate and multivariate analysis, small prostate size was not associated with any of the primary outcome measures. Conclusion: Men with small prostates treated with brachytherapy have excellent outcomes and are at no higher risk of treatment failure than men with larger glands. High-quality implants with adequate margins seem sufficient to address the increased adverse risk factors associated with small prostate size.« less

Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer.

PubMed

Martinez, Alvaro A; Gustafson, Gary; Gonzalez, José; Armour, Elwood; Mitchell, Chris; Edmundson, Gregory; Spencer, William; Stromberg, Jannifer; Huang, Raywin; Vicini, Frank

2002-06-01

To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level >or=10.0 ng/mL, Gleason score >or=7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose <93 Gy (58 patients) and high-dose biologically effective dose >93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p <0.001). Improvement occurred in the cause-specific survival in favor of the brachytherapy high-dose level (p = 0.014). On multivariate analysis, a low-dose level, higher Gleason score, and higher nadir value were associated with increased biochemical failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause-specific survival with higher doses. These results, coupled with the low risk of complications, the advantage of not being radioactive after implantation, and the real-time interactive planning, define a new standard for treatment.

Recurrent Medullary Thyroid Carcinoma on 68Ga-Prostate-Specific Membrane Antigen PET/CT: Exploring New Theranostic Avenues.

PubMed

Arora, Saurabh; Damle, Nishikant Avinash; Parida, Girish Kumar; Singhal, Abhinav; Nalli, Harish; Dattagupta, Shreya; Bal, Chandrasekar

2018-05-01

The prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells. Few other malignancies have shown expression of PSMA. We present a case of 35-year-old man with medullary thyroid carcinoma, post total thyroidectomy and bilateral neck dissection, now presenting with rising calcitonin levels (doubling time 9 months) and local neck recurrence with negative I-MIBG scan. We decided to perform Ga-PSMA-HBED-CC PET/CT scan to assess PSMA expression and explore the therapeutic option in view of rising serum calcitonin. It revealed intense PSMA uptake in the soft tissue mass in left thyroid bed and cervical lymph nodes.

Long-Term Results of a Phase II Trial of Ultrasound-Guided Radioactive Implantation of the Prostate for Definitive Management of Localized Adenocarcinoma of the Prostate (RTOG 98-05)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lawton, Colleen A., E-mail: clawton@mcw.edu; Hunt, Daniel; Lee, W. Robert

2011-09-01

Purpose: To evaluate the long-term effectiveness of transrectal ultrasound-guided permanent radioactive I{sup 125} implantation of the prostate for organ confined adenocarcinoma of the prostate compared with historical data of prostatectomy and external beam radiotherapy within a cooperative group setting. Methods and Materials: Patients accrued to this study had histologically confirmed, locally confined adenocarcinoma of the prostate clinical stage T1b, T1c, or T2a; no nodal or metastatic disease; prostate-specific antigen level of {<=}10 ng/ml; and a Gleason score of {<=}6. All patients underwent transrectal ultrasound-guided radioactive I{sup 125} seed implantation into the prostate. The prescribed dose was 145 Gy to themore » prostate planning target volume. Results: A total of 101 patients from 27 institutions were accrued to this protocol; by design, no single institution accrued more than 8 patients. There were 94 eligible patients. The median follow up was 8.1 years (range, 0.1-9.2 years). After 8 years, 8 patients had protocol-defined biochemical (prostate-specific antigen) failure (cumulative incidence, 8.0%); 5 patients had local failure (cumulative incidence, 5.5%); and 1 patient had distant failure (cumulative incidence, 1.1%; this patient also had biochemical failure and died of causes not related to prostate cancer). The 8-year overall survival rate was 88%. At last follow-up, no patient had died of prostate cancer or related toxicities. Three patients had maximum late toxicities of Grade 3, all of which were genitourinary. No Grade 4 or 5 toxicities were observed. Conclusions: The long-term results of this clinical trial have demonstrated that this kind of trial can be successfully completed through the RTOG and that results in terms of biochemical failure and toxicity compare very favorably with other brachytherapy published series as well as surgical and external beam radiotherapy series. In addition, the prospective, multicenter design highlights the probable generalizability of the outcomes.« less

A Multiplex Cancer/Testis Antigen-Based Biomarker Panel to Predict the Aggressive Phenotype of Prostate Cancer

DTIC Science & Technology

2016-09-01

US (Siegel et al., 2014). The introduction of the prostate specific antigen ( PSA ) test has greatly aided to the early detection of PCa. Detectable...levels of PSA are the earliest sign of recurrent disease after radical prostatectomy (RP) (Pound et al., 1999). Besides its sensitiveness, it is...estimated that 23-44% of patients submitted to RP will progress with detectable PSA levels and will never present recurrence (Draisma et al., 2009). Thus

Small-cell neuroendocrine carcinoma as a variant form of prostate cancer recurrence: a case report and short literature review.

PubMed

Yashi, Masahiro; Terauchi, Fumihito; Nukui, Akinori; Ochi, Masanori; Yuzawa, Masayuki; Hara, Yosuke; Morita, Tatsuo

2006-01-01

Small-cell neuroendocrine carcinoma has been recognized as a rare histologic variant occurring in only 0.5% to 2% of prostatic primary tumors. However, recent autopsy studies suggest development to this phenotype in up to 10% to 20% of the cases with hormone-refractory disease. A case of conventional adenocarcinoma before androgen-ablation therapy but showing progression to small-cell neuroendocrine carcinoma at the recurrence. The immunohistochemistry of the tumor showed strong positive staining for progastrin-releasing peptide (ProGRP), a carboxy terminal region common to 3 precursors for gastrin-releasing peptide, but almost negative staining for chromogranin-A and prostate-specific antigen. Combination chemotherapy based on cisplatin and etoposide was effective for controlling the tumor progression for 7 months, and the serum ProGRP level correlated well to the clinical course. Neither objective nor subjective responses were observed to somatostatin analogue therapy performed in the late stage of disease. The present case reminds the urologist that small-cell neuroendocrine carcinoma may be a variant form of disease recurrence during androgen ablation in advanced prostate cancer. A strategic approach for this phenotype evaluating serum neuroendocrine markers, such as ProGRP, should be taken when serum prostate-specific antigen does not reflect the disease state. This approach would allow one to choose alternative therapies targeting neuroendocrine cells other than androgen ablation.

Radiotherapy in cT3 prostatic carcinoma: retrospective comparison between neoadjuvant and adjuvant hormonotherapy.

PubMed

Cellini, Numa; Luzi, Stefano; Morganti, Alessio Giuseppe; Valentini, Vincenzo; Mantini, Giovanna; Racioppi, Marco; Smaniotto, Daniela; Leone, Mariavittoria; Mattiucci, Gian Carlo; Digesù, Cinzia; Giustacchini, Mario; Destito, Antonio; Alcini, Eugenio

2004-01-01

The aim of this study was to retrospectively compare the clinical outcomes achieved in 2 groups of patients with cT3 prostatic carcinoma undergoing neoadjuvant hormonotherapy and neoadjuvant hormonotherapy plus adjuvant hormonotherapy with external beam radiotherapy. One hundred patients with cT3N0M0 prostatic carcinoma underwent radiotherapy to pelvic lymph nodes (45 Gy, 1.8 Gy/fraction) with a booster dose (65-70 Gy) to the prostatic cavity. Forty-four patients received neoadjuvant hormonotherapy (goserelin, starting 2 months before radiotherapy and continuing until the end of irradiation); 56 patients received neoadjuvant hormonotherapy plus adjuvant goserelin until disease progression, if present. Patients undergoing adjuvant hormonotherapy as compared to those who received exclusive neoadjuvant therapy showed a higher reduction in PSA level below 1.0 ng/ml (p = 0.0211), a lower incidence of biochemical failures (p = 0.0170), a lower incidence of hematogenous metastases (p = 0.0320) and a trend suggestive of a better disease-free survival (p = 0.0660). At univariate analysis (logrank), Gleason score did not show a significant correlation with any of the end points analyzed. To the contrary, patients with tumor <15 mm showed a better local control (p = 0.0347) and biochemical failure-free survival (p = 0.0102). Furthermore, a trend between initial PSA level and incidence of hematogenous metastases was observed (p = 0.0519). Patients with a posttreatment PSA level <1.0 ng/ml had a lower incidence of metastases (p = 0.0237) and a better survival (p = 0.0178); patients with complete clinical response showed a lower incidence of biochemical failures (p = 0.0469). Radiotherapy doses >70 Gy showed a trend with biochemical failure-free survival (p = 0.0554). At multivariate analysis, a correlation between Gleason score and incidence of metastases (p = 0.0232), and between tumor diameter and local control (p = 0.0178) and biochemical failure-free survival (p = 0.0290) was recorded. In patients with cT3N0M0 prostate carcinoma, prolonged hormonotherapy was shown to be significantly correlated with biochemical failure-free survival and distant metastasis-free survival. Furthermore, tumor size had a significant impact on biochemical failure-free survival as well as on local control. Copyright 2004 S. Karger AG, Basel

Robotic radical prostatectomy in patients with high-risk disease: a review of short-term outcomes from a high-volume center.

PubMed

Jayram, Gautam; Decastro, Guarionex J; Large, Michael C; Razmaria, Aria; Zagaja, Gregory P; Shalhav, Arieh L; Brendler, Charles B

2011-03-01

Patients with high-risk prostate cancer have historically been treated with multimodal therapy and considered poor candidates for minimally invasive surgery. We reviewed our experiences with robot-assisted radical prostatectomy (RARP) in patients with high-risk clinical features. Clinical database review identified high-risk patients undergoing RARP by two high-volume robotic surgeons. D'Amico's criteria for high-risk prostate cancer were utilized: prostate-specific antigen ≥ 20 ng/mL, clinical stage ≥ T2c, or preoperative Gleason grade ≥ 8. About 148 patients were identified in the study group. Mean age at surgery was 60.9 years, and mean body mass index was 27.9. Mean estimated blood loss was 150 cc and the transfusion rate was 2.7%. Median hospital stay was 1 day and the rate of major complications (Clavien grade ≥ 3) was 3.4%. Bilateral nerve preservation was feasible in 28.4%, and the rate of positive surgical margins was 20.9%. Final pathology demonstrated extra-capsular disease in 54.1% of patients and 12.3% had lymph node involvement. At 2 years of follow-up, 21.3% of patients had experienced biochemical recurrence or had persistent disease after treatment. Continence was 91.2% (1 pad or less) and total impotence (inability to masturbate) was 48.3%. RARP does not compromise oncologic or functional outcomes in patients with high-risk prostate cancer. Although long-term study is necessary to validate oncologic and functional outcomes, our data suggest that the presence of high-risk disease is not a contraindication to a minimally invasive approach for radical prostatectomy at experienced centers.

Relevance of prostate cancer in patients with synchronous invasive bladder urothelial carcinoma: a monocentric retrospective analysis.

PubMed

Dell'Atti, Lucio

2015-03-31

We retrospectively reviewed data of patients with incidental prostate cancer (PCa) who underwent radical cystoprostatectomy (RCP) for invasive bladder cancer and we analyzed their features with regard to incidence, pathologic characteristics, clinical significance, and implications for management. Clinical data and pathological features of 64 patients who underwent standard RCP for bladder cancer were included in this study. Besides the urothelial carcinoma of the urinary bladder, the location and tumor volume of the PCa, prostate apex involvement, Gleason score, pathological staging and surgical margins were evaluated. Clinically significant PCa was defined as a tumor with a Gleason 4 or 5 pattern, stage ≥ pT3, lymph node involvement, positive surgical margin or multifocality of three or more lesions. Postoperative follow-up was scheduled every 3 months in the first year, every 6 months in the second and third year, annually thereafter. 11 out of 64 patients (17.2%) who underwent RCP had incidentally diagnosed PCa. 3 cases (27.3%) were diagnosed as significant PCa, while 8 cases (72.7%) were clinically insignificant. The positive surgical margin of PCa was detected in 1 patient with significant disease. The prostate apex involvement was present in 1 patient of the significant PCa group. Median follow-up period was 47.8 ± 29.2 (range 4-79). During the follow-up, biochemical recurrence occurred in 1 patient (9%). Concerning the cancer specific survival there was no statistical significance (P = 0.326) between the clinically significant and clinical insignificant cancer group. In line with published studies, incidental PCa does not impact on the prognosis of bladder cancer of patients undergoing RCP.

Does Specialty Bias Trump Evidence in the Management of High-risk Prostate Cancer?

PubMed

Kishan, Amar U; Duchesne, Gillian; Wang, Pin-Chieh; Rwigema, Jean-Claude M; Saigal, Christopher; Rettig, Matthew; Steinberg, Michael L; King, Christopher R

2018-06-01

The objective was to query how specialty influences treatment recommendations for high-risk prostate cancer in 3 clinical settings: upfront management, postoperative management, and management of biochemical recurrences (BCRs) after radiotherapy (RT). We hypothesized that specialty bias would manifest in all settings, trumping available evidence. A survey of practicing urologists and radiation oncologists was distributed through electronic mail. Questions pertained to upfront management, postoperative treatment, and local salvage for postradiation BCRs. The associations between 26 selected categorical responses and specialty were assessed using multivariate logistic regression. Training level/expertise, practice setting, percentage of consultation caseload consisting of prostate cancer, and nationality were set as effect modifiers. One thousand two hundred fifty-three physicians (846 radiation oncologists and 407 urologists) completed the survey. Radiation oncologists were more likely to recommend adjuvant RT and consider it to be underutilized, and more likely to recommend salvage RT at lower prostate-specific antigen thresholds (P<0.0001). Urologists were more likely to recommend salvage radical prostatectomy or cryoablation for local salvage after RT, whereas radiation oncologists were more likely to recommend RT-based modalities and more likely to report that local salvage was underutilized after RT (P<0.0001). Urologists were more likely to report that upfront radical prostatectomy was a better definitive treatment (P<0.0001), whereas radiation oncologists were more likely to report the opposite (P=0.005). Specialty biases permeate recommendations for upfront management and management in the postoperative and post-RT BCR setting, irrespective of available evidence. These data reveal the critical need for multidisciplinary clinics and cross-specialty training as potential solutions for overcoming specialty bias.

