Favorable Intermediate Risk Research Articles

PD20-05 RISK OF MEN WITH INTERMEDIATE RISK PROSTATE CANCER GOING ONTO DEFINITIVE TREATMENT DURING ACTIVE SURVEILLANCE; DOES A HIGH PSA PREDICT A WORSE OUTCOME?

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance III1 Apr 2018PD20-05 RISK OF MEN WITH INTERMEDIATE RISK PROSTATE CANCER GOING ONTO DEFINITIVE TREATMENT DURING ACTIVE SURVEILLANCE; DOES A HIGH PSA PREDICT A WORSE OUTCOME? John Burns, Lauren Hurwitz, Katherine Levie, Fernando Caumont, Timothy Brand, Inger Rosner, Sean Stroup, Joseph Sterbis, Jennifer Cullen, and Christopher Porter John BurnsJohn Burns More articles by this author , Lauren HurwitzLauren Hurwitz More articles by this author , Katherine LevieKatherine Levie More articles by this author , Fernando CaumontFernando Caumont More articles by this author , Timothy BrandTimothy Brand More articles