Lower Risk Of Biochemical Recurrence Research Articles

Prognostic Value of MRI-Assessed Central Gland Volume for Biochemical Recurrence after Prostate Cancer Radiotherapy

Introduction: Increasing central gland volume has been associated with less aggressive prostate cancer, theorized to be secondary to biomechanical stress from benign prostatic hyperplasia (BPH). The aim of this study was to evaluate pretreatment prostate magnetic resonance imaging (MRI) metrics and clinical characteristics in predicting biochemical recurrence (BCR) after definitive radiotherapy (RT) for prostate cancer. Methods: In this retrospective single institution study, we identified men in our database with prostate cancer who underwent MRI within 6 months prior to completing definitive RT from May 2011 to February 2023. Total prostate volume, central gland volume, and peripheral zone volume were measured by a radiologist using manual segmentation. The primary objective was to determine the association of central gland volume with biochemical recurrence, defined by Phoenix criteria. A multivariable Cox proportional hazards regression model was constructed and adjusted for clinical factors. Results: A total of 373 men (median age 68 years) were included, with a median follow-up of 28 months. 13 (3.5%) were low risk, 97 (26%) favorable intermediate ris, 201 (53.9%) unfavorable intermediate risk, and 62 (16.6%) high risk. 54 (14.5%) patients received conventionally fractionated RT, 105 (28.2%), moderately hypofractionated RT, 121 (32.4%), high-dose rate brachytherapy, and 93 (24.9%) stereotactic body RT. The 3 and 5 year rates of BCR were 7.8% and 18.3%, respectively. Taking into account NCCN risk group and RT type, higher central gland volume was associated with decreased risk of BCR (HR: 0.73, 95% CI: 0.55-0.98, p=0.03). No significant association was seen with peripheral zone volume, PI-RADS score, or RT type. Conclusions: Increased central gland volume on pretreatment prostate MRI is independently associated with a lower risk of biochemical recurrence after definitive radiation for prostate cancer. BPH appears to confer favorable outcomes in RT patients and represents a novel, easily quantifiable metric in risk-stratification.

Biochemical recurrence (BCR) among patients (pts) with prostate cancer (PC) after radiation therapy (RT).

e17111 Background: RT is a frequent primary treatment for pts with clinically localized PC. Despite its frequent success, 30-50% of pts eventually present with BCR, defined as rising prostate-specific antigen (PSA). BCR is associated with a higher risk of developing distant metastasis and ultimately death from PC. Understanding BCR occurrence and its impact on clinical outcomes is important for optimizing diagnostic and therapeutic strategies for recurrent disease. Methods: This is a retrospective cohort study using nationally representative Electronic Medical Records (EMR) data from Optum© from 1/2010-9/2021. Eligible pts were adults who underwent RT after PC diagnosis, had ≥ 3 available PSA values after initiating RT, and had EMR activity for at least 6 mo before and 12 mo after RT. Pts with a history of prior malignancy except nonmelanoma skin cancers and pts with metastatic PC (mPC) at baseline (BL) or within 3 months after RT were excluded. The BL period was 6 mo before RT initiation. Primary outcome was frequency of BCR, defined as rising PSA (PSA ≥ nadir + 2 ng/mL); secondary analyses included % of pts who progressed to mPC, castration-resistant PC (CRPC), and death after BCR and factors impacting time to BCR. Results: 9,292 RT pts were included in this analysis. Key pt characteristics/outcomes are shown in the Table. Median (range) age was 69.0 (40-88) y, 83.2% of pts were White, and 13.4% were Black. Median PSA nadir was 0.11 ng/mL, 32.5% of pts had received androgen deprivation therapy (ADT) during BL period, and median (Q1-Q3) follow-up from RT initiation was 3.8 (2.4-5.7) y. Overall, 10.2% of pts developed BCR. Among BCR pts (n = 949), 51.2% had a PSA doubling time (PSADT) < 6 mo and 16.9% had a PSADT between 6-10 mo; 35.0% developed mPC, 30.2% developed CRPC, and 23.4% died. In multivariate Cox regression models, the BL factor associated with the highest risk of developing BCR was PSA ≥ 20 ng/mL. Conversely, the risk of developing BCR was lower for pts who received ADT during BL. Conclusions: This real-world (RW) study evaluates BCR occurrence in pts who underwent RT with a curative intent from a large US database. The study confirms BL PSA as an important prognostic marker for BCR, while use of ADT before RT is associated with a lower risk of BCR. A considerable % of pts with BCR developed mPC (35%) or died (23%) during the study period. Novel treatment strategies are needed to delay BCR and further progression to advanced PC in pts with high-risk localized disease. [Table: see text]