Chemokine Ligand 5 (CCL5) and chemokine receptor (CCR5) genetic variants and prostate cancer risk among men of African Descent: a case-control study

PubMed Central

2012-01-01

Background Chemokine and chemokine receptors play an essential role in tumorigenesis. Although chemokine-associated single nucleotide polymorphisms (SNPs) are associated with various cancers, their impact on prostate cancer (PCA) among men of African descent is unknown. Consequently, this study evaluated 43 chemokine-associated SNPs in relation to PCA risk. We hypothesized inheritance of variant chemokine-associated alleles may lead to alterations in PCA susceptibility, presumably due to variations in antitumor immune responses. Methods Sequence variants were evaluated in germ-line DNA samples from 814 African-American and Jamaican men (279 PCA cases and 535 controls) using Illumina’s Goldengate genotyping system. Results Inheritance of CCL5 rs2107538 (AA, GA+AA) and rs3817655 (AA, AG, AG+AA) genotypes were linked with a 34-48% reduction in PCA risk. Additionally, the recessive and dominant models for CCR5 rs1799988 and CCR7 rs3136685 were associated with a 1.52-1.73 fold increase in PCA risk. Upon stratification, only CCL5 rs3817655 and CCR7 rs3136685 remained significant for the Jamaican and U.S. subgroups, respectively. Conclusions In summary, CCL5 (rs2107538, rs3817655) and CCR5 (rs1799988) sequence variants significantly modified PCA susceptibility among men of African descent, even after adjusting for age and multiple comparisons. Our findings are only suggestive and require further evaluation and validation in relation to prostate cancer risk and ultimately disease progression, biochemical/disease recurrence and mortality in larger high-risk subgroups. Such efforts will help to identify genetic markers capable of explaining disproportionately high prostate cancer incidence, mortality, and morbidity rates among men of African descent. PMID:23168091

Decision-making tools in prostate cancer: from risk grouping to nomograms.

PubMed

Fontanella, Paolo; Benecchi, Luigi; Grasso, Angelica; Patel, Vipul; Albala, David; Abbou, Claude; Porpiglia, Francesco; Sandri, Marco; Rocco, Bernardo; Bianchi, Giampaolo

2017-12-01

Prostate cancer (PCa) is the most common solid neoplasm and the second leading cause of cancer death in men. After the Partin tables were developed, a number of predictive and prognostic tools became available for risk stratification. These tools have allowed the urologist to better characterize this disease and lead to more confident treatment decisions for patients. The purpose of this study is to critically review the decision-making tools currently available to the urologist, from the moment when PCa is first diagnosed until patients experience metastatic progression and death. A systematic and critical analysis through Medline, EMBASE, Scopus and Web of Science databases was carried out in February 2016 as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search was conducted using the following key words: "prostate cancer," "prediction tools," "nomograms." Seventy-two studies were identified in the literature search. We summarized the results into six sections: Tools for prediction of life expectancy (before treatment), Tools for prediction of pathological stage (before treatment), Tools for prediction of survival and cancer-specific mortality (before/after treatment), Tools for prediction of biochemical recurrence (before/after treatment), Tools for prediction of metastatic progression (after treatment) and in the last section biomarkers and genomics. The management of PCa patients requires a tailored approach to deliver a truly personalized treatment. The currently available tools are of great help in helping the urologist in the decision-making process. These tests perform very well in high-grade and low-grade disease, while for intermediate-grade disease further research is needed. Newly discovered markers, genomic tests, and advances in imaging acquisition through mpMRI will help in instilling confidence that the appropriate treatments are being offered to patients with prostate cancer.

A randomized, phase II study of pazopanib in castrate-sensitive prostate cancer: a University of Chicago Phase II Consortium/Department of Defense Prostate Cancer Clinical Trials Consortium study.

PubMed

Ward, J E; Karrison, T; Chatta, G; Hussain, M; Shevrin, D; Szmulewitz, R Z; O'Donnell, P H; Stadler, W M; Posadas, E M

2012-03-01

Intermittent androgen suppression (IAS) is an increasingly popular treatment option for castrate-sensitive prostate cancer. On the basis of previous data with anti-angiogenic strategies, we hypothesized that pan-inhibition of the vascular endothelial growth factor receptor using pazopanib during the IAS off period would result in prolonged time to PSA failure. Men with biochemically recurrent prostate cancer, whose PSA was <0.5 ng ml(-1) after 6 months of androgen deprivation therapy were randomized to pazopanib 800 mg daily or observation. The planned primary outcome was time to PSA progression >4.0 ng ml(-1). Thirty-seven patients were randomized. Of 18 patients randomized to pazopanib, at the time of study closure, 4 had progressive disease, 1 remained on treatment and 13 (72%) electively disenrolled, the most common reason being patient request due to grade 1/2 toxicity (8 patients). Two additional patients were removed from treatment due to adverse events. Of 19 patients randomized to observation, at the time of study closure, 4 had progressive disease, 7 remained under protocol-defined observation and 8 (42%) had disenrolled, most commonly due to non-compliance with protocol visits (3 patients). Because of high dropout rates in both arms, the study was halted. IAS is a treatment approach that may facilitate investigation of novel agents in the hormone-sensitive state. This trial attempted to investigate the role of antiangiogenic therapy in this setting, but encountered several barriers, including toxicities and patient non-compliance, which can make implementation of such a study difficult. Future investigative efforts in this arena should carefully consider drug toxicity and employ a design that maximizes patient convenience to reduce the dropout rate.

Irreversible Electroporation for Prostate Cancer as Salvage Treatment Following Prior Radiation and Cryotherapy.

PubMed

Murray, Katie S; Akin, Oguz; Coleman, Jonathan A

2017-01-01

Salvage treatment options after localized primary treatment failure of prostate cancer are limited and associated with risk for serious complications. We report on the management details of a 57-year-old African American man treated with partial-gland ablation using irreversible electroporation following local recurrence after brachytherapy and prior salvage cryoablation. Therapeutic and functional outcomes were assessed by conventional means, including serum prostate-specific antigen values and prostate biopsy results.

Integrative analysis identifies targetable CREB1/FoxA1 transcriptional co-regulation as a predictor of prostate cancer recurrence.

PubMed

Sunkel, Benjamin; Wu, Dayong; Chen, Zhong; Wang, Chiou-Miin; Liu, Xiangtao; Ye, Zhenqing; Horning, Aaron M; Liu, Joseph; Mahalingam, Devalingam; Lopez-Nicora, Horacio; Lin, Chun-Lin; Goodfellow, Paul J; Clinton, Steven K; Jin, Victor X; Chen, Chun-Liang; Huang, Tim H-M; Wang, Qianben

2016-05-19

Identifying prostate cancer-driving transcription factors (TFs) in addition to the androgen receptor promises to improve our ability to effectively diagnose and treat this disease. We employed an integrative genomics analysis of master TFs CREB1 and FoxA1 in androgen-dependent prostate cancer (ADPC) and castration-resistant prostate cancer (CRPC) cell lines, primary prostate cancer tissues and circulating tumor cells (CTCs) to investigate their role in defining prostate cancer gene expression profiles. Combining genome-wide binding site and gene expression profiles we define CREB1 as a critical driver of pro-survival, cell cycle and metabolic transcription programs. We show that CREB1 and FoxA1 co-localize and mutually influence each other's binding to define disease-driving transcription profiles associated with advanced prostate cancer. Gene expression analysis in human prostate cancer samples found that CREB1/FoxA1 target gene panels predict prostate cancer recurrence. Finally, we showed that this signaling pathway is sensitive to compounds that inhibit the transcription co-regulatory factor MED1. These findings not only reveal a novel, global transcriptional co-regulatory function of CREB1 and FoxA1, but also suggest CREB1/FoxA1 signaling is a targetable driver of prostate cancer progression and serves as a biomarker of poor clinical outcomes. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

[Gap between postulated and real outcome quality of radical prostatectomy].

PubMed

Hampel, C; Roos, F; Thüroff, J W; Neisius, A

2015-11-01

Certified Prostate Centers proclaim congruent process and outcome quality results for treatment of prostate carcinoma. Therapy in accordance with the guidelines after presentation of the patient in an interdisciplinary conference and regular documented follow up are not in themselves a guarantee for good quality results (complication free, continence, erectile function, negative surgical margins, biochemical recurrence free), and are significantly influenced by factors not contained within the certification framework. An association between exceeding the minimum number of operations and quality assurance exists, if at all, only vaguely and on no account justifies the absolute numbers necessary for certification. Although good measuring instruments for a Pentafecta analysis are available, the gathering of quality results for a center are limited to questionnaires for functional quality results and in the non-differentiated request for a pT2R1 rate of under 10 % for oncological quality results. The reasons for this systematic ignoring of the for the patient so important quality results with a simultaneous excessive regard for standardizing organizational procedure processes are manifold. They comprise valid verifiability of process quality, the unclear effects of standardized treatment pathways on actual operation quality and the capitulation to statistical and patient determined problems with sufficient acquisition of comparable functional OP results. Whereas the outcome quality is more important than the process quality for patients with prostate carcinoma, the certified centers conduct themselves in exactly the opposite manner, thus creating a virtually insoluble dilemma.

68Ga-PSMA PET/CT in Patients with Rising Prostatic-Specific Antigen After Definitive Treatment of Prostate Cancer: Detection Efficacy and Diagnostic accuracy.

PubMed

Hamed, Maged Abdel Galil; Basha, Mohammad Abd Alkhalik; Ahmed, Hussien; Obaya, Ahmed Ali; Afifi, Amira Hamed Mohamed; Abdelbary, Eman H

2018-06-20

68 Ga-prostate-specific membrane antigen-11 ( 68 Ga-PSMA-11) is a recently developed positron emission tomography (PET) tracer that can detect prostate cancer (PC) relapses and metastases with high contrast resolution. The aim of this study was to assess the detection efficacy and diagnostic accuracy of 68 Ga-PSMA PET/CT image in patients with rising prostatic-specific antigen (PSA) after treatment of PC. The present prospective study included 188 patients who exhibited rising of PSA level on a routine follow-up examination after definitive treatment of PC. All patients underwent a 68 Ga-PSMA PET/CT examination. For each patient, we determined the disease stage, the Gleason score, and the maximum standardized uptake value of the local recurrence and extraprostatic metastases. The detection efficacy and diagnostic accuracy of 68 Ga-PSMA PET/CT were established by histopathology and clinical and imaging follow-up as the reference standards. 68 Ga-PSMA PET/CT detected tumour relapse in 165 patients (35 patients had local recurrence, 106 patients had extraprostatic metastases, and 24 patients had combined lesions). The sensitivity, specificity, and accuracy values of 68 Ga-PSMA PET/CT examination in the detection of PC recurrence were 98.8%, 100%, and 98.8%, respectively. 68 Ga-PSMA PET/CT revealed an overall detection rate of 87.8% (165/188) in patients with rising PSA (median of 2.2 ng/mL, and range of 0.01-70 ng/mL). 68 Ga-PSMA PET/CT is a valuable tool for the detection of PC local recurrence or extraprostatic metastases following rising PSA levels after primary definitive therapy and should be incorporated during routine work-up. Copyright © 2018. Published by Elsevier Inc.

Aspirin and Statin Nonuse Associated With Early Biochemical Failure After Prostate Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zaorsky, Nicholas G.; Buyyounouski, Mark K., E-mail: mark.buyyounouski@fccc.edu; Li, Tianyu

Purpose: To present the largest retrospective series investigating the effect of aspirin and statins, which are hypothesized to have antineoplastic properties, on biochemical failure (nadir plus 2 ng/mL) after prostate radiation therapy (RT). Methods and Materials: Between 1989 and 2006, 2051 men with clinically localized prostate cancer received definitive RT alone (median dose, 76 Gy). The rates of aspirin use and statin use (defined as any use at the time of RT or during follow-up) were 36% and 34%, respectively. The primary endpoint of the study was an interval to biochemical failure (IBF) of less than 18 months, which hasmore » been shown to be the single strongest predictor of distant metastasis, prostate cancer survival, and overall survival after RT. Patient demographic characteristics and tumor staging factors were assessed with regard to associations with the endpoint. Univariate analysis was performed with the {chi}{sup 2} test for categorical variables and the Wilcoxon test for continuous variables. Multivariable analysis was performed with a multiple logistic regression. Results: The median follow-up was 75 months. Univariate analysis showed that an IBF of less than 18 months was associated with aspirin nonuse (P<.0001), statin nonuse (P<.0001), anticoagulant nonuse (P=.0006), cardiovascular disease (P=.0008), and prostate-specific antigen (continuous) (P=.008) but not with Gleason score, age, RT dose, or T stage. On multivariate analysis, only aspirin nonuse (P=.0012; odds ratio, 2.052 [95% confidence interval, 1.328-3.172]) and statin nonuse (P=.0002; odds ratio, 2.465 [95% confidence interval, 1.529-3.974]) were associated with an IBF of less than 18 months. Conclusions: In patients who received RT for prostate cancer, aspirin or statin nonuse was associated with early biochemical failure, a harbinger of distant metastasis and death. Further study is needed to confirm these findings and to determine the optimal dosing and schedule, as well as the relative benefits and risks, of both therapies in combination with RT.« less

DNA Ploidy Measured on Archived Pretreatment Biopsy Material May Correlate With Prostate-Specific Antigen Recurrence After Prostate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keyes, Mira, E-mail: mkeyes@bccancer.bc.ca; MacAulay, Calum; Hayes, Malcolm

Purpose: To explore whether DNA ploidy of prostate cancer cells determined from archived transrectal ultrasound-guided biopsy specimens correlates with disease-free survival. Methods and Materials: Forty-seven failures and 47 controls were selected from 1006 consecutive low- and intermediate-risk patients treated with prostate {sup 125}I brachytherapy (July 1998-October 2003). Median follow-up was 7.5 years. Ten-year actuarial disease-free survival was 94.1%. Controls were matched using age, initial prostate-specific antigen level, clinical stage, Gleason score, use of hormone therapy, and follow-up (all P nonsignificant). Seventy-eight specimens were successfully processed; 27 control and 20 failure specimens contained more than 100 tumor cells were used formore » the final analysis. The Feulgen-Thionin stained cytology samples from archived paraffin blocks were used to determine the DNA ploidy of each tumor by measuring integrated optical densities. Results: The samples were divided into diploid and aneuploid tumors. Aneuploid tumors were found in 16 of 20 of the failures (80%) and 8 of 27 controls (30%). Diploid DNA patients had a significantly lower rate of disease recurrence (P=.0086) (hazard ratio [HR] 0.256). On multivariable analysis, patients with aneuploid tumors had a higher prostate-specific antigen failure rate (HR 5.13). Additionally, those with “excellent” dosimetry (V100 >90%; D90 >144 Gy) had a significantly lower recurrence rate (HR 0.25). All patients with aneuploid tumors and dosimetry classified as “nonexcellent” (V100 <90%; D90 <144 Gy) (5 of 5) had disease recurrence, compared with 40% of patients with aneuploid tumors and “excellent” dosimetry (8 of 15). In contrast, dosimetry did not affect the outcome for diploid patients. Conclusions: Using core biopsy material from archived paraffin blocks, DNA ploidy correctly classified the majority of failures and nonfailures in this study. The results suggest that DNA ploidy can be used as a useful marker for aggressiveness of localized prostate cancer. A larger study will be necessary to further confirm our hypothesis.« less

Dystrophic calcification of the prostate after cryotherapy.

PubMed

Dru, Christopher; Bender, Leon

2014-01-01

We present a previously undocumented complication of dystrophic calcification of the prostate after cryotherapy. An 87-year-old male presented with recurrent lower urinary tract infections and was found to have an obstructing large calcified mass in the right lobe of the prostate. Subsequently, he underwent transurethral resection of the prostate (TURP) and bladder neck with laser lithotripsy to remove the calculus. We propose that chronic inflammation and necrosis of the prostate from cryotherapy resulted in dystrophic calcification of the prostate. As the use of cryotherapy for the treatment of localized prostate cancer continues to increase, it is important that clinicians be aware of this scenario and the technical challenges it poses.

Incidental Detection of Type B2 Thymoma on 68Ga-Labeled Prostate-Specific Membrane Antigen PET/CT Imaging.

PubMed

Krishnaraju, Venkata Subramanian; Basher, Rajender Kumar; Singh, Harmandeep; Singh, Shrawan Kumar; Bal, Amanjit; Mittal, Bhagwant Rai

2018-05-01

Ga-labeled prostate-specific membrane antigen is a novel radiotracer for imaging of prostate cancer. We report a hormonally treated patient with prostate carcinoma, presenting with lower urinary tract symptoms and rising prostate-specific antigen levels, who underwent Ga-labeled prostate-specific membrane antigen PET/CT for suspected recurrence. No tracer avid lesion was noted in the prostate gland and locoregional area. However, intense tracer avid heterogeneously enhancing soft tissue lesion with cystic areas and coarse calcifications was seen in the anterior mediastinum. PET/CT-guided biopsy from the mediastenal lesion revealed type B2 thymoma.

Is the apical soft tissue margin a better predictor of biochemical recurrence than the surgical specimen?

PubMed

Godoy, Guilherme; Tareen, Basir U; Lepor, Herbert

2011-01-01

To identify predictors of apical surgical margin (ASM) and apical soft tissue margin (ASTM), determine if the ASTM is a better predictor of biochemical recurrence (BR) than the ASM, and ascertain the impact of apical biopsies on BR rates. One thousand three hundred eight consecutive men underwent open radical retropubic prostatectomy (RP) between October 2000 and December 2006. Circumferential biopsies of the ASTM were obtained intraoperatively and submitted for frozen section analysis. Logistic regression models were utilized to identify the factors associated with the presence of positive ASMs and ASTMs. The estimated 5-year risk of BR was calculated by the Kaplan-Meier method. Overall, 43 (3.3%) and 86 (6.6%) of cases exhibited positive ASM and ASTM, respectively. ASM was significantly associated with higher mean serum prostate-specific antigen levels, presence of perineural invasion, and greater volume of tumor in the biopsy specimen. None of these factors were observed to be associated with the presence of cancer in the ASTMs. In the multivariate analysis, only the presence of perineural invasion was a significant independent predictor of ASMs. The estimated 5-year BR rates in the positive ASMs only, ASTMs only, and both positive ASMs and ASTMs groups were 48.6%, 4.7%, and 38.8%, respectively. A positive ASM was associated with a significantly greater risk of BR compared with a positive ASTM. The very low estimated risk of BR at 5 years in cases with ASTM suggests that performing the ASTM biopsies may increase the cure rates achieved with RP. Copyright © 2011 Elsevier Inc. All rights reserved.

Comparison of 68Ga-PSMA-11 and 18F-Fluciclovine PET/CT in a Case Series of 10 Patients with Prostate Cancer Recurrence.

PubMed

Calais, Jeremie; Fendler, Wolfgang P; Herrmann, Ken; Eiber, Matthias; Ceci, Francesco

2018-05-01

This was a head-to-head comparison between 68 Ga-labeled prostate-specific membrane antigen (PSMA)-11 and 18 F-fluciclovine PET/CT in a series of 10 patients with prostate cancer (PCa) recurrence. Methods: In total, 288 patients with PCa recurrence were enrolled in a prospective study of 68 Ga-PSMA-11 PET/CT imaging for recurrent disease localization (ClinicalTrials.gov identifier NCT02940262). We retrospectively identified 10 patients who underwent clinically indicated 18 F-fluciclovine PET/CT prior to enrollment. Results: The median time between the 2 scans was 2.2 mo (range, 0.2-4.2 mo). The median prostate-specific antigen (PSA) value was 1.0 ng/mL (mean, 4.7 ng/mL; range, 0.13-18.1 ng/mL) and 1.1 ng/mL (mean, 6.2 ng/mL; range, 0.24-31.3 ng/mL) at the time of 18 F-fluciclovine and 68 Ga-PSMA-11 PET/CT, respectively. Five of 10 patients (50%) were negative with 18 F-fluciclovine but positive with 68 Ga-PSMA-11 PET/CT. Two of 10 patients (20%) were positive with both 18 F-fluciclovine and 68 Ga-PSMA-11 PET/CT, but 68 Ga-PSMA-11 PET/CT showed additional lymph nodes metastasis. Three of 10 patients (30%) were negative with both 18 F-fluciclovine and 68 Ga-PSMA-11 PET/CT. Conclusion: This case series suggests improved detection rates for 68 Ga-PSMA-11 PET/CT when compared with 18 F-fluciclovine PET/CT in patients with recurrent PCa. Prospective trials designed to directly compare the two should be initiated. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Clinically Significant Prostate Cancer Local Recurrence After Radiation Therapy Occurs at the Site of Primary Tumor: Magnetic Resonance Imaging and Step-Section Pathology Evidence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pucar, Darko; Hricak, Hedvig; Shukla-Dave, Amita

2007-09-01

Purpose: To determine whether prostate cancer local recurrence after radiation therapy (RT) occurs at the site of primary tumor by retrospectively comparing the tumor location on pre-RT and post-RT magnetic resonance imaging (MRI) and using step-section pathology after salvage radical prostatectomy (SRP) as the reference standard. Methods and Materials: Nine patients with localized prostate cancer were treated with intensity modulated RT (69-86.4 Gy), and had pre-RT and post-RT prostate MRI, biopsy-proven local recurrence, and SRP. The location and volume of lesions on pre-RT and post-RT MRI were correlated with step-section pathology findings. Tumor foci >0.2 cm{sup 3} and/or resulting inmore » extraprostatic disease on pathology were considered clinically significant. Results: All nine significant tumor foci (one in each patient; volume range, 0.22-8.63 cm{sup 3}) were detected both on pre-RT and post-RT MRI and displayed strikingly similar appearances on pre-RT and post-RT MRI and step-section pathology. Two clinically insignificant tumor foci ({<=}0.06 cm{sup 3}) were not detected on imaging. The ratios between tumor volumes on pathology and on post-RT MRI ranged from 0.52 to 2.80. Conclusions: Our study provides a direct visual confirmation that clinically significant post-RT local recurrence occurs at the site of primary tumor. Our results are in agreement with reported clinical and pathologic results and support the current practice of boosting the radiation dose within the primary tumor using imaging guidance. They also suggest that monitoring of primary tumor with pre-RT and post-RT MRI could lead to early detection of local recurrence amenable to salvage treatment.« less

Toxicity and efficacy of salvage carbon 11-choline positron emission tomography/computed tomography-guided radiation therapy in patients with lymph node recurrence of prostate cancer.

PubMed

Fodor, Andrei; Berardi, Genoveffa; Fiorino, Claudio; Picchio, Maria; Busnardo, Elena; Kirienko, Margarita; Incerti, Elena; Dell'Oca, Italo; Cozzarini, Cesare; Mangili, Paola; Pasetti, Marcella; Calandrino, Riccardo; Gianolli, Luigi; Di Muzio, Nadia G

2017-03-01

To report the 3-year toxicity and outcomes of carbon 11 (11C)-choline-positron emission tomography (PET)/computed tomography (CT)-guided radiotherapy (RT), delivered via helical tomotherapy (HTT; Tomotherapy ® Hi-Art II ® Treatment System, Accuray Inc., Sunnyvale, CA, USA) after lymph node (LN) relapses in patients with prostate cancer. From January 2005 to March 2013, 81 patients with biochemical recurrence after surgery, with or without adjuvant/salvage RT or radical RT, and with evidence of LN 11C-choline-PET/CT pathological uptake, underwent HTT (median [range] prostate-specific antigen level 2.59 [0.61-187] ng/mL). Of the 81 patients, 72 were treated at the pelvic and/or lumbar-aortic LN chain with HTT at 51.8 Gy/28 fr and with simultaneous integrated boost to a median dose of 65.5 Gy on the pathological uptake sites detected by 11C-choline-PET/CT. Nine patients were treated without simultaneous integrated boost (50-65.5 Gy, 25-30 fr). With a median (range) follow-up of 36 (9-116) months, 91.4% of the patients had a PSA reduction 3 months after HTT. The 3-year overall, local relapse-free and clinical relapse-free survival rates were 80.0, 89.8 and 61.8%, respectively. The 3-year actuarial incidences of ≥grade 2 rectal and ≥grade 2 genitourinary toxicity were 6.6% (±2.9%) and 26.3% (±5.5%), respectively. A PSA nadir of ≥0.26 ng/mL (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.7-7.7; P = 0.001), extrapelvic 11C-choline-PET/CT-positive LN location (HR 2.4, 95% CI 0.9-6.4; P = 0.07), RT previous to HTT (HR 2.7; 95% CI 1.07-6.9, P = 0.04) and number of positive LNs (HR 1.13, 95% CI 1.04-1.22; P = 0.003) were the main predictors of clinical relapse after HTT. 11C-choline-PET/CT-guided HTT is safe and effective in the treatment of LN relapses of prostate cancer in previously treated patients. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

High Intensity Focused Ultrasound (HIFU) as a Salvage Treatment for Recurrent Prostate Cancer after Brachytherapy — a Feasibility Study

NASA Astrophysics Data System (ADS)

Chapman, Alexander T.; Rivens, Ian H.; Thompson, Alan C.; ter Haar, Gail R.

2007-05-01

HIFU may be an effective salvage treatment for patients who develop local recurrence after permanent low-dose brachytherapy. It has been suggested that the presence of seeds in the prostate may obstruct the HIFU beam or alter the heating characteristics of the prostate tissue. Acoustic field measurements were made using a membrane hydrophone and lesioning experiments were carried out in ex vivo bovine liver. These revealed a significant effect of the seeds on the HIFU focal region as well as a reduction in lesion length when seeds were placed in a pre-focal position. Further work is needed to evaluate the full effects of implanted brachytherapy seeds on the clinical delivery of HIFU.

Are 10-, 10-12-, or > 12-mm prostate biopsy core quality control cutoffs reasonable?

PubMed

Sanches, Brunno C F; Lalli, Ana Luiza; Azal Neto, Wilmar; Billis, Athanase; Reis, Leonardo Oliveira

2018-07-01

To explore the role of prostate biopsy core length on prediction of index tumor clinical significance and localization on radical prostatectomy (RP) and time to recurrence, hypothesizing 10-, 10-12-, or > 12-mm minimum core as potential biopsy quality control. Assessed 2424 prostate biopsy cores and corresponding RP of 202 patients submitted to the first set of 12 cores prostate biopsy between 2010 and 2015. Analyzed biopsy core length, age, prostate volume (PV), free and total PSA ratio, PSA density, RP index tumor clinical significance, extension, localization, surgical margins, and cancer control. Prostate biopsy confronted to surgical specimens defined Gleason grade-grouping system (1-5) agreement. Median age was 63.7 years, PSA 10.1 ng/dl, PSA density 28%, and mean follow-up 5 years. Recurrence was identified in 64 (31.7%) patients and predicted by PSA > 10 at time of diagnosis (p = 0.008), seminal vesicle invasion (p = 0.0019), core tumor percentage (p = 0.033), and tumor localization predominantly in the prostate base (p = 0017). The mean core length was longer in index tumor positive cores (p = 0.043) and in tumors classified as clinically insignificant (p = 0.011), without impact on tumor localization (basal vs apical p = 0.592; left vs. right p = 0.320). Biopsy core length categories (≤ 10, 10-12 and > 12 mm) did not significantly impact Gleason grade-grouping agreement or time to recurrence (p > 0.05). Core length was not significantly different in all Gleason grade-groupings 1-5 (p = 0.312). Prostate biopsy core length impacts tumor characterization; however, 10 mm minimum core length and even 10-12- and > 12-mm categories failed as a biopsy quality control in our data.

Herniated Thoracic Spleen Mimicking Lung Metastasis on 68Ga-Labeled Prostate-Specific Membrane Antigen PET/CT in a Patient With Prostate Cancer.

PubMed

Malik, Dharmender; Basher, Rajender K; Sood, Apurva; Devana, Sudheer Kumar; Bhattacharya, Anish; Mittal, Bhagwant Rai

2017-06-01

We report a case of clinically asymptomatic patient of prostate cancer who was previously subjected to radical prostatectomy presenting with a rising serum prostate-specific antigen level of 6.6 ng/mL. Whole-body PET/CT with Ga-labeled prostate-specific membrane antigen ligand was performed to assess for disease recurrence, which revealed an intense tracer uptake in a soft tissue mass in left hemithorax mimicking lung metastasis; which later turned out to be splenic tissue.

Gleason pattern 5 is the strongest pathologic predictor of recurrence, metastasis, and prostate cancer-specific death in patients receiving salvage radiation therapy following radical prostatectomy.