MP77-15 INCREASED RISK OF BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY IN THE ACTIVE SURVEILLANCE ERA

You have accessJournal of UrologyCME1 Apr 2023MP77-15 INCREASED RISK OF BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY IN THE ACTIVE SURVEILLANCE ERA Sanjay Das, Michael Luu, Stephen Freedland, and Timothy Daskivich Sanjay DasSanjay Das More articles by this author , Michael LuuMichael Luu More articles by this author , Stephen FreedlandStephen Freedland More articles by this author , and Timothy DaskivichTimothy Daskivich More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003351.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In the active surveillance (AS) era, radical prostatectomy (RP) has become more often used for intermediate- and high-risk disease and less for low-risk disease. AS/conservative management became the most common treatment for low-risk disease in the VA in 2010. However, the impact of this shift on risk of biochemical recurrence (BCR) after RP is unknown. We sought to determine how risk of BCR has changed before and after 2010 and to provide contemporary projections for BCR by tumor risk. METHODS: We sampled men who underwent RP for clinically localized disease between 2000 and 2017 from the VA SEARCH database. Kaplan Meier analysis was used to calculate incidence of BCR before and after 2010 overall and across tumor risk subgroups. Multivariable Cox proportional hazard regression analysis including an interaction term between epoch and tumor risk was used to compare risk of BCR before and after 2010 overall and across tumor risk subgroups. RESULTS: Of 5,648 patients, 3,276 (58%) underwent RP in 2010 or prior and 2,372 (42%) after 2010. Of those who underwent RP in 2010 or prior, 1,266 (39%), 503 (15%), 655 (20%), and 712 (22%) had low-, favorable intermediate-, unfavorable intermediate-, and high-risk disease, respectively, compared with 335 (14%), 488 (21%), 768 (32%), and 749 (32%) among those who underwent RP after 2010 (p<0.001). The 7-year risk of BCR in the post-2010 was 43%, compared with 33% in the pre-2010 era (HR 1.15, 95%CI 1.04–1.28). In a multivariable Cox model adjusting for tumor risk, there was a significant interaction between tumor risk and epoch in predicting BCR (p<0.001). Men with favorable intermediate risk (HR 0.71, 95%CI 0.53–0.96) and unfavorable intermediate risk disease (HR 0.74, 95%CI 0.61–0.90) had a lower risk of BCR in the post-2010 era. Men with high-risk disease (HR 1.24, 95%CI 1.06–1.45) had higher risk of BCR in the post-2010 (vs. pre-2010) era. The 5-year risk of BCR in the pre- vs. post-2010 eras were 17% vs. 15%, 23% vs. 20%, 40% vs. 33%, and 46% vs. 52% for low, favorable intermediate, unfavorable intermediate, and high-risk disease, respectively. CONCLUSIONS: Trends toward using RP for higher risk disease have increased the 7-year risk of BCR from 33% to 43% in the pre- vs. post-AS eras, primarily driven by increased risk of BCR in high-risk patients. Source of Funding: This research was supported by Cedars-Sinai Cancer at Cedars-Sinai Medical Center through the Biostatistics Core Voucher Program. Dr. Das was supported by the Patient Centered Outcomes in Urologic and Gynecologic Cancers (PCORT: UroGynCan) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1108 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sanjay Das More articles by this author Michael Luu More articles by this author Stephen Freedland More articles by this author Timothy Daskivich More articles by this author Expand All Advertisement PDF downloadLoading ...

Identifying Patients in Whom the Follow-Up Scheme after Robot-Assisted Radical Prostatectomy Could Be Optimized in the First Year after Surgery: Reducing Healthcare Burden.

The currently advised follow-up scheme of PSA testing after robot-assisted radical prostatectomy (RARP) is strict and might pose a burden to our healthcare system. We aimed to optimize the 1-year follow-up scheme for patients who undergo RARP. All patients with histologically-proven prostate cancer (PCa) who underwent RARP between 2018 and August 2022 in the Prostate Cancer Network in the Netherlands were retrospectively evaluated. We excluded patients who underwent salvage RARP and patients who had <1 year of PSA follow-up. Postoperative PSA values were collected. Biochemical persistence (BCP) was defined as PSA level >0.10 ng/mL at 0-4 months after RARP, whereas biochemical recurrence (BCR) was defined as PSA level >0.2 ng/mL at any time point after RARP. We aimed to identify a group of patients who had a very low risk of BCR at different time points after surgery. Of all 1155 patients, BCP was observed in 151 (13%), of whom 79 (6.8%) had PSA ≥ 0.2 ng/mL. BCR further developed in 51 (4.7%) and 37 (3.4%) patients at 5-8 and 9-12 months after RARP, respectively. In 12 patients, BCR was found at 5-8 months after RARP in the absence of BCP. These patients represented 1.2% (12/1004) of the entire group. In other words, 98.8% (992/1004) of patients who had an unmeasurable PSA level at 0-4 months after RARP also had an unmeasurable PSA level 5-8 months after surgery. Limitations are the retrospective design and incomplete follow-up. Patients with an unmeasurable PSA level at 3-4 months after RARP may not need to be retested until 12 months of follow-up, as almost 100% of patients will not have the biochemically recurrent disease at 5-8 months of follow-up. This will reduce PSA testing substantially at the cost of hardly any missed patients with recurrent disease.

Salvage Radical Prostatectomy for Recurrent Prostate Cancer Following First-line Nonsurgical Treatment: Validation of the European Association of Urology Criteria in a Large, Multicenter, Contemporary Cohort

Salvage radical prostatectomy (sRP) is a potentially curative option for locally radiorecurrent prostate cancer (PCa) but is associated with significant morbidity. Therefore, the European Association of Urology (EAU) guidelines recommend restricting sRP to a favorable-prognosis group according to the EAU criteria, but these have been validated considering only biochemical recurrence (BCR). Our aim was to test these criteria in a large, multicenter, contemporary cohort. We retrospectively reviewed 1265 patients who underwent sRP at 14 referral centers (2000–2021), stratified by compliance with the EAU criteria. Our primary outcome was metastasis-free survival (MFS). We included 1030 men, of whom 221 (21.5%) fully met the EAU recommended criteria for sRP and 809 (78.5%) did not. The EAU-compliant group experienced more favorable pathological and functional outcomes (79% vs 63% wearing no pads at 1 yr; p < 0.001) and had significantly better MFS (90% vs 76% at 5 yr; p < 0.001), prostate-specific antigen–free survival (55% vs 38% at 5 yr; p < 0.001), and overall survival (89% vs 84% at 5 yr; p = 0.01). This was verified by Cox regression analysis for MFS (hazard ratio 1.84, 95% confidence interval 1.13–2.99; p = 0.01). We found that adherence to the EAU criteria is associated with a lower risk of BCR and, more importantly, of metastasis after surgery. Patient summaryWe looked at outcomes of surgical removal of the prostate for prostate cancer recurrence after radiotherapy or other nonsurgical treatments according to whether or not patients met the European Association of Urology (EAU) criteria for this surgery. We found that men who did not meet the criteria had a higher risk of metastasis and their benefit from surgery might be significantly less than for patients who do meet the EUA criteria.