PubMed

Jackson, William; Hamstra, Daniel A; Johnson, Skyler; Zhou, Jessica; Foster, Benjamin; Foster, Corey; Li, Darren; Song, Yeohan; Palapattu, Ganesh S; Kunju, Lakshmi P; Mehra, Rohit; Feng, Felix Y

2013-09-15

The presence of Gleason pattern 5 (GP5) at radical prostatectomy (RP) has been associated with worse clinical outcome; however, this pathologic variable has not been assessed in patients receiving salvage radiation therapy (SRT) after a rising prostate-specific antigen level. A total of 575 patients who underwent primary RP for localized prostate cancer and subsequently received SRT at a tertiary medical institution were reviewed retrospectively. Primary outcomes of interest were biochemical failure (BF), distant metastasis (DM), and prostate cancer-specific mortality (PCSM), which were assessed via univariate analysis and Fine and Grays competing risks multivariate models. On pathologic evaluation, 563 (98%) patients had a documented Gleason score (GS). The median follow-up post-SRT was 56.7 months. A total of 60 (10.7%) patients had primary, secondary, or tertiary GP5. On univariate analysis, the presence of GP5 was prognostic for BF (hazard ratio [HR] 3.3; P < .0001), DM (HR:11.1, P < .0001), and PCSM (HR:8.8, P < .0001). Restratification of the Gleason score to include GP5 as a distinct entity resulted in improved prognostic capability. Patients with GP5 had clinically worse outcomes than patients with GS8(4+4). On multivariate analysis, the presence of GP5 was the most adverse pathologic predictor of BF (HR 2.9; P < .0001), DM (HR 14.8; P < .0001), and PCSM (HR 5.7; P < .0001). In the setting of SRT for prostate cancer, the presence of GP5 is a critical pathologic predictor of BF, DM, and PCSM. Traditional GS risk stratification fails to fully utilize the prognostic capabilities of individual Gleason patterns among men receiving SRT post-RP. © 2013 American Cancer Society.

Technical Note: Method to correlate whole-specimen histopathology of radical prostatectomy with diagnostic MR imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGrath, Deirdre M., E-mail: d.mcgrath@sheffield.ac.uk; Lee, Jenny; Foltz, Warren D.

Purpose: Validation of MRI-guided tumor boundary delineation for targeted prostate cancer therapy is achieved via correlation with gold-standard histopathology of radical prostatectomy specimens. Challenges to accurate correlation include matching the pathology sectioning plane with the in vivo imaging slice plane and correction for the deformation that occurs between in vivo imaging and histology. A methodology is presented for matching of the histological sectioning angle and position to the in vivo imaging slices. Methods: Patients (n = 4) with biochemical failure following external beam radiotherapy underwent diagnostic MRI to confirm localized recurrence of prostate cancer, followed by salvage radical prostatectomy. High-resolutionmore » 3-D MRI of the ex vivo specimens was acquired to determine the pathology sectioning angle that best matched the in vivo imaging slice plane, using matching anatomical features and implanted fiducials. A novel sectioning device was developed to guide sectioning at the correct angle, and to assist the insertion of reference dye marks to aid in histopathology reconstruction. Results: The percentage difference in the positioning of the urethra in the ex vivo pathology sections compared to the positioning in in vivo images was reduced from 34% to 7% through slicing at the best match angle. Reference dye marks were generated, which were visible in ex vivo imaging, in the tissue sections before and after processing, and in histology sections. Conclusions: The method achieved an almost fivefold reduction in the slice-matching error and is readily implementable in combination with standard MRI technology. The technique will be employed to generate datasets for correlation of whole-specimen prostate histopathology with in vivo diagnostic MRI using 3-D deformable registration, allowing assessment of the sensitivity and specificity of MRI parameters for prostate cancer. Although developed specifically for prostate, the method is readily adaptable to other types of whole tissue specimen, such as mastectomy or liver resection.« less

Hypofractionated radiation therapy for prostate cancer: The McGill University Health Center experience.

PubMed

Barbosa Neto, O; Souhami, L; Faria, S

2015-10-01

In 2002, at the McGill University Health Centre, we began a program of hypofractionated radiotherapy for patients with low risk prostate cancer as an alternative to conventionally fractionated radiotherapy. Our initial hypofractionation regimen was 66 Gy given in 22 fractions, prescribed to the isocenter, delivered with 3D-conformal radiotherapy plan. The clinical target volume was the prostate gland and the planning target volume consisted of the clinical target volume plus a 7-mm margin in all directions. Hormonal therapy was not given to any patient. The long-term results for this group of patients confirmed the feasibility, good tolerance and excellent disease control of the regimen with the extra-benefit of being convenient to both patients and the health system by shortening treatment duration. The outcomes of this approach stimulated us to use hypofractionation in patients with intermediate-risk. Analysis of 100 intermediate-risk patients receiving our hypofractionated radiotherapy regimen (no hormones) shows, at median follow-up of 75 months, 8-year biochemical recurrence free and cancer specific survival rates of 90% and 95%, respectively, with acceptable toxicity. Our technique changed from 3D to intensity modulated radiotherapy with the dose adjusted to 60 Gy in 20 fractions. Lastly, we have expanded the program to high-risk patients where IMRT treatments are given to the pelvic nodes (44 Gy in 20 fractions) with a simultaneous integrated boost delivery to the prostate (60 Gy in the same 20 fractions). Our long-term results have shown that moderate hypofractionated radiotherapy for prostate cancer is safe and provides good tumor control comparable to high-dose conventionally fractionated radiotherapy. This hypofractionated regimen has been routinely used in our institution. Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Prognostic Utility of Cell Cycle Progression Score in Men With Prostate Cancer After Primary External Beam Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Freedland, Stephen J., E-mail: steve.freedland@duke.edu; Department of Surgery; Department of Pathology, Duke University School of Medicine, Durham, North Carolina

Purpose: To evaluate the prognostic utility of the cell cycle progression (CCP) score, a RNA signature based on the average expression level of 31 CCP genes, for predicting biochemical recurrence (BCR) in men with prostate cancer treated with external beam radiation therapy (EBRT) as their primary curative therapy. Methods and Materials: The CCP score was derived retrospectively from diagnostic biopsy specimens of men diagnosed with prostate cancer from 1991 to 2006 (n=141). All patients were treated with definitive EBRT; approximately half of the cohort was African American. Outcome was time from EBRT to BCR using the Phoenix definition. Median follow-upmore » for patients without BCR was 4.8 years. Association with outcome was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. Results: Of 141 patients, 19 (13%) had BCR. The median CCP score for patient samples was 0.12. In univariable analysis, CCP score significantly predicted BCR (P=.0017). The hazard ratio for BCR was 2.55 for 1-unit increase in CCP score (equivalent to a doubling of gene expression). In a multivariable analysis that included Gleason score, prostate-specific antigen, percent positive cores, and androgen deprivation therapy, the hazard ratio for CCP changed only marginally and remained significant (P=.034), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. With 10-year censoring, the CCP score was associated with prostate cancer-specific mortality (P=.013). There was no evidence for interaction between CCP and any clinical variable, including ethnicity. Conclusions: Among men treated with EBRT, the CCP score significantly predicted outcome and provided greater prognostic information than was available with clinical parameters. If validated in a larger cohort, CCP score could identify high-risk men undergoing EBRT who may need more aggressive therapy.« less

Five-Year Biochemical Results, Toxicity, and Patient-Reported Quality of Life After Delivery of Dose-Escalated Image Guided Proton Therapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bryant, Curtis, E-mail: cbryant@floridaproton.org; Smith, Tamara L.; Henderson, Randal H.

Purpose: To report clinical outcomes in patients treated with image guided proton therapy (PT) for localized prostate cancer. Methods and Materials: The medical records of 1327 men were reviewed. Each man was enrolled on an outcomes tracking study. Dual enrollment on a prospective clinical trial was allowed. Each patient was treated for localized prostate cancer with PT at our institution between 2006 and 2010. Ninety-eight percent of patients received 78 Gy (radiobiological equivalent [RBE]) or higher; 18% received androgen deprivation therapy (ADT). The 5-year freedom from biochemical progression (FFBP), distant metastasis-free survival, and cause-specific survival rates are reported for each risk group. Datamore » on patient-reported quality of life and high-grade toxicities were prospectively collected and reported. A multivariate analysis was performed to identify clinical predictors of biochemical failure and urologic toxicity. Results: The median follow-up time was 5.5 years. The 5-year FFBP rates were 99%, 94%, and 74% in low-risk, intermediate-risk, and high-risk patients, respectively. The actuarial 5-year rates of late grade 3+ Common Terminology Criteria for Adverse Events, version 4.0, gastrointestinal (GI) and genitourinary (GU) toxicity were 0.6% and 2.9%, respectively. Multivariate analysis showed a significant correlation between grade 3+ GU toxicity and pretreatment prostate reductive procedures (P<.0001), prostate volume (P=.0085), pretreatment α-blockers (P=.0067), diabetes (P=.0195), and dose–volume histogram parameters (P=.0208). The median International Prostate Symptom Scores pretreatment scores and scores at 5 years after treatment were 7 and 7, respectively. The mean Expanded Prostate Cancer Index Composite (EPIC) scores significantly declined for sexual summary for patients not receiving ADT (from 67 to 53) between baseline and 5 years. Conclusions: Image guided PT provided excellent biochemical control rates for patients with localized prostate cancer. The actuarial rates of high-grade toxicity were low after PT. From pretreatment to 5 years of follow-up, a significant decline was found only in mean EPIC sexual summary scores. Prospective clinical studies are needed to determine the comparative effectiveness of PT and other radiation treatment strategies.« less

14-3-3η Amplifies Androgen Receptor Actions in Prostate Cancer

PubMed Central

Titus, Mark A.; Tan, Jiann-an; Gregory, Christopher W.; Ford, O. Harris; Subramanian, Romesh R.; Fu, Haian; Wilson, Elizabeth M.; Mohler, James L.; French, Frank S.

2009-01-01

Purpose Androgen receptor (AR) abundance and AR-regulated gene expression in castration-recurrent prostate cancer (CaP) are indicative of AR activation in the absence of testicular androgen. AR transactivation of target genes in castration-recurrent CaP occurs in part through mitogen signaling that amplifies the actions of AR and its coregulators. Herein we report on the role of 14-3-3η in AR action. Experimental Design and Results AR and 14-3-3η co-localized in COS cell nuclei with and without androgen and 14-3-3η promoted AR nuclear localization in the absence of androgen. 14-3-3η interacted with AR in cell-free binding and coimmunoprecipitation assays. In the recurrent human CaP cell line, CWR-R1, native endogenous AR transcriptional activation was stimulated by 14-3-3η at low DHT concentrations and was increased by EGF. Moreover, the DHT and EGF dependent increase in AR transactivation was inhibited by a dominant negative 14-3-3η. In the CWR22 CaP xenograft model, 14-3-3η expression was increased by androgen, suggesting a feed-forward mechanism that potentiates both 14-3-3η and AR actions. 14-3-3η mRNA and protein decreased following castration of tumor bearing mice and increased in tumors of castrate mice after treatment with testosterone. CWR22 tumors that recurred 5 months after castration contained 14-3-3η levels similar to the androgen-stimulated tumors removed before castration. In a human prostate tissue microarray of clinical specimens, 14-3-3η localized with AR in nuclei and the similar amounts expressed in castration-recurrent CaP, androgen-stimulated CaP and benign prostatic hyperplasia were consistent with AR activation in recurrent CaP. Conclusion 14-3-3η enhances androgen and mitogen induced AR transcriptional activity in castration-recurrent CaP. PMID:19996220

Comparative sensitivities of functional MRI sequences in detection of local recurrence of prostate carcinoma after radical prostatectomy or external-beam radiotherapy.

PubMed

Roy, Catherine; Foudi, Fatah; Charton, Jeanne; Jung, Michel; Lang, Hervé; Saussine, Christian; Jacqmin, Didier

2013-04-01

The aim of this retrospective study was to determine the respective accuracies of three types of functional MRI sequences-diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE) MRI, and 3D (1)H-MR spectroscopy (MRS)-in the depiction of local prostate cancer recurrence after two different initial therapy options. From a cohort of 83 patients with suspicion of local recurrence based on prostate-specific antigen (PSA) kinetics who were imaged on a 3-T MRI unit using an identical protocol including the three functional sequences with an endorectal coil, we selected 60 patients (group A, 28 patients who underwent radical prostatectomy; group B, 32 patients who underwent external-beam radiation) who had local recurrence ascertained on the basis of a transrectal ultrasound-guided biopsy results and a reduction in PSA level after salvage therapy. All patients presented with a local relapse. Sensitivity with T2-weighted MRI and 3D (1)H-MRS sequences was 57% and 53%, respectively, for group A and 71% and 78%, respectively, for group B. DCE-MRI alone showed a sensitivity of 100% and 96%, respectively, for groups A and B. DWI alone had a higher sensitivity for group B (96%) than for group A (71%). The combination of T2-weighted imaging plus DWI plus DCE-MRI provided a sensitivity as high as 100% in group B. The performance of functional imaging sequences for detecting recurrence is different after radical prostatectomy and external-beam radiotherapy. DCE-MRI is a valid and efficient tool to detect prostate cancer recurrence in radical prostatectomy as well as in external-beam radiotherapy. The combination of DCE-MRI and DWI is highly efficient after radiation therapy. Three-dimensional (1)H-MRS needs to be improved. Even though it is not accurate enough, T2-weighted imaging remains essential for the morphologic analysis of the area.

Correlation of pretreatment clinical parameters and PSA nadir after high-intensity focused ultrasound (HIFU) for localised prostate cancer.

PubMed

Ganzer, Roman; Bründl, Johannes; Koch, Daniel; Wieland, Wolf F; Burger, Maximilian; Blana, Andreas

2015-01-01

To determine which pretreatment clinical parameters were predictive of a low prostate-specific antigen (PSA) nadir following high-intensity focused ultrasound (HIFU) treatment. Retrospective study of patients with clinically localised prostate cancer undergoing HIFU at a single centre between December 1997 and September 2009. Whole-gland treatment was applied. Patients also included if they had previously undergone transurethral resection of the prostate (TURP). TURP was also conducted simultaneously to HIFU. Biochemical failure based on Phoenix definition (PSA nadir + 2). Univariate and multivariate analysis of pretreatment clinical parameters conducted to assess those factors predictive of a PSA nadir ≤0.2 and >0.2 ng/ml. Mean (SD) follow-up was 6.2 (2.8) years; median (range) was 6.3 (1.1-12.2) years. Kaplan-Meier estimate of biochemical disease-free survival rate at 8 years was 83 and 48 % for patients achieving a PSA nadir of ≤0.2 and >0.2 ng/ml, respectively. Prostate volume and incidental finding of cancer were significant predictors of low PSA nadir (≤0.2 ng/ml). Prostate volume and incidental finding of cancer could be predictors for oncologic success of HIFU based on post-treatment PSA nadir.

Comparison of cell cycle progression score with two immunohistochemical markers (PTEN and Ki-67) for predicting outcome in prostate cancer after radical prostatectomy.

PubMed

Léon, Priscilla; Cancel-Tassin, Geraldine; Drouin, Sara; Audouin, Marie; Varinot, Justine; Comperat, Eva; Cathelineau, Xavier; Rozet, François; Vaessens, Christophe; Stone, Steven; Reid, Julia; Sangale, Zaina; Korman, Patrick; Rouprêt, Morgan; Fromond-Hankard, Gaelle; Cussenot, Olivier

2018-04-20

Previous studies of the cell cycle progression (CCP) score in surgical specimens of prostate cancer (PCa) in patients treated by radical prostatectomy (RP) demonstrated significant association with time to biochemical recurrence (BCR). In this study, we compared the ability of the CCP score and the expression of PTEN or Ki-67 to predict BCR in a cohort of patients treated by RP. Finally, we constructed the best predictive model for BCR, incorporating biomarkers and relevant clinical variables. The study population consisted of 652 PCa patients enrolled in a retrospective cohort and who had RP surgery in French urological centers from 2000 to 2007. Among the 652 patients with CCP scores and complete clinical data, BCR events occurred in 41%, and the median time from surgery to the last follow-up among BCR-free patients was 72 months. In univariate Cox analysis, the continuous CCP score and positive Ki-67 predicted recurrence with a HR of 1.44 (95% CI 1.17-1.75; p = 5.3 × 10 -4 ) and 1.89 (95% CI 1.38-2.57; p = 1.6 × 10 -4 ), respectively. In contrast, PTEN expression was not associated with BCR risk. Of the three biomarkers, only the CCP score remained significantly associated in a multivariable Cox model (p = 0.026). The best model incorporated CAPRA-S and CCP scores as predictors, with HRs of 1.32 and 1.24, respectively. The CCP score was superior to the two IHC markers (PTEN and Ki-67) for predicting outcome in PCa after RP.

(68)Ga-PSMA-11 dynamic PET/CT imaging in biochemical relapse of prostate cancer.

PubMed

Sachpekidis, C; Eder, M; Kopka, K; Mier, W; Hadaschik, B A; Haberkorn, U; Dimitrakopoulou-Strauss, A

2016-07-01

We aim to investigate the pharmacokinetics and distribution of the recently clinically introduced radioligand (68)Ga-PSMA-11 in men with recurrent prostate cancer (PC) by means of dynamic and whole-body PET/CT. The correlation between PSA levels and (68)Ga-PSMA-11 PET parameters is also investigated. 31 patients with biochemical failure after primary PC treatment with curative intent (median age 71.0 years) were enrolled in the analysis. The median PSA value was 2.0 ng/mL (range = 0.1 - 130.0 ng/mL) and the median Gleason score was 7 (range = 5 - 9). 8/31 (25.8 %) of the included patients had a PSA value < 0.5 ng/ml. All patients underwent dynamic PET/CT (dPET/CT) scanning (60 min) of the pelvis and lower abdomen as well as whole-body PET/CT with (68)Ga-PSMA-11. dPET/CT assessment was based on qualitative evaluation, SUV calculation, and quantitative analysis based on a two-tissue compartment model and a non-compartmental approach leading to the extraction of fractal dimension (FD). 22/31 patients (71.0 %) were (68)Ga-PSMA-11-positive, while 9/31 (29.0 %) patients were (68)Ga-PSMA-11-negative. The median PSA value in the (68)Ga-PSMA-11-positive group was significantly higher (median = 2.35 ng/mL; range = 0.19 - 130.0 ng/mL) than in the (68)Ga-PSMA-11-negative group (median value: 0.34 ng/mL; range = 0.10 - 4.20 ng/mL). A total of 76 lesions were semi-quantitatively evaluated. PC recurrence-associated lesions demonstrated a mean SUVaverage = 12.4 (median = 9.0; range = 2.2 - 84.5) and mean SUVmax = 18.8 (median = 14.1; range = 3.1 - 120.3). Dynamic PET/CT studies of the pelvis revealed the following mean values for the PC recurrence-suspicious lesions: K1 = 0.26, k3 = 0.30, influx = 0.14 and FD = 1.24. Time-activity curves derived from PC-recurrence indicative lesions revealed an increasing (68)Ga-PSMA-11 accumulation during dynamic PET acquisition. Correlation analysis revealed a moderate, but significant, correlation between PSA levels and the number of lesions detected on (68)Ga-PSMA-11 PET/CT (r = 0.54) and between PSA levels and SUVaverage (r = 0.48) or SUVmax (r = 0.44). Ga-PSMA-11 PET/CT demonstrated an overall detection rate of 71.0 % 60 min p.i. of the radiotracer in a mixed patient population with respect to PSA levels and including patients with very low PSA values. Higher PSA values were associated with a higher detection rate. The tracer uptake in PC-recurrence-indicative lesions is increasing during the 60 minutes of dynamic PET acquisition.

PSA kinetics following primary focal cryotherapy (hemiablation) in organ-confined prostate cancer patients.

PubMed

Kongnyuy, Michael; Islam, Shahidul; Mbah, Alfred K; Halpern, Daniel M; Werneburg, Glenn T; Kosinski, Kaitlin E; Chen, Connie; Habibian, David J; Schiff, Jeffrey T; Corcoran, Anthony T; Katz, Aaron E

2018-02-01

We aim to evaluate prostate-specific antigen (PSA) trends in post-primary focal cryotherapy (PFC) patients. This was an institutional review board-approved retrospective study of PFC patients from 2010 to 2015. Patients with at least one post-PFC PSA were included in the study. Biochemical recurrence (BCR) was determined using the Phoenix criteria. PSA bounce was also assessed. We analyzed rates of change of PSA over time of post-PFC between BCR and no BCR groups. PSA-derived variables were analyzed as potential predictors of BCR. A total of 104 PFC patients were included in our analysis. Median (range) age and follow-up time were 66 (48-82) years and 19 (6.3-38.6) months, respectively. Four (3.8%) patients experienced PSA bounce. The median percent drop in first post-PFC PSA of 80.0% was not associated with BCR (p = 0.256) and may indicate elimination of the index lesion. The rate of increase of PSA in BCR patients was significantly higher compared to patients who did not recur (median PSA velocity (PSAV): 0.15 vs 0.04 ng/ml/month, p = 0.001). Similar to PSAV (HR 9.570, 95% CI 3.725-24.592, p < 0.0001), PSA nadir ≥ 2 ng/ml [HR (hazard ratio) 1.251, 95% CI 1.100-1.422, p = 0.001] was independently associated with BCR. A significant drop in post-PFC PSA may indicate elimination of the index lesion. Patients who are likely to recur biochemically have a significantly higher PSAV compared to those who do not recur. Nadir PSA of less than 2 ng/ml may be considered the new normal PSA in focal cryotherapy (hemiablation) follow-up.

Imaging of prostate cancer with PET/CT using 18F-Fluorocholine

PubMed Central

Vali, Reza; Loidl, Wolfgang; Pirich, Christian; Langesteger, Werner; Beheshti, Mohsen

2015-01-01

While 18F-Fluorodeoxyglucose (18F-FDG) Positron-Emission Tomography (PET) has limited value in prostate cancer (PCa), it may be useful for specific subgroups of PCa patients with hormone-resistant poorly differentiated cell types. 18F-Fluorocholine (18F-FCH) PET/CT has been increasingly used in primary and recurrent PCa and has been shown to add valuable information. Although there is a correlation between the foci of activity and the areas of malignancy in the prostate gland, the clinical value of 18F-FCH is still controversial for detection of the malignant focus in the prostate. For the T-staging of PCa at diagnosis the value of 18F-FCH is limited. This is probably due to limited resolution of PET system and positive findings in benign prostate diseases. Conversely, 18F-FCH PET/CT is a promising imaging modality for the delineation of local and distant nodal recurrence and bone metastases and is poised to have an impact on therapy management. In this review, recent studies of 18F-FCH PET/CT in PCa are summarized. PMID:25973332

Laparoscopic and robot-assisted vs open radical prostatectomy for the treatment of localized prostate cancer: a Cochrane systematic review.

PubMed

Ilic, Dragan; Evans, Sue M; Allan, Christie Ann; Jung, Jae Hung; Murphy, Declan; Frydenberg, Mark

2018-06-01

To determine the effects of laparoscopic radical prostatectomy (LRP), or robot-assisted radical prostatectomy (RARP) compared with open radical prostatectomy (ORP) in men with localized prostate cancer. We performed a comprehensive search using multiple databases (CENTRAL, MEDLINE, EMBASE) and abstract proceedings, with no restrictions on the language of publication or publication status, up until 9 June 2017. We included all randomized or pseudo-randomized controlled trials that directly compared LRP and RARP with ORP. Two review authors independently examined full-text reports, identified relevant studies, assessed the eligibility of studies for inclusion, extracted data and assessed risk of bias. We performed statistical analyses using a random-effects model and assessed the quality of the evidence according to Grading of Recommendations Assessment, Development and Evaluation (GRADE). The primary outcomes were prostate cancer-specific survival, urinary quality of life and sexual quality of life. Secondary outcomes were biochemical recurrence-free survival, overall survival, overall surgical complications, serious postoperative surgical complications, postoperative pain, hospital stay and blood transfusions. We included two unique studies in a total of 446 randomized participants with clinically localized prostate cancer. All available outcome data were short-term (up to 3 months). We found no study that addressed the outcome of prostate cancer-specific survival. Based on one trial, RARP probably results in little to no difference in urinary quality of life (mean difference [MD] -1.30, 95% confidence interval [CI] -4.65 to 2.05; moderate quality of evidence) and sexual quality of life (MD 3.90, 95% CI: -1.84 to 9.64; moderate quality of evidence). No study addressed the outcomes of biochemical recurrence-free survival or overall survival. Based on one trial, RARP may result in little to no difference in overall surgical complications (risk ratio [RR] 0.41, 95% CI: 0.16-1.04; low quality of evidence) or serious postoperative complications (RR 0.16, 95% CI: 0.02-1.32; low quality of evidence). Based on two studies, LRP or RARP may result in a small, possibly unimportant improvement in postoperative pain at 1 day (MD -1.05, 95% CI: -1.42 to -0.68; low quality of evidence) and up to 1 week (MD -0.78, 95% CI: -1.40 to -0.17; low quality of evidence). Based on one study, RARP probably results in little to no difference in postoperative pain at 12 weeks (MD 0.01, 95% CI: -0.32 to 0.34; moderate quality of evidence). Based on one study, RARP probably reduces the length of hospital stay (MD -1.72, 95% CI: -2.19 to -1.25; moderate quality of evidence). Based on two studies, LRP or RARP may reduce the frequency of blood transfusions (RR 0.24, 95% CI: 0.12-0.46; low quality of evidence). Assuming a baseline risk for a blood transfusion to be 8.9%, LRP or RARP would result in 68 fewer blood transfusions per 1,000 men (95% CI: 78-48 fewer). There is no evidence to inform the comparative effectiveness of LRP or RARP compared with ORP for oncological outcomes. Urinary and sexual quality of life appear similar. Overall and serious postoperative complication rates appear similar. The difference in postoperative pain may be minimal. Men undergoing LRP or RARP may have a shorter hospital stay and receive fewer blood transfusions. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Targeted Elimination of PCDH-PC Expressing Prostate Cancer Cells for Control of Hormone-Resistant Prostate Cancer

DTIC Science & Technology

2008-11-01

or antisense oligonucleotides ( ASOs ) might be useful in preventing the development of castration- recurrent prostate cancer in prostate cancer...patients. To this end, we have created functional shRNA vectors and ASOs capable of suppressing PCDH-PC expression and we have also created a monoclonal...electrophoresed on an SDS-PAGE gel and blotted onto a filter. The filter was probed with an anti-myc antibody. The levels of myc-tagged PCDH-PC protein

Targeted Elimination of PCDH-PC Expressing Prostate Cancer Cells for Control of Hormone-Resistant Prostate Cancer

DTIC Science & Technology

2009-11-01

expression knockout by shRNAs or antisense oligonucleotides ( ASOs ) might be useful in preventing the development of castration-recurrent prostate...cancer in prostate cancer patients. To this end, we have created functional shRNA vectors and ASOs capable of suppressing PCDH-PC expression and we have...containing PCDH-PC cDNA. Cell extracts were prepared 48 hrs after co-transfection and were electrophoresed on an SDS-PAGE gel and blotted onto a

A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591 in Patients With High-Risk Castrate Biochemically Relapsed Prostate Cancer

DTIC Science & Technology

2015-09-01

Award Number: W81XWH-09-1-0596 TITLE: A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti- PSMA Monoclonal Antibody J591 in Patients With High...1-0596 A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti- PSMA Monoclonal Antibody J591 in Patients With High-Risk Castrat Biochemically Relapsed...in December 2014 with approval to proceed without modifications. 15. SUBJECT TERMS Prostate cancer, PSA, PSMA , monoclonal antibody

Is Ki67 prognostic for aggressive prostate cancer? A multicenter real-world study.

PubMed

Fantony, Joseph J; Howard, Lauren E; Csizmadi, Ilona; Armstrong, Andrew J; Lark, Amy L; Galet, Colette; Aronson, William J; Freedland, Stephen J

2018-06-15

To test if Ki67 expression is prognostic for biochemical recurrence (BCR) after radical prostatectomy (RP). Ki67 immunohistochemistry was performed on tissue microarrays constructed from specimens obtained from 464 men undergoing RP at the Durham and West LA Veterans Affairs Hospitals. Hazard ratios (HR) for Ki67 expression and time to BCR were estimated using Cox regression. Ki67 was associated with more recent surgery year (p < 0.001), positive margins (p = 0.001) and extracapsular extension (p < 0.001). In center-stratified analyses, the adjusted HR for Ki67 expression and BCR approached statistical significance for west LA (HR: 1.54; p = 0.06), but not Durham (HR: 1.10; p = 0.74). This multi-institutional 'real-world' study provides limited evidence for the prognostic role of Ki67 in predicting outcome after RP.

The molecular biology of prostate cancer: current understanding and clinical implications.