MP51-16 THE RISK OF RECURRENCE IN CN1 PROSTATE CANCER PATIENTS TREATED WITH RADICAL PROSTATECTOMY VARIES ACCORDING TO THE TYPE PREOPERATIVE STAGING. A COMPARISON BETWEEN 68GA-PSMA-PET VERSUS CONVENTIONAL IMAGING IN A LARGE, MULTI-INSTITUTIONAL STUDY

MP51-16 THE RISK OF RECURRENCE IN CN1 PROSTATE CANCER PATIENTS TREATED WITH RADICAL PROSTATECTOMY VARIES ACCORDING TO THE TYPE PREOPERATIVE STAGING. A COMPARISON BETWEEN 68GA-PSMA-PET VERSUS CONVENTIONAL IMAGING IN A LARGE, MULTI-INSTITUTIONAL STUDY

Cost-effectiveness of Robotic-Assisted Radical Prostatectomy for Localized Prostate Cancer in the UK

The cost-effectiveness of different surgical techniques for radical prostatectomy remains a subject of debate. Emergence of recent critical clinical data and changes in surgical equipment costs due to their shared use by different clinical specialties necessitate an updated cost-effectiveness analysis in a centralized, largely government-funded health care system such as the UK National Health Service (NHS). To compare robotic-assisted radical prostatectomy (RARP) with open radical prostatectomy (ORP) and laparoscopic-assisted radical prostatectomy (LRP) using contemporary data on clinical outcomes, costs, and surgical volumes in the UK. This economic analysis used a Markov model developed to compare the cost-effectiveness of RARP, LRP, and ORP to treat localized prostate cancer. The model was constructed from the perspective of the UK NHS. The model simulated 65-year-old men who underwent radical prostatectomy for localized prostate cancer and were followed up for a 10-year period. Data were analyzed from May 1, 2020, to July 31, 2021. Robotic-assisted radical prostatectomy, LRP, and ORP. Quality-adjusted life-years (QALYs), costs (direct medical costs and costs outside the NHS), and incremental cost-effectiveness ratios (ICERs). Compared with LRP, RARP cost £1785 (US $2350) less and had 0.24 more QALYs gained; thus, RARP was a dominant option compared with LRP. Compared with ORP, RARP had 0.12 more QALYs gained but cost £526 (US $693) more during the 10-year time frame, resulting in an ICER of £4293 (US $5653)/QALY. Because the ICER was below the £30 000 (US $39 503) willingness-to-pay threshold, RARP was more cost-effective than ORP in the UK. The most sensitive variable influencing the cost-effectiveness of RARP was the lower risk of biochemical recurrence (BCR). Scenario analysis indicated RARP would remain more cost-effective than ORP as long as the BCR hazard ratios comparing RARP vs ORP were less than 0.99. These findings suggest that in the UK, RARP has an ICER lower than the willingness-to-pay threshold and thus is likely a cost-effective surgical treatment option for patients with localized prostate cancer compared with ORP and LRP. The results were mainly driven by the lower risk of BCR for RARP. These findings may differ in other health care settings where different thresholds and costs may apply.

The association of phosphodiesterase-5 inhibitors with the biochemical recurrence-free and overall survival of patients with prostate cancer following radical prostatectomy

To determine whether phosphodiesterase-5 inhibitor documentation is associated with biochemical relapse-free and overall survival of patients with prostate cancer treated with radical prostatectomy.We undertook a retrospective cohort analysis of 3,100 patients with prostate cancer treated with radical prostatectomy between 2003 and 2015. The patients were categorized as a phosphodiesterase- 5- inhibitor user or non-user. The biochemical relapse-free and overall survival at 5-years and 10-years were determined.Of the patients, 1,372 reported phosphodiesterase-5 inhibitor documentation, and 1,728 did not. The biochemical recurrence-free survival for non-users at 5- and 10-years follow-up was 87.6% and 85.3%, respectively, and the overall survival at these time intervals was 97.9% and 94.5%. The biochemical recurrence-free survival for phosphodiesterase-5 inhibitor users was 94.3% and 93.2% at 5- and 10-years follow-up, respectively, and overall survival was 99.2% and 95.8% at these intervals. The hazard ratio for biochemical recurrence-free survival was 0.44 (CI 0.34-0.56) and for overall survival was 0.65 (CI 0.45-0.94). On the multivariate analysis, phosphodiesterase-5 inhibitor documentation was associated with a lower risk of biochemical recurrence and death when corrected for the other variables. Age at surgery and Gleason scores >8 was associated with a higher risk of death. Higher pathological stage, higher Gleason score, presence of lymph node metastases, and nonwhite race were associated with a higher risk of recurrence.This retrospective analysis revealed a significant association of postoperative phosphodiesterase-5 inhibitor documentation with biochemical recurrence-free- and overall survival in patients with localized prostate cancer treated with radical prostatectomy. Larger scale studies are warranted to investigate the clinical significance of this association.