PubMed

Gandhi, Jason; Afridi, Adil; Vatsia, Sohrab; Joshi, Gargi; Joshi, Gunjan; Kaplan, Steven A; Smith, Noel L; Khan, Sardar Ali

2018-04-01

With continuous progress over the past few decades in understanding diagnosis, treatment, and genetics, much has been learned about the prostate cancer-diagnosed genome. A comprehensive MEDLINE® and Google scholar literature search was conducted using keyword variations relating to the genetics of prostate cancer such as chromosomal alterations, androgen receptor, castration-resistant, inheritance, polymorphisms, oncogenes, metastasis, biomarkers, and immunotherapy. Traditionally, androgen receptors (AR) have been the focus of research. Recently, identification of recurrent chromosomal alterations that lead to either multiplication of regions (gain-of-function) or deletion of regions (loss-of-function) has opened the door to greater genetic accessibility. These chromosomal aberrations lead to variation in copy number and gene expression. Some of these chromosomal alterations are inherited, while others undergo somatic mutations during disease progression. Inherited gene mutations that make one susceptible to prostate cancer have been identified with familial-linked studies. Somatic genes that progress tumorigenesis have also been identified. Research on the molecular biology of prostate cancer has characterized these genes into tumor suppressor genes or oncogenes. Additionally, genome-wide assay studies have identified many high-risk single-nucleotide polymorphisms recurrent throughout the prostate cancer-diagnosed genome. Castration-resistant prostate cancer is the most aggressive form of prostate cancer, and its research has elucidated many types of mutations associated with AR itself, including enhanced expression and amplification, point mutations, and alternative splicing. Understanding the molecular biology of prostate cancer has permitted more accurate identification using advanced biomarkers and therapy for aggressive forms using immunotherapy. An age-related disease, prostate cancer commands profound attention. With increasing life expectancy and the continuous pursuit of it, prostate cancer is a powerful obstacle best defeated using targeted therapies specifically designed for the unique molecular profile of the malignancy.

Serum/glucocorticoid-regulated kinase 1 expression in primary human prostate cancers.

PubMed

Szmulewitz, Russell Z; Chung, Elizabeth; Al-Ahmadie, Hikmat; Daniel, Silver; Kocherginsky, Masha; Razmaria, Aria; Zagaja, Gregory P; Brendler, Charles B; Stadler, Walter M; Conzen, Suzanne D

2012-02-01

Serum/glucocorticoid-regulated kinase 1 (SGK1), a known target of the androgen receptor (AR) and glucocorticoid receptor (GR), is reported to enhance cell survival. This study sought to better define the role of SGK1 and GR in prostate cancer. Immunohistochemistry was performed for AR, GR, and SGK1 on primary prostate cancers (n = 138) and 18 prostate cancers from patients treated with androgen deprivation therapy. Relative staining intensity was compared utilizing a Fisher's exact test. Univariate analyses were performed using log-rank and chi-squared tests to evaluate prostate cancer recurrence with respect to SGK1 expression. SGK1 expression was strong (3+) in 79% of untreated cancers versus 44% in androgen-deprived cancers (P = 0.003). Conversely, GR expression was present in a higher proportion of androgen-deprived versus untreated cancers (78% vs. 38%, P = 0.002). High-grade cancers were nearly twice as likely to have relatively low (0 to 2+) SGK1 staining compared to low-grade cancers (13.8% vs. 26.5%, P = 0.08). Low SGK1 expression in untreated tumors was associated with increased risk of cancer recurrence (adjusted log-rank test P = 0.077), 5-year progression-free survival 47.8% versus 72.6% (P = 0.034). SGK1 expression is high in most untreated prostate cancers and declines with androgen deprivation. However, these data suggest that relatively low expression of SGK1 is associated with higher tumor grade and increased cancer recurrence, and is a potential indicator of aberrant AR signaling in these tumors. GR expression increased with androgen deprivation, potentially providing a mechanism for the maintenance of androgen pathway signaling in these tumors. Further study of the AR/GR/SGK1 network in castration resistance. Copyright © 2011 Wiley Periodicals, Inc.

Morbidity and prostate-specific antigen control of external beam radiation therapy plus low-dose-rate brachytherapy boost for low, intermediate, and high-risk prostate cancer.

PubMed

Koontz, Bridget F; Chino, Junzo; Lee, W Robert; Hahn, Carol A; Buckley, Niall; Huang, Samuel; Kim, Jay; Reagan, Robert; Joyner, Raymond; Anscher, Mitchell S

2009-01-01

Dose escalation has been shown beneficial in prostate cancer. Brachytherapy (BT) provides an opportunity for dose escalation beyond what can be safely delivered using only teletherapy methods. The purpose of this study was to determine cancer control and morbidity of external beam radiation therapy (EBRT) plus low-dose-rate (LDR) BT boost in patients with prostate cancer treated at Duke University Health System. Between June 1997 and August 2007, 199 patients were consecutively treated at our facility with 46Gy EBRT followed by 100Gy palladium-103 ((103)Pd) or 120Gy iodine-125 ((125)I) LDR prostate implant. Treatment characteristics and followup data were retrospectively analyzed. Intermediate risk was defined as T2b-c, Gleason score 7 (GS 7), or prostate-specific antigen (PSA) of 10.1-19.9ng/mL. High risk was defined as GS 8-10, PSA>20, T3+, or two intermediate risk factors. The Radiation Therapy Oncology Group toxicity scale was used to report morbidity for gastrointestinal (GI) and genitourinary (GU) effects. PSA recurrence was defined as nadir+2ng/mL. Median followup was 4.2 years for all patients, 4.8 years for high-risk patients. Risk categories were as follows: 20% low risk, 47% intermediate risk, and 33% high risk. Forty five percent of patients received adjuvant androgen deprivation therapy (ADT). The median length of time since end of ADT to last followup was 2.7 years in all patients, 2.0 years for high-risk patients. Five-year biochemical relapse-free survival was 87% for all, 81% for high-risk patients. PSA control was similar at 92% for all and 86% for high-risk patients. Five-year actuarial risk of any and Grade 3 late GI morbidity was 38% and 7% respectively, and any and Grade 3 late GU morbidity was 21% and 3%, respectively. There were no significant differences in risk of Grade 2+GI or GU morbidity with choice of isotope. EBRT plus LDR BT has acceptable morbidity and, with 5-year followup, provides excellent cancer control even in high-risk patients.

Prostate cancer in young adults-Seventeen-year clinical experience of a single center.

PubMed

Huang, Tzu-Hao; Kuo, Junne-Yih; Huang, Yi-Hsiu; Chung, Hsiao-Jen; Huang, William J S; Wu, Howard H H; Chang, Yen-Hwa; Lin, Alex T L; Chen, Kuang-Kuo

2017-01-01

In the general population, prostate adenocarcinoma affects predominately older men. If fact, most current guidelines suggest that males over the age of 50 years should undergo prostate cancer screening. However, the clinical behavior and prognosis of prostate cancer in young adults is not well defined. The aim of this study was to evaluate the clinical behavior, pathological characteristics, and prognosis of prostate cancer in young adults. We retrospectively reviewed the records of young patients (age, ≤50 years) in our hospital with prostate adenocarcinoma between 1997 and 2013. We compared data including initial presentation, cancer cell type, Gleason score, disease stage, prostate-specific antigen (PSA) level, prostate volume, treatment, and survival between patients both younger and older than 50 years. Data were analyzed using the Kaplan-Meier method to assess survival. Twenty-six patients were enrolled in our study, accounting for 0.55% of all patients with a diagnosis of prostate cancer at our facility. All 26 patients had a pathology diagnosis of adenocarcinoma, with a mean age on diagnosis of 46.8±2.8 years (range, 39-50 years). On initial presentation, patients older than 50 years more frequently displayed lower urinary tract symptoms (LUTS) than younger patients (62.3% vs. 30.4%, p=0.008). There was no statistical difference in histological grade, disease stage, PSA level, overall survival, and biochemical-free survival between the two groups. The result of our investigation indicated that prostate adenocarcinoma patients younger than 50 years had similar histological grade, disease stage, PSA level, overall survival, and biochemical-free survival as the older population. However, patients younger than 50 years with prostate cancer less frequently showed initial symptoms of LUTS. Copyright © 2016. Published by Elsevier Taiwan LLC.

Safety and Efficacy of Robot-assisted Radical Prostatectomy in a Low-volume Center: A 6-year Single-surgeon Experience.

PubMed

DI Pierro, Giovanni Battista; Grande, Pietro; Mordasini, Livio; Danuser, Hansjörg; Mattei, Agostino

2016-08-01

To analyze safety and efficacy of robot-assisted radical prostatectomy (RARP) in a low-volume centre. From 2008 to 2015, 400 consecutive patients undergoing RARP were prospectively enrolled. Complications were classified according to the Modified Clavien System. Biochemical recurrence (BCR) was defined as two consecutive prostate-specific antigen (PSA) values ≥0.2 ng/ml. Functional outcomess were assessed using validated, self-administered questionnaires. Median patient age was 64.5 years. Mean standard deviation (SD) preoperative PSA level was 11.3 (11.7) ng/ml. Median interquartile range (IQR) follow-up was 36 (12-48) months. Overall complication rate was 27.7% (minor complications rate 16.2%). Overall 1-, 3- and 6-year BCR-free survival rates were 85.7%, 77.5% and 53.9%, respectively; these rates were 94.1%, 86.2% and 70.1% in pT2 diseases. At follow-up, 98.4% of patients were fully continent (median (IQR) time to continence was 2 (1-3) months) and 68.2% were potent (median (IQR) time to potency of 3 (3-4) months). RARP appears to be a valuable option for treating clinically localised prostate cancer also in a low-volume institution. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

PSMA PET in prostate cancer – a step towards personalized medicine

PubMed Central

Bouchelouche, Kirsten; Choyke, Peter L.

2017-01-01

Purpose of review Increasing attention is being given to personalized medicine in oncology, where therapies are tailored to the particular characteristics of the individual cancer patient. In recent years, there has been greater focus on PSMA in prostate cancer (PCa) as a target for imaging and therapy with radionuclides. This review highlights the recent advancements in PSMA PET in PCa during the past year. Recent findings Several reports on PSMA PET/CT in PCa patients are demonstrating promising results, especially for detection of biochemical recurrence. 18F-PSMA PET/CT may be superior to 68Ga-PSMA PET/CT. The detection rate of PSMA PET is influenced by PSA level. PSMA PET/CT may have a higher detection rate than choline PET/CT. Only a few reports have been published on PSMA PET/MRI, and this modality remains to be elucidated further. Conclusion Molecular imaging with PSMA PET is paving the way for personalized medicine in PCa. However, large prospective clinical studies are needed to further evaluate the role of PSMA PET/CT and PET/MRI in the clinical workflow of PCa. PSMA is an excellent target for imaging and therapy with radionuclides, and the “image and treat” strategy has the potential to become a milestone in the management of PCa patients. PMID:26967720

DOE Office of Scientific and Technical Information (OSTI.GOV)

Turaka, Aruna; Buyyounouski, Mark K., E-mail: mark.buyyounouski@fccc.edu; Hanlon, Alexandra L.

Purpose: To correlate tumor oxygenation status with long-term biochemical outcome after prostate brachytherapy. Methods and Materials: Custom-made Eppendorf PO{sub 2} microelectrodes were used to obtain PO{sub 2} measurements from the prostate (P), focused on positive biopsy locations, and normal muscle tissue (M), as a control. A total of 11,516 measurements were obtained in 57 men with localized prostate cancer immediately before prostate brachytherapy was given. The Eppendorf histograms provided the median PO{sub 2}, mean PO{sub 2}, and % <5 mm Hg or <10 mm Hg. Biochemical failure (BF) was defined using both the former American Society of Therapeutic Radiation Oncologymore » (ASTRO) (three consecutive raises) and the current Phoenix (prostate-specific antigen nadir + 2 ng/mL) definitions. A Cox proportional hazards regression model evaluated the influence of hypoxia using the P/M mean PO{sub 2} ratio on BF. Results: With a median follow-up time of 8 years, 12 men had ASTRO BF and 8 had Phoenix BF. On multivariate analysis, P/M PO{sub 2} ratio <0.10 emerged as the only significant predictor of ASTRO BF (p = 0.043). Hormonal therapy (p = 0.015) and P/M PO{sub 2} ratio <0.10 (p = 0.046) emerged as the only independent predictors of the Phoenix BF. Kaplan-Meier freedom from BF for P/M ratio <0.10 vs. {>=}0.10 at 8 years for ASTRO BF was 46% vs. 78% (p = 0.03) and for the Phoenix BF was 66% vs. 83% (p = 0.02). Conclusions: Hypoxia in prostate cancer (low mean P/M PO{sub 2} ratio) significantly predicts for poor long-term biochemical outcome, suggesting that novel hypoxic strategies should be investigated.« less

Common Genetic Variation in CYP17A1 and Response to Abiraterone Acetate in Patients with Metastatic Castration-Resistant Prostate Cancer

PubMed Central

Binder, Moritz; Zhang, Ben Y.; Hillman, David W.; Kohli, Rhea; Kohli, Tanvi; Lee, Adam; Kohli, Manish

2016-01-01

Treatment with abiraterone acetate and prednisone (AA/P) prolongs survival in metastatic castration-resistant prostate cancer (mCRPC) patients. We evaluated the genetic variation in CYP17A1 as predictive of response to AA/P. A prospective collection of germline DNA prior to AA/P initiation and follow-up of a mCRPC cohort was performed. Five common single-nucleotide polymorphisms (SNPs) in CYP17A1 identified using a haplotype-based tagging algorithm were genotyped. Clinical outcomes included biochemical response and time to biochemical progression on AA/P. Logistic regression was used to assess the association between tag SNPs and biochemical response. Proportional hazards regression was used to assess the association between tag SNPs and time to biochemical progression. Odds or hazard ratio per minor allele were estimated and p-values below 0.05 were considered statistically significant. Germline DNA was successfully genotyped for four tag SNPs in 87 patients. The median age was 73 years (54–90); the median prostate-specific antigen was 66 ng/dL (0.1–99.9). A single SNP, rs2486758, was associated with lower odds of experiencing a biochemical response (Odds ratio 0.22, 95% confidence interval 0.07–0.63, p = 0.005) and a shorter time to biochemical progression (Hazard ratio 2.23, 95% confidence interval 1.39–3.56, p < 0.001). This tag SNP located in the promoter region of CYP17A1 will need further validation as a predictive biomarker for AA/P therapy. PMID:27409606

Configurations of a two-tiered amplified gene expression system in adenoviral vectors designed to improve the specificity of in vivo prostate cancer imaging

PubMed Central

Sato, M; Figueiredo, ML; Burton, JB; Johnson, M; Chen, M; Powell, R; Gambhir, SS; Carey, M; Wu, L

2009-01-01

Effective treatment for recurrent, disseminated prostate cancer is notably limited. We have developed adenoviral vectors with a prostate-specific two-step transcriptional amplification (TSTA) system that would express therapeutic genes at a robust level to target metastatic disease. The TSTA system employs the prostate-specific antigen (PSA) promoter/enhancer to drive a potent synthetic activator, which in turn activates the expression of the therapeutic gene. In this study, we explored different configurations of this bipartite system and discovered that physical separation of the two TSTA components into E1 and E3 regions of adenovirus was able to enhance androgen regulation and cell-discriminatory expression. The TSTA vectors that express imaging reporter genes were assessed by noninvasive imaging technologies in animal models. The improved selectivity of the E1E3 configured vector was reflected in silenced ectopic expression in the lung. Significantly, the enhanced specificity of the E1E3 vector enabled the detection of lung metastasis of prostate cancer. An E1E3 TSTA vector that expresses the herpes simplex virus thymidine kinase gene can effectively direct positron emission tomography (PET) imaging of the tumor. The prostate-targeted gene delivery vectors with robust and cell-specific expression capability will advance the development of safe and effective imaging guided therapy for recurrent metastatic stages of prostate cancer. PMID:18305574

Detection of Recurrent Prostate Carcinoma with anti-1-Amino-3-18F-Fluorocyclobutane-1-Carboxylic Acid PET/CT and 111In–Capromab Pendetide SPECT/CT

PubMed Central

Savir-Baruch, Bital; Nieh, Peter T.; Master, Viraj A.; Halkar, Raghuveer K.; Rossi, Peter J.; Lewis, Melinda M.; Nye, Jonathon A.; Yu, Weiping; Bowman, F. DuBois; Goodman, Mark M.