A novel imaging based Nomogram for predicting post-surgical biochemical recurrence and adverse pathology of prostate cancer from pre-operative bi-parametric MRI.

BackgroundWe developed and validated an integrated radiomic-clinicopathologic nomogram (RadClip) for post-surgical biochemical recurrence free survival (bRFS) and adverse pathology (AP) prediction in men with prostate cancer (PCa). RadClip was further compared against extant prognostics tools like CAPRA and Decipher.MethodsA retrospective study of 198 patients with PCa from four institutions who underwent pre-operative 3 Tesla MRI followed by radical prostatectomy, between 2009 and 2017 with a median 35-month follow-up was performed. Radiomic features were extracted from prostate cancer regions on bi-parametric magnetic resonance imaging (bpMRI). Cox Proportional-Hazards (CPH) model warped with minimum redundancy maximum relevance (MRMR) feature selection was employed to select bpMRI radiomic features for bRFS prediction in the training set (D1, N = 71). In addition, a bpMRI radiomic risk score (RadS) and associated nomogram, RadClip, were constructed in D1 and then compared against the Decipher, pre-operative (CAPRA), and post-operative (CAPRA-S) nomograms for bRFS and AP prediction in the testing set (D2, N = 127).Findings“RadClip yielded a higher C-index (0.77, 95% CI 0.65-0.88) compared to CAPRA (0.68, 95% CI 0.57-0.8) and Decipher (0.51, 95% CI 0.33-0.69) and was found to be comparable to CAPRA-S (0.75, 95% CI 0.65-0.85). RadClip resulted in a higher AUC (0.71, 95% CI 0.62-0.81) for predicting AP compared to Decipher (0.66, 95% CI 0.56-0.77) and CAPRA (0.69, 95% CI 0.59-0.79).”InterpretationRadClip was more prognostic of bRFS and AP compared to Decipher and CAPRA. It could help pre-operatively identify PCa patients at low risk of biochemical recurrence and AP and who therefore might defer additional therapy.FundingThe National Institutes of Health, the U.S. Department of Veterans Affairs, and the Department of Defense.

Clinical Outcomes of Combined Prostate- and Metastasis-Directed Radiation Therapy for the Treatment of De Novo Oligometastatic Prostate Cancer

PurposeThe Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trial reported overall survival benefits for prostate-directed radiation therapy (PDRT) in low-burden metastatic prostate cancer. Oligometastasis-directed radiation therapy (ORT) improves androgen deprivation therapy (ADT)–free and progression-free survivals. Comprehensive PDRT + ORT to all detectable metastases may offer benefit for de novo oligometastatic prostate cancer (DNOPC) and is under prospective study; given few available benchmarks, we reviewed our institutional experience. Methods and MaterialsForty-seven patients with DNOPC with predominantly M1b disease received neoadjuvant, concurrent, and adjuvant ADT plus PDRT + ORT to 1 to 6 oligometastases. Gross pelvic (N1) nodes were not considered oligometastases unless focally targeted without broader nodal coverage. Outcomes were analyzed from radiation therapy (RT) start using Kaplan-Meier, competing risks, and Cox regression. Median follow-up was 27 (95% confidence interval, 16-42) months. ResultsAt 1- and 2-years post-RT, cumulative incidence of distant metastatic progression (DMP) was 21% and 32%, whereas overall survival was 90% and 87%, respectively. Neuroendocrine/intraductal histology, prostate-specific antigen (PSA) < 20, and detectable PSA after PDRT + ORT were associated with increased DMP risk; number and location of oligometastases were not. Local failure was rare, with 3 prostate recurrences and progression of 10 treated oligometastases during follow-up. After neoadjuvant ADT, 9 (19%) patients had undetectable PSA (<0.05 ng/mL), which increased to 32 (68%) after PDRT + ORT. Overall 2-year incidence of biochemical recurrence (BCR) and development of castrate resistance were 23% and 36%, respectively. Undetectable PSA post-RT was associated with lower risk of BCR (hazard ratio, 0.19; P = .004) and DMP (hazard ratio, 0.26; P = .025). Overall, 23 (49%) patients were trialed off ADT; 16 (70%) had testosterone recovery (>150 ng/dL) and, of these, 5 had subsequent PSA rise and restarted ADT 2 to 21 months postrecovery. The remaining 11 were maintained off ADT without BCR. Median noncastrate duration was 8 months; 7 patients had normalized testosterone for >1 year. ConclusionsA comprehensive, radiotherapeutic-based treatment strategy has favorable clinical outcomes and can produce prolonged noncastrate remissions in a subset with DNOPC.

Specific spatial distribution patterns of tumor foci are associated with a low risk of biochemical recurrence in pT2pN0R0 prostate cancer.