2011-01-01

Purpose: To compare the diagnostic performance of the synthetic amino acid analog radiotracer anti-1-amino-3-fluorine 18-fluorocyclobutane-1-carboxylic acid (anti-3-18F-FACBC) with that of indium 111 (111In)–capromab pendetide in the detection of recurrent prostate carcinoma. Materials and Methods: This prospective study was approved by the institutional review board and complied with HIPAA guidelines. Written informed consent was obtained. Fifty patients (mean age, 68.3 years ± 8.1 [standard deviation]; age range, 50–90 years) were included in the study on the basis of the following criteria: (a) Recurrence of prostate carcinoma was suspected after definitive therapy for localized disease, (b) bone scans were negative, and (c) anti-3-18F-FACBC positron emission tomography (PET)/computed tomography (CT) and 111In–capromab pendetide single photon emission computed tomography (SPECT)/CT were performed within 6 weeks of each other. Studies were evaluated by two experienced interpreters for abnormal uptake suspicious for recurrent disease in the prostate bed and extraprostatic locations. The reference standard was a combination of tissue correlation, imaging, laboratory, and clinical data. Diagnostic performance measures were calculated and tests of the statistical significance of differences determined by using the McNemar χ2 test as well as approximate tests based on the difference between two proportions. Results: For disease detection in the prostate bed, anti-3-18F-FACBC had a sensitivity of 89% (32 of 36 patients; 95% confidence interval [CI]: 74%, 97%), specificity of 67% (eight of 12 patients; 95% CI: 35%, 90%), and accuracy of 83% (40 of 48 patients; 95% CI: 70%, 93%). 111In–capromab pendetide had a sensitivity of 69% (25 of 36 patients; 95% CI: 52%, 84%), specificity of 58% (seven of 12 patients; 95% CI: 28%, 85%), and accuracy of 67% (32 of 48 patients; 95% CI: 52%, 80%). In the detection of extraprostatic recurrence, anti-3-18F-FACBC had a sensitivity of 100% (10 of 10 patients; 95% CI: 69%, 100%), specificity of 100% (seven of seven patients; 95% CI: 59%, 100%), and accuracy of 100% (17 of 17 patients; 95% CI: 80%, 100%). 111In–capromab pendetide had a sensitivity of 10% (one of 10 patients; 95% CI: 0%, 45%), specificity of 100% (seven of seven patients; 95% CI: 59%, 100%), and accuracy of 47% (eight of 17 patients; 95% CI: 23%, 72%). Conclusion: anti-3-18F-FACBC PET/CT was more sensitive than 111In–capromab pendetide SPECT/CT in the detection of recurrent prostate carcinoma and is highly accurate in the differentiation of prostatic from extraprostatic disease. © RSNA, 2011 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11102023/-/DC1 PMID:21493787

How to diagnose and treat focal therapy failure and recurrence?

PubMed

Barret, Eric; Harvey-Bryan, Kadi-Ann; Sanchez-Salas, Rafael; Rozet, Francois; Galiano, Marc; Cathelineau, Xavier

2014-05-01

Focal therapy presents an alternative option for disease-targeted therapy while preserving erectile and urinary function without compromising oncological outcome. Such treatment, which preserves normal prostate parenchyma, presents a clinical challenge to the urologist, as typical disease surveillance parameters are not as reliable in post-ablation follow-up. We propose an integrated approach to post-ablation surveillance to identify treatment failure as well as recurrence. Post-ablation prostate-specific antigen kinetics, imaging based on multiparametric MRI and control biopsies are the tools currently used to follow patients after focal therapy. Good treatment response is indicated by a negative control biopsy, absence of persistent lesion on post-treatment imaging and a reduction in prostate-specific antigen of at least 50%. When histological evidence of therapeutic failure or recurrence is present, different options of management may be proposed to the patient including active surveillance, focal salvage therapy or radical salvage treatment, depending on the characteristics of the lesion found. A recommended post-ablation surveillance protocol is presented as well as a discussion of management strategies based on the data currently available.

Evaluation of ERG and SPINK1 by Immunohistochemical Staining and Clinicopathological Outcomes in a Multi-Institutional Radical Prostatectomy Cohort of 1067 Patients.

PubMed

Brooks, James D; Wei, Wei; Hawley, Sarah; Auman, Heidi; Newcomb, Lisa; Boyer, Hilary; Fazli, Ladan; Simko, Jeff; Hurtado-Coll, Antonio; Troyer, Dean A; Carroll, Peter R; Gleave, Martin; Lance, Raymond; Lin, Daniel W; Nelson, Peter S; Thompson, Ian M; True, Lawrence D; Feng, Ziding; McKenney, Jesse K

2015-01-01

Distinguishing between patients with early stage, screen detected prostate cancer who must be treated from those that can be safely watched has become a major issue in prostate cancer care. Identification of molecular subtypes of prostate cancer has opened the opportunity for testing whether biomarkers that characterize these subtypes can be used as biomarkers of prognosis. Two established molecular subtypes are identified by high expression of the ERG oncoprotein, due to structural DNA alterations that encode for fusion transcripts in approximately ½ of prostate cancers, and over-expression of SPINK1, which is purportedly found only in ERG-negative tumors. We used a multi-institutional prostate cancer tissue microarray constructed from radical prostatectomy samples with associated detailed clinical data and with rigorous selection of recurrent and non-recurrent cases to test the prognostic value of immunohistochemistry staining results for the ERG and SPINK1 proteins. In univariate analysis, ERG positive cases (419/1067; 39%) were associated with lower patient age, pre-operative serum PSA levels, lower Gleason scores (≤ 3+4=7) and improved recurrence free survival (RFS). On multivariate analysis, ERG status was not correlated with RFS, disease specific survival (DSS) or overall survival (OS). High-level SPINK1 protein expression (33/1067 cases; 3%) was associated with improved RFS on univariate and multivariate Cox regression analysis. Over-expression of either protein was not associated with clinical outcome. While expression of ERG and SPINK1 proteins was inversely correlated, it was not mutually exclusive since 3 (0.28%) cases showed high expression of both. While ERG and SPINK1 appear to identify discrete molecular subtypes of prostate cancer, only high expression of SPINK1 was associated with improved clinical outcome. However, by themselves, neither ERG nor SPINK1 appear to be useful biomarkers for prognostication of early stage prostate cancer.

Evaluation of ERG and SPINK1 by Immunohistochemical Staining and Clinicopathological Outcomes in a Multi-Institutional Radical Prostatectomy Cohort of 1067 Patients

PubMed Central

Brooks, James D.; Wei, Wei; Hawley, Sarah; Auman, Heidi; Newcomb, Lisa; Boyer, Hilary; Fazli, Ladan; Simko, Jeff; Hurtado-Coll, Antonio; Troyer, Dean A.; Carroll, Peter R.; Gleave, Martin; Lance, Raymond; Lin, Daniel W.; Nelson, Peter S.; Thompson, Ian M.; True, Lawrence D.; Feng, Ziding; McKenney, Jesse K.

2015-01-01

Distinguishing between patients with early stage, screen detected prostate cancer who must be treated from those that can be safely watched has become a major issue in prostate cancer care. Identification of molecular subtypes of prostate cancer has opened the opportunity for testing whether biomarkers that characterize these subtypes can be used as biomarkers of prognosis. Two established molecular subtypes are identified by high expression of the ERG oncoprotein, due to structural DNA alterations that encode for fusion transcripts in approximately ½ of prostate cancers, and over-expression of SPINK1, which is purportedly found only in ERG-negative tumors. We used a multi-institutional prostate cancer tissue microarray constructed from radical prostatectomy samples with associated detailed clinical data and with rigorous selection of recurrent and non-recurrent cases to test the prognostic value of immunohistochemistry staining results for the ERG and SPINK1 proteins. In univariate analysis, ERG positive cases (419/1067; 39%) were associated with lower patient age, pre-operative serum PSA levels, lower Gleason scores (≤3+4=7) and improved recurrence free survival (RFS). On multivariate analysis, ERG status was not correlated with RFS, disease specific survival (DSS) or overall survival (OS). High-level SPINK1 protein expression (33/1067 cases; 3%) was associated with improved RFS on univariate and multivariate Cox regression analysis. Over-expression of either protein was not associated with clinical outcome. While expression of ERG and SPINK1 proteins was inversely correlated, it was not mutually exclusive since 3 (0.28%) cases showed high expression of both. While ERG and SPINK1 appear to identify discrete molecular subtypes of prostate cancer, only high expression of SPINK1 was associated with improved clinical outcome. However, by themselves, neither ERG nor SPINK1 appear to be useful biomarkers for prognostication of early stage prostate cancer. PMID:26172920

PREDICTORS OF BIOCHEMICAL REMISSION AND RECURRENCE AFTER SURGICAL AND RADIATION TREATMENTS OF CUSHING DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

PubMed

Abu Dabrh, Abd Moain Abu; Singh Ospina, Naykky M; Al Nofal, Alaa; Farah, Wigdan H; Barrionuevo, Patricia; Sarigianni, Maria; Mohabbat, Arya B; Benkhadra, Khalid; Carranza Leon, Barbara G; Gionfriddo, Michael R; Wang, Zhen; Mohammed, Khaled; Ahmed, Ahmed T; Elraiyah, Tarig A; Haydour, Qusay; Alahdab, Fares; Prokop, Larry J; Murad, Mohammad Hassan

2016-04-01

We conducted a systematic review and meta-analysis to synthesize the evidence about predictors that may affect biochemical remission and recurrence after transsphenoidal surgery (TSS), radiosurgery (RS), and radiotherapy (RT) in Cushing disease. We searched multiple databases through December 2014 including original controlled and uncontrolled studies that enrolled patients with Cushing disease who received TSS (first-line), RS, or RT. We extracted data independently, in duplicates. Outcomes of interest were biochemical remission and recurrence. A meta-analysis was conducted using the random-effects model to estimate event rates with 95% confidence intervals (CIs). First-line TSS was associated with high remission (76% [95% CI, 72 to 79%]) and low recurrence rates (10% [95% CI, 6 to 16%]). Remission after TSS was higher in patients with microadenomas or positive-adrenocorticotropic hormone tumor histology. RT was associated with a high remission rate (RS, 68% [95% CI, 61 to 77%]; RT, 66% [95% CI, 58 to 75%]) but also with a high recurrence rate (RS, 32% [95% CI, 16 to 60%]; RT, 26% [95% CI, 14 to 48%]). Remission after RS was higher at short-term follow-up (≤2 years) and with high-dose radiation, while recurrence was higher in women and with lower-dose radiation. Remission was after RT in adults who received TSS prior to RT, and with lower radiation doses. There was heterogeneity (nonstandardization) in the criteria and cutoff points used to define biochemical remission and recurrence. First-line TSS is associated with high remission and low recurrence, while RS and RT are associated with reasonable remission rates but important recurrence rates. The current evidence warrants low confidence due to the noncomparative nature of the studies, high heterogeneity, and imprecision.

Management of Men with Prostate-specific Antigen Failure After Prostate Radiotherapy: The Case Against Early Androgen Deprivation.

PubMed

Brand, Douglas; Parker, Chris

2018-04-01

In men with prostate-specific antigen failure after radical radiotherapy, androgen deprivation therapy should be delayed until the site of recurrence is known to allow consideration of curative treatment options, to delay androgen deprivation therapy-related morbidity, and to enable earlier access to abiraterone and docetaxel. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Bioengineering Multifunctional Quantum Dot-Polypeptide Assemblies and Immunoconjugates for the Ablation of Advanced Prostate Cancer Disease

DTIC Science & Technology

2008-02-01

disease [1]. Localized prostate cancer is generally treated with surgery (radical prostatectomy), radiation therapy, or cryotherapy [2]. However, disease...receiving radical radiotherapy were left with residual disease [3]. Currently, patients with recurrent, locally advanced, or metastatic prostate cancer are...treated by androgen deprivation alone or in combination with local therapy. Although most patients initially respond to androgen deprivation, a large

Prostate-specific acid phosphatase versus acid phosphatase in monitoring patients with prostate cancer.

PubMed

Killian, C S; Vargas, F P; Slack, N H; Murphy, G P; Chu, T M

1982-01-01

Serial levels of PAP and AcP activity were compared for their relative values in monitoring 57 early and 33 advanced prostate cancer patients. Several findings regarding the patients' disease status and the enzyme levels have been observed that may be beneficial to therapeutic management of these patients. They are: [1] an elevated PAP activity in disease recurrence and disease progression generally precedes an elevated AcP activity, and thus represents a more sensitive index for patients with early and advanced disease; [2] serial mean levels of PAP activity greater than the mean + 3 SD are more predictive for disease recurrence and progression than are those of AcP activity in both groups of patients; [3] PAP activity is a more sensitive monitor for changes in objective treatment response than is AcP activity; and [4] PAP is more specific than AcP for prostate, thus offering a more reliable marker to identify metastasis of unknown origin, or to confirm metastasis derived from a primary prostate tumor that may have been suggested by other non-prostate-specific marker[s]. In addition, data suggest a favorable prognosis for patients receiving therapy as inferred by a serial mean of PAP activity that is less than mean + 3 SD.

Personality, treatment choice and satisfaction in patients with localized prostate cancer.