The previous attempts for pT2 substaging of prostate cancer (PCa) were insufficient in providing prognostic subgroups and the search for new prognostic parameters to subcategorize pT2 PCa is, therefore, needed. Therefore, the current study investigated the association between tumor distribution patterns and the biochemical recurrence (BCR)-free survival rate in pT2pN0R0 PCa. Following radical prostatectomy, the anatomical distribution of PCa in 743 men with pT1-pT3pN0 disease was analyzed to determine 20 types of PCa distribution patterns. Then, 245 men with pT2pN0R0 PCa was considered for prognostic evaluation with a mean follow-up period of 60months. The spatial distribution patterns of PCa were evaluated using a cMDX©-based map model of the prostate. An analysis including 552,049 comparison operations was performed to assist in the evaluation of the similarity levels of the distribution patterns. A k-mean cluster analysis was applied to determine groups with similar distribution patterns. A decision-tree analysis was performed to divide these groups according to frequency of BCR. The BCR-free survival rate was analyzed using Kaplan-Meier curves. Predictors of progression were investigated using a Cox proportional hazards model. BCR occurred in 8.2% of the 245 men with pT2pN0R0 PCa. The median time of recurrence was 60months (interquartile range [IQR]: 42-77). In univariate and multivariate analyses, the prostate volume and the distribution patterns were independent predictors for BCR, whereas the sub-staging of pT2 tumors, Gleason grading, prostate-specific antigen (PSA) level, and relative tumor volume were not. In the patients with pT2pN0R0 disease, PCa distribution patterns with the apical involvement were significantly associated with the risk of BCR (P = 0.001). The spread tumor patterns with the apical involvement are associated with a high-risk of BCR in the pT2 tumor stage. The vertical tumor spread could be considered in developing improved prognostic pT2 sub-categories.

Abstract C028: Hypoxia-associated genes on disparities in the aggressiveness of prostate cancer

Abstract The incidence of prostate cancer (PCa) is 70% greater and the mortality rate 137% higher in African-American men (AAM) relative to Caucasian-American men (CAM) (Siegel et al., 2016). AAM also show faster tumor growth, higher levels of PSA, and more aggressive disease relative to CAM (Martin et al., 2013). These data, related to the biology of PCa, suggest that biologic mechanisms contribute to PCa health disparities. Because stratification by clinical parameters alone is not sufficient to predict aggressive PCa, there is an unmet need of reliable biomarkers to anticipate outcome and disease progression. This study was designed to identify hypoxia-associated genes with the potential to anticipate the risk of aggressive PCa in a race-specific manner. Seventy annotated cases with documented follow-up for evidence of biochemical recurrence (BCR) were located. Of these, 22 were AAM (8 with BCR and 14 without BCR) and 48 were CAM (31 with BCR and 17 without BCR). Next, we performed a global sequencing analysis in RNA extracted from formalin-fixed, paraffin-embedded blocks. Among 27 hypoxia-associated genes associated with race and PCa by use of Cox proportional hazards regression analysis (p ≤ 0.05), we identified three genes related with BCR and race: regulator of G-protein signaling 1 (RGS1), nuclear receptor subfamily 3, group C, member 1-glucocorticoid receptor (NR3C1), and myosin light chain kinase (MYLK). A race-independent in silico analysis utilizing TCGA data suggested tumor-specific association between transcripts of RGS1, NR3C1, and MYLK and Gleason score. Likewise, low expression of these transcripts was suggestive of poor survival. Currently, we are analyzing transcripts of these three hypoxia-associated genes by independent techniques. Integration of gene expression data with clinical parameters of prognosis will allow us to develop predictive scores. These studies may enable race-specific differentiation of patients at higher and lower risk of BCR. Our findings underscore the prognostic value of hypoxia-regulated genes in aggressive PCa. They also warrant studies to establish the relevance of RGS1, NR3C1, and MYLK as race-specific markers. Funding sources: GMaP 2 Pilot Grant (IE). Citation Format: Ingrid C. Espinoza, Carlos S. Moreno, Christian R. Gomez. Hypoxia-associated genes on disparities in the aggressiveness of prostate cancer [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C028.

PD63-09 ONCOLOGICAL OUTCOME OF LOCALIZED, LYMPH NODE-POSITIVE PROSTATE CARCINOMA AFTER RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy V (PD63)1 Apr 2020PD63-09 ONCOLOGICAL OUTCOME OF LOCALIZED, LYMPH NODE-POSITIVE PROSTATE CARCINOMA AFTER RADICAL PROSTATECTOMY Lara Franziska Stolzenbach*, Philipp Mandel, Florian Loecherbach, Uwe Michl, Hans Heinzer, Markus Graefen, and Thomas Steuber Lara Franziska Stolzenbach*Lara Franziska Stolzenbach* More articles by this author , Philipp MandelPhilipp Mandel More articles by this author , Florian LoecherbachFlorian Loecherbach More articles by this author , Uwe MichlUwe Michl More articles by this author , Hans HeinzerHans Heinzer More articles by this author , Markus GraefenMarkus Graefen More articles by this author , and Thomas SteuberThomas Steuber More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000980.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Pathologically confirmed regional lymph node metastases represent a major prognostic factor in patients with prostate cancer (PCa) who undergo radical prostatectomy (RP). Rarely, positive lymph nodes (pN1) are also observed in localized (pT2) PCa after RP. The aim of this study was to investigate the oncological outcomes after RP in patients with pT2 pN1 cM0 PCa. METHODS: Within a single institution database (1992-2018), we retrospectively analyzed 28,647 PCa patients who underwent radical prostatectomy between 1992 and 2018. Kaplan-Meier plots were used to depict biochemical recurrence (BCR)-free survival and multivariable Cox regression models were used to test for predictors of BCR, within patients who harboured pT2 N1 M0 PCa. RESULTS: Of 28,647 patients, 241 (0.8%) harboured pT2 N1 M0 PCa at the final pathological evaluation. This represents 1.3% of all pT2 PCa patients (n=18,369) and 8.9% of all pN1 (n=2,701) patients. Within the pT2 N1 M0 patients, the number of positive lymph nodes revealed as following: 175 (72.6%) patients had 1 positive lymph node, 41 (17.0%) patients had 2 positive lymph nodes, 25 (10.4%) patients had ³3 positive lymph nodes. The median follow-up of all patients was 36.3 months. 20 (8.3%) and 56 (23.2%) pT2 N1 M0 PCa patients received either adjuvant (aRT) or salvage radiation (sRT), respectively. 3 and 16 patients received additionally to the RT adjuvant antiandrogen therapy (ADT) or salvage ADT. 3 (1.2%) and 15 (6.2%) pT2 N1 M0 PCa patients were only treated with either adjuvant or salvage ADT. During the follow-up, 4 (1.6%) individuals died of PCA and 16 developed metastases, which resulted in a 5-year MFS of 92.5%. Median BCR-free survival was 36.3 months and 5-year BCR-free survival rate was of 54.7 %, within the entire pT2 N1 M0 PCa cohort. Of these, patients who received only aRT showed significantly higher BCR-free rates compared to patients who did not received any treatment (5-year BCR free survival: 94.1% vs. 80.5%; p=0.001). In the multivariable analyses adjusted for preoperative PSA value, two or more positive lymph nodes (HR 1.97, p=0.02 for 2 vs.1 and HR 4.41, p<0.01 for >=3 vs. 1), and Gleason grading group IV-V (HR 2.04, p=0.03) were associated with a higher risk of BCR. Conversely, use of aRT (HR 0.27, p=0.04) was associated with a lower risk of BCR. CONCLUSIONS: Pathologically confirmed positive lymph node disease is a rare finding within patients with pT2 PCa. 5-year BCR-free survival was 54.7% in pT2 pN1 patients. However, two or more positive lymph nodes, a Gleason grade group IV-V represent risk factors for BCR. In consequence, adjuvant radiotherapy should be recommended in patients with these clinical-pathological characteristics. Source of Funding: There was no external financial support for this study. The authors declare that they have no conflict of interest. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1296-e1296 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lara Franziska Stolzenbach* More articles by this author Philipp Mandel More articles by this author Florian Loecherbach More articles by this author Uwe Michl More articles by this author Hans Heinzer More articles by this author Markus Graefen More articles by this author Thomas Steuber More articles by this author Expand All Advertisement PDF downloadLoading ...

Selection of patients who would not require long-term prostate-specific antigen monitoring after low-dose-rate brachytherapy

PurposeTo identify patients at extremely low risk of biochemical recurrence (BCR) of prostate cancer after low-dose-rate brachytherapy (LDR-BT) to determine when prostate-specific antigen (PSA) monitoring can be stopped. Methods and MaterialsWe retrospectively reviewed clinicopathologic data of patients with prostate cancer who underwent LDR-BT between 2003 and 2011. Of 1569 patients reviewed, 689 (43.9%) received combination external beam radiotherapy, and 970 (61.8%) had neoadjuvant hormonal therapy. We stratified patients according to risk factors identified by multivariate analysis and assessed the factors for an association with BCR (defined as ≥2 ng/mL higher than the nadir). ResultsThe median followup was 96 months. Of 1531 patients who were BCR-free at 3 years after treatment, 76 subsequently developed BCR; of 1500 who were BCR-free at 5 years, 45 eventually had BCR. On multivariate analysis, independent risk factors for BCR were the National Comprehensive Cancer Network risk group at diagnosis and PSA levels at 3 or 5 years after radiotherapy. In the low-risk group, no patient with a PSA level ≤0.2 ng/mL at 3 years after radiotherapy subsequently developed BCR. In the intermediate-risk group, no patients with a PSA level ≤0.2 ng/mL at 5 years subsequently developed BCR. ConclusionsThe National Comprehensive Cancer Network risk group at diagnosis and PSA values at 3 and 5 years after LDR-BT are independently associated with a risk of later BCR. Using these two factors may help to select patients for whom PSA monitoring could be stopped because they have an extremely low risk of later BCR.

Lymph node yield during radical prostatectomy does not impact rate of biochemical recurrence in patients with seminal vesicle invasion and node-negative disease

ObjectivesSeminal 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. MethodsA 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. ResultsMedian 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). ConclusionSeminal 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.

Positive margin length and highest Gleason grade of tumor at the margin predict for biochemical recurrence after radical prostatectomy in patients with organ-confined prostate cancer.

To evaluate the pathologic features after radical prostatectomy to determine if the length of positive surgical margin (PSM) and the highest Gleason grade within the tumor at the PSM could risk stratify patients for biochemical recurrence (BCR). We performed a retrospective, matched, cohort study to identify patients with pathologically organ-confined (pT2) tumors and negative nodes (pN0/Nx), receiving no adjuvant therapy. Specimens underwent single pathologist review. BCR-free survival was estimated using the Kaplan-Meier method and compared between subgroups using two-sided log-rank test. Using Classification and Regression Tree analysis (CART), we identified an optimal cutoff for the PSM length which differentiated risk for BCR. Cox proportional hazards regression models were fit to assess the association between variables and BCR-free survival. Two-hundred PSM patients were matched to 200 patients with negative surgical margins (NSM). Median follow-up was 64 months. 5 year BCR-free survival was 90% (95% CI 84-97%) in the NSM group and 70% (95% CI 63-79%) in the PSM group. There was an increased risk of BCR with any PSM. Multivariable analysis demonstrated an association with length of PSM ( > 1 mm vs. ≤ 1 mm, HR 2.29; 95% CI 1.2-4.5) and having a highest Gleason grade of the cancer focus at the margin ≥ 4 (HR 6.8; 95% CI 1.6-29). We demonstrated that patients with pathologic T2 tumors with PSM > 1 mm or a Gleason grade of tumor focus at the margin ≥ 4 are at elevated risk for BCR. However, this study suggests that patients with pT2 tumors with positive surgical margins have a relatively low risk of biochemical recurrence and adjuvant radiation may be over treating this sub population. The subsets at greatest risk for BCR may benefit from more frequent PSA monitoring to direct salvage therapies.