PubMed

Block, Craig A; Erickson, Brad; Carney-Doebbling, Caroline; Gordon, Susanna; Fallon, Bernard; Konety, Badrinath R

2007-11-01

Radical prostatectomy (RP), external beam radiation (XRT) and brachytherapy (BTX) are the most commonly used treatments for localized prostate cancer. We studied whether patient personality influences treatment choice and overall treatment satisfaction. From 1998 to 2002, 219 consecutive patients treated with RP (n = 74), XRT (n = 73), or BTX (n = 72) at our institution who remained free of biochemical recurrence were sent the Big Five Inventory (BFI) and a satisfaction/treatment participation questionnaire. We compared personality, satisfaction and participation scores between the three groups. Correlation between personality and satisfaction was determined. Multivariate regression was used to determine association between personality and satisfaction/participation after controlling for patient- and disease-related factors. Higher mean satisfaction and participation scores were observed within the RP and XRT groups, respectively (P = NS). No significant differences in personality were observed between groups. XRT patients tended to have higher extroversion, openness and agreeability scores, while RP patients tended to be more neurotic and conscientious (all P = NS). After controlling for other factors, a negative correlation was found between openness scores and satisfaction and a positive correlation between conscientiousness scores and satisfaction. Specific personality traits were associated with interest in participation in care for both RP and BTX patients but not for XRT patients. There are mild variations in personality as measured by the BFI between patients undergoing treatment for localized prostate cancer. Certain BFI-measured personality traits may be associated with levels of satisfaction following therapy. Disease concerns and provider recommendations may override the influence of personality in the decision-making process.

Predictive factors of 18F-choline PET/CT positivity in patients with prostate cancer recurrence after radiation therapy: is the impact of PSA nadir underestimated?

PubMed

Johnson, Alison C; Dugué, Audrey Emmanuelle; Silva, Marlon; Moise, Laura; Tillou, Xavier; Joly, Florence; Aide, Nicolas

2016-12-01

The objective of this study is to explore the impact of PSA nadirs on detection rates of prostate cancer (PCa) recurrence with 18 F-choline (CH) PET/CT after external beam radiation therapy (EBRT). In this retrospective study, data were collected from 54 patients with suspicion of PCa biochemical recurrence after EBRT (28 patients treated initially with EBRT and 26 as salvage therapy in the absence of PSA decrease after initial treatment), who underwent 18 F-CH PET/CT between 2010 and 2015. PSA nadir and trigger PSA were collected from patient files. Relative PSA was calculated by subtracting the nadir from the trigger PSA. Median PSA nadir was 0.31 (0.01-13.31) ng/mL, trigger PSA was 7.85 (0.47-111.60) ng/mL, and relative PSA was 6.05 (0.24-104.59) ng/mL. Overall, 40 (74%) PET/CT scans were positive: recurrence was local and/or regional in 29 patients, distant in 15 and combined both in four, with no association between PSA values and sites of recurrence. In univariate analysis, trigger (p = 0.015) and relative (p = 0.0005) PSA values and PSA velocity (p = 0.01) were significantly linked to positive PET/CT, but PSA nadir was not. In subgroup analysis, these significant differences were only found in the salvage EBRT group. Akaike Information Criterion multivariate model comparison found that relative PSA was a better predictor of positive PET/CT than trigger PSA (PSAt). 18 F-CH PET/CT detection rates increased with trigger and relative PSA: 0% (0/4 patients), 71% (5/7 patients), and 81% (35/43 patients) for PSAt <2 ng/mL, 2≤ PSAt ≤4 ng/mL, and PSAt >4 ng/mL, respectively, and 14% (1/7 patients), 50% (5/10 patients), and 92% (34/37 patients) when relative PSA was taken into account instead of trigger PSA, with seven (13%) patients changing subgroups. We found a high overall detection rate and an increase in detection rates proportional to trigger and relative PSAs. Although relative PSA, taking into account PSA nadir, was a better predictive factor of PET/CT positivity in univariate analysis, this was most noticeable for high PSAs. For low PSAs, trigger PSA remains most relevant. Larger series with intermediate PSA values need to be studied to fully apprehend nadir impact.

Lymph node yield during radical prostatectomy does not impact rate of biochemical recurrence in patients with seminal vesicle invasion and node-negative disease.

PubMed

Badani, Ketan K; Reddy, Balaji N; Moskowitz, Eric J; Paulucci, David J; Beksac, Alp Tuna; Martini, Alberto; Whalen, Michael J; Skarecky, Douglas W; Huynh, Linda My; Ahlering, Thomas E

2018-06-01

Seminal vesicle invasion (SVI) is a risk factor for poor oncologic outcome in patients with prostate cancer. Modifications to the pelvic lymph node dissection (PLND) during radical prostatectomy (RP) have been reported to have a therapeutic benefit. The present study is the first to determine if lymph node yield (LNY) is associated with a lower risk of biochemical recurrence (BCR) for men with SVI. A total of 220 patients from 2 high-volume institutions who underwent RP without adjuvant treatment between 1990 and 2015 and had prostate cancer with SVI (i.e., pT3b) were identified, and 21 patients did not undergo lymph node dissection. BCR was defined as a postoperative PSA>0.2ng/mL, or use of salvage androgen deprivation therapy (ADT) or radiation. Multivariable Cox proportional hazards models were used to determine whether LNY was predictive of BCR, controlling for PSA, pathologic Gleason Score, pathologic lymph node status, NCCN risk category, etc. The Kaplan-Meier method was used to determine 3-year freedom from BCR. Median number of lymph nodes sampled were 7 (IQR: 3-12; range: 0-35) and 90.5% underwent PLND. The estimated 3-year BCR rate was 43.9%. Results from multivariable analysis demonstrated that LNY was not significantly associated with risk of BCR overall (HR = 1.00, 95% CI: 0.98-1.03; P = 0.848) for pN0 (HR = 0.99, 95% CI: 0.97-1.03; P = 0.916) or pN1 patients (HR = 0.96, 95% CI: 0.88-1.06; P = 0.468). Overall, PSA (HR = 1.02, P<0.001) and biopsy Gleason sum ≥ 8 (HR = 1.81, P = 0.001) were associated with an increased risk of BCR, and increasing LNY increased the likelihood of detecting>2 positive lymph nodes (OR = 1.27, 95% CI: 1.06-1.65, P = 0.023). Seminal vesicle invasion is associated with an increased risk of BCR at 3 years, primarily due to pathologic Gleason score and PSA. Although greater lymph node yield is diagnostic and facilitates more accurate pathologic staging, our data do not show a therapeutic benefit in reducing BCR. Copyright © 2018 Elsevier Inc. All rights reserved.

Multivariable model development and internal validation for prostate cancer specific survival and overall survival after whole-gland salvage Iodine-125 prostate brachytherapy.

PubMed

Peters, Max; van der Voort van Zyp, Jochem R N; Moerland, Marinus A; Hoekstra, Carel J; van de Pol, Sandrine; Westendorp, Hendrik; Maenhout, Metha; Kattevilder, Rob; Verkooijen, Helena M; van Rossum, Peter S N; Ahmed, Hashim U; Shah, Taimur T; Emberton, Mark; van Vulpen, Marco

2016-04-01

Whole-gland salvage Iodine-125-brachytherapy is a potentially curative treatment strategy for localised prostate cancer (PCa) recurrences after radiotherapy. Prognostic factors influencing PCa-specific and overall survival (PCaSS & OS) are not known. The objective of this study was to develop a multivariable, internally validated prognostic model for survival after whole-gland salvage I-125-brachytherapy. Whole-gland salvage I-125-brachytherapy patients treated in the Netherlands from 1993-2010 were included. Eligible patients had a transrectal ultrasound-guided biopsy-confirmed localised recurrence after biochemical failure (clinical judgement, ASTRO or Phoenix-definition). Recurrences were assessed clinically and with CT and/or MRI. Metastases were excluded using CT/MRI and technetium-99m scintigraphy. Multivariable Cox-regression was used to assess the predictive value of clinical characteristics in relation to PCa-specific and overall mortality. PCa-specific mortality was defined as patients dying with distant metastases present. Missing data were handled using multiple imputation (20 imputed sets). Internal validation was performed and the C-statistic calculated. Calibration plots were created to visually assess the goodness-of-fit of the final model. Optimism-corrected survival proportions were calculated. All analyses were performed according to the TRIPOD statement. Median total follow-up was 78months (range 5-139). A total of 62 patients were treated, of which 28 (45%) died from PCa after mean (±SD) 82 (±36) months. Overall, 36 patients (58%) patients died after mean 84 (±40) months. PSA doubling time (PSADT) remained a predictive factor for both types of mortality (PCa-specific and overall): corrected hazard ratio's (HR's) 0.92 (95% CI: 0.86-0.98, p=0.02) and 0.94 (95% CI: 0.90-0.99, p=0.01), respectively (C-statistics 0.71 and 0.69, respectively). Calibration was accurate up to 96month follow-up. Over 80% of patients can survive 8years if PSADT>24months (PCaSS) and >33months (OS). Only approximately 50% survival is achieved with a PSADT of 12months. A PSADT of respectively >24months and >33months can result in >80% probability of PCa- specific and overall survival 8years after whole-gland salvage I-125-brachytherapy. Survival should be weighed against toxicity from a salvage procedure. Larger series and external validation are necessary. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

64Cu-PSMA-617 PET/CT Imaging of Prostate Adenocarcinoma: First In-Human Studies.

PubMed

Grubmüller, Bernhard; Baum, Richard P; Capasso, Enza; Singh, Aviral; Ahmadi, Yasaman; Knoll, Peter; Floth, Andreas; Righi, Sergio; Zandieh, Shahin; Meleddu, Carlo; Shariat, Shahrokh F; Klingler, Hans Christoph; Mirzaei, Siroos

2016-10-07

The prostate-specific membrane antigen (PSMA) is a cell surface protein, which is overexpressed in nearly all cases of prostate cancer (PCa). PET imaging with 68 Ga-PSMA-HBED-CC has recently found widespread application in the diagnosis of recurrent PCa. In this study, the diagnostic potential of 64 Cu-labeled PSMA ligand (PSMA-617) PET in patients with PCa has been investigated. The study was conducted simultaneously at two nuclear medicine centers, Austria (Vienna, Center 1) and Germany (Bad Berka, Center 2). The patients (n = 29) included in this study were referred for PET (Center 1, 21 patients) or PET/CT (Center 2, 8 patients) imaging with either a high suspicion of recurrent disease or for possible surgical or PSMA radioligand therapy planning. PET images of the whole body were performed at 1 hour p.i. and additional images of the pelvis at 2 hours p.i. In 23 of 29 patients, at least one focus of pathological tracer uptake suspicious for primary disease in the prostate lobe or recurrent disease was detected. Among healthy organs, the salivary glands, kidneys, and liver showed the highest radiotracer uptake. Lesions suspicious for PCa were detected with excellent contrast as early as 1 hour p.i. with high detection rates even at low prostate-specific antigen (PSA) levels. The preliminary results of this study demonstrate the high potential of 64 Cu-PSMA ligand PET/CT imaging in patients with recurrent disease and in the primary staging of selected patients with progressive local disease. The acquired PET images showed an excellent resolution of the detected lesions with very high lesion-to- background contrast. Furthermore, the long half-life of 64 Cu allows distribution of the tracer to clinical PET centers that lack radiochemistry facilities for the preparation of 68 Ga-PSMA ligand (satellite concept).

Diagnosis and follow-up of chronic bacterial prostatitis with recurrent urinary tract infection detected by 67Ga scintigraphy and SPECT/CT.

PubMed

Kim, Jun Ho; Baek, Ji-Hyeon; Lee, Jin Soo; Hyun, In Young

2013-11-01

Half of male populations will have symptoms and signs of prostatitis in their lifetime. There is controversy concerning diagnosis of prostatitis with (67)Ga scintigraphy because the focal midline pelvic uptake is usually considered to be physiologic uptake in colon. The authors describe (67)Ga scintigraphy and SPECT/CT findings of a 58-year-old man with right flank pain and fever. The examination demonstrated abnormal uptake of Ga within the prostate and right kidney upper pole, suggesting prostatitis and acute pyelonephritis (APN) contemporary. After completion of antibiotic treatment, follow-up scintigraphy and SPECT/CT showed complete resolution of APN, but uptake remained within the prostate.

Combination Therapy Improves Survival in Prostate Cancer Model | Center for Cancer Research

Cancer.gov

Surgery and radiotherapy are the recommended treatments for localized prostate cancer. Recurrent prostate cancer, however, is often treated with androgen-deprivation therapy. Most patients who undergo this type of therapy eventually develop castration-resistant prostate cancer (CRPC). Though initially androgen-related therapies for CRPC had been thought to be ineffective, further studies have demonstrated that the disease remains dependent on the signaling of androgens, such as testosterone, for its continued progression. This development suggests that alternative strategies for manipulating androgen signaling may prove useful for treating CRPC.

Proactive rectal warming during total-gland prostate cryoablation.

PubMed

Chen, Chung-Hsin; Pu, Yeong-Shiau

2014-06-01

Proactive rectal warming (PRW), as a modification of prostate cryoablation, was assessed in terms of rectal complications and therapeutic outcomes. A cohort of 166 patients cumulatively treated between September, 2009 and November, 2012 qualified for study, each undergoing total-gland cryoablation (TGC) for prostate cancer. The initial 100 patients accrued submitted to TGC alone. PRW was administered to the final 66 patients. Preemptive warming is achieved by inserting a cryoprobe midline through perineal skin into anterior rectal wall under ultrasound guidance. The activated probe generates warmth as the ice ball encroaches on rectum. Prospective, post-ablative grading of rectal pain was measured at weeks 1, 2, 4, 8, 12, and 24 by using the Common Terminology Criteria for Adverse Events. Recurrent prostate cancer was gauged by Phoenix criterion (nadir+2 ng/ml). The Mann-Whitney U test and Chi-square test were used to compare clinical characteristics of therapeutic subsets. The Cox proportional hazard model was applied for comparison of cancer recurrence risk by group. Rectal pain (all grades) was experienced by patients treated with (62%) and without (74%) PRW. Although such pain typically resolved with time, it was milder (general lineal model, p=0.023) and less prolonged (median: 0.75 vs 1.5 months; log-rank test, p=0.002) in patients receiving PRW than in controls. Of note, PRW did not heighten cancer recurrence risk (hazard ratio=1.3 [95% CI, 0.3-5.0]). PRW helps to protect the rectum from freeze injury during prostate cryoablation, significantly reducing post-ablative rectal pain without compromising therapeutic outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.