MP97-08 PREDICTION OF EXTREME UPGRADE FROM BIOPSY GRADE 1 TO GRADE 4 OR 5 AT RADICAL PROSTATECTOMY: THE IMPORTANCE OF THE EXTENT OF BIOPSY SAMPLING

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy VIII1 Apr 2017MP97-08 PREDICTION OF EXTREME UPGRADE FROM BIOPSY GRADE 1 TO GRADE 4 OR 5 AT RADICAL PROSTATECTOMY: THE IMPORTANCE OF THE EXTENT OF BIOPSY SAMPLING Emanuele Zaffuto, Giorgio Gandaglia, Marco Bandini, Paolo Dell'Oglio, Nicola Fossati, Francesco Pellegrino, Vincenzo Mirone, Vito Cucchiara, Marco Bianchi, Federico Dehó, Emanuele Montanari, Nazareno Suardi, Rodolfo Montironi, Francesco Montorsi, and Alberto Briganti Emanuele ZaffutoEmanuele Zaffuto More articles by this author , Giorgio GandagliaGiorgio Gandaglia More articles by this author , Marco BandiniMarco Bandini More articles by this author , Paolo Dell'OglioPaolo Dell'Oglio More articles by this author , Nicola FossatiNicola Fossati More articles by this author , Francesco PellegrinoFrancesco Pellegrino More articles by this author , Vincenzo MironeVincenzo Mirone More articles by this author , Vito CucchiaraVito Cucchiara More articles by this author , Marco BianchiMarco Bianchi More articles by this author , Federico DehóFederico Dehó More articles by this author , Emanuele MontanariEmanuele Montanari More articles by this author , Nazareno SuardiNazareno Suardi More articles by this author , Rodolfo MontironiRodolfo Montironi More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , and Alberto BrigantiAlberto Briganti More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.3052AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Gleason grading is an important predictor of oncologic outcomes in prostate cancer (PCa) patients. However, some patients with biopsy grade 1 disease might experience extreme upgrading to grade group 4-5 at radical prostatectomy (RP). We identified predictors of extreme upgrading in men treated at a single referral center METHODS We identified 1,718 patients diagnosed with biopsy grade group 1 PCa, clinical stage T1/T2, at a single center between 1991 and 2015 and treated with RP. Extreme upgrading was defined as switching to grade 4 or 5 at final pathology. Patients were stratified according to presence of extreme upgrading. Uni- and multivariable logistic regression analyses (MVA) assessed the relationship between clinical and preoperative characteristics and the risk of extreme upgrading. Finally, 146 individuals diagnosed with biopsy grade 4-5 PCa and clinical T1 or T2 disease were abstracted from the database and compared with patients who experienced extreme upgrading at RP. Cox regression analyses evaluated differences in biochemical recurrence (BCR) rates according to grade group 1 vs. grade 4-5 PCa at biopsy after adjusting for confounders RESULTS 46 individuals (2.7%) were diagnosed with grade 4-5 PCa after RP. These patients were older compared to those who did not experience extreme upgrading (p<0.01) and had a significantly higher PSA at diagnosis (7.6 vs. 6.2 mg/dL; p=0.03). A lower number of cores were taken during biopsy for patients who experienced extreme upgrading at RP (12 vs 14; p<0.01). At MVA, age (OR: 1.05; p=0.03), PSA (OR: 1.04; p<0.001) and the number of cores taken (OR: 0.92; p=0.01) were independent predictors of extreme upgrading. The MVA model was used to plot predicted probability of extreme upgrading at RP according to the number of cores taken (Fig. 1). When comparing patients who experienced extreme upgrading with 146 individuals diagnosed with biopsy grade 4-5 PCa, those diagnosed with biopsy grade 1 were at lower risk of BCR (HR: 0.52; p=0.02) CONCLUSIONS An adequate biopsy sampling reduces the risk of underestimation of high-risk PCa. Patients with grade 1 PCa experience better outcomes compared to those diagnosed with more aggressive disease at biopsy. These considerations are of pivotal importance for more accurate risk stratification © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1306 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Emanuele Zaffuto More articles by this author Giorgio Gandaglia More articles by this author Marco Bandini More articles by this author Paolo Dell'Oglio More articles by this author Nicola Fossati More articles by this author Francesco Pellegrino More articles by this author Vincenzo Mirone More articles by this author Vito Cucchiara More articles by this author Marco Bianchi More articles by this author Federico Dehó More articles by this author Emanuele Montanari More articles by this author Nazareno Suardi More articles by this author Rodolfo Montironi More articles by this author Francesco Montorsi More articles by this author Alberto Briganti More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Phosphodiesterase type 5 inhibitors (PDE5i) and prostate cancer recurrence.

55 Background: Phosphodiesterase type 5 inhibitors are commonly used for management of erectile dysfunction after prostate cancer (CaP) treatment. Single-institution studies have reported conflicting data on PDE5i use and recurrence after radical prostatectomy (RP). We re-evaluated the association between PDE5i use after RP and RT with biochemical recurrence in a nationwide, population-based registry. Methods: We performed a nested case-control study using data from the National Prostate Cancer Register of Sweden (including &gt;98% prostate cancer cases nationwide), linked to the national Prescribed Drug Register. Among men with localized CaP who underwent primary RT or RP from 2006-2007 with 5 years of follow-up, we identified those with biochemical recurrence (n=293 cases). For each case, we identified 20 controls who were recurrence-free at the event date of the index case, using incidence density sampling stratified by age and treatment (n=5,767 controls). Multivariable conditional logistic regression was used to examine the relationship between overall PDE5i use and cumulative pill number with biochemical recurrence. Results: Among men treated by RT, PDE5i were not associated with BCR (OR 0.97, 95% CI 0.48-1.94), adjusting for marital status, education, income, PSA, clinical stage, Gleason score, and proportion of positive biopsies. As shown in the table, PDE5i were not associated with biochemical recurrence after RP adjusting for clinical features (OR 0.79, 95% CI 0.60-1.05), or with additional adjustment for surgical pathology (OR 0.83, 95% CI 0.62-1.10). Men whose cumulative number of PDE5i pills was above the median had a slightly lower risk of biochemical recurrence in the clinical model, and no difference in risk of biochemical recurrence after adjustment for RP features. Conclusions: Our results from a population-based setting suggest against an increased risk of biochemical recurrence among men using PDE5i after CaP treatment. [Table: see text]

Preoperative prostate health index is an independent predictor of early biochemical recurrence after radical prostatectomy: Results from a prospective single-center study

BackgroundThe aim of this study was to test the hypothesis that preoperative prostate health index (PHI) levels could help to predict early biochemical recurrence (BCR) in a contemporary population of patients with prostate cancer treated with robot-assisted radical prostatectomy (RARP). MethodsThe study population consisted of 313 patients treated with RARP for clinically localized prostate cancer at a single institution between 2010 and 2011. Patients subjected to neoadjuvant or adjuvant therapies and patients with a follow-up of<2 years were excluded. BCR was defined as a postoperative level of total prostate-specific antigen≥0.2ng/ml and elevating after RARP. The minimum P-value method was used to determine the most significant PHI cutoff value to discriminate between patients with and without BCR. The Kaplan-Meier method was used to determine BCR-free survival rates. Finally, Cox regression models were fitted to determine the predictors of BCR, and the predictive accuracy (area under the curve) of each predictor was determined with the Harrell concordance index. ResultsMean total prostate-specific antigen and mean PHI levels were 5.76ng/ml (interquartile range: 4.2–8.7) and 46.0 (35–62), respectively. Biopsy Gleason score was 6 in 173 (55.3%), 7 in 121 (38.7%), and≥8 in 19 (6.1%) patients. At final pathology, extracapsular extension was observed in 59 (18.8%), seminal vesicle invasion in 24 (7.7%), and lymph node invasion in 11 (3.5%) patients, whereas 228 (72.8%) patients had organ-confined disease. The 2-year BCR-free survival rate was 92.5% in the overall population and was 96.7% in patients with organ-confined disease. The most significant PHI cutoff value to discriminate between patients with and without BCR was 82. Specifically, the 2-year BCR-free survival rate was 97.7% in patients with a preoperative PHI level<82 relative to 69.7% in patients with a PHI level≥82 (log-rank test: P<0.001). Finally, in multivariable Cox regression analyses, PHI level emerged as an independent predictor of BCR in both the preoperative and the postoperative settings and was more accurate than several established BCR predictors were. ConclusionsPreoperative PHI levels may discriminate between patients who are at a high risk vs. low risk of BCR after RARP. External validation of our findings within a larger population with a longer follow-up time is needed.

Elevated serum microRNA levels associate with absence of high-grade prostate cancer in a retrospective cohort.

To reduce treatment of indolent prostate cancer (PCa), biomarkers are needed to improve identification of patients with a low-risk of having aggressive disease. Over-treatment of these patients occurs because of uncertainty in the aggressiveness of the entire tumor based on the biopsies, which do not accurately sample multifocal tumors. Circulating microRNAs (miRNAs) are stable serum markers and differential miRNA levels occur in men with PCa. The goal of this study was to identify circulating miRNAs that were associated with aggressive or indolent PCa. We measured circulating miRNAs in 150 patients prior to surgery and compared the miRNA levels to the pathology of the entire radical prostatectomy specimen. For this study we used an exceptionally well-characterized cohort of patients who had benign prostatic hyperplasia (BPH), low-grade or high-grade PCa. Low-grade was defined as patients with 100% Gleason grade 3 tumor as determined by step-wise sectioning. High-grade PCa patients had 30-90% Gleason grade 4+5 in the tumor. BPH patients had at least two biopsies negative for PCa. Twenty one miRNAs were selected for analysis. The miRNAs were quantified by RT-qPCR and analyzed by logistic regression. High levels of 14 miRNAs were exclusively present in the serum from patients with low-grade PCa or BPH, compared to men with high-grade PCa who had consistently low levels. The expression levels of the 14 miRNAs were combined into a “miR Score” which had a negative predictive value (NPV) of 0.939 to predict absence of high-grade PCa among PCa and BPH patients. Biochemical recurrence (BCR) was known for the PCa patients and a combined “miR Risk Score” accurately classified a subset of patients with low risk of BCR (NPV 0.941). In summary, measurement of serum miRNAs may have pre-surgical utility in combination with clinical risk calculators to identify patients with low risk of harboring aggressive PCa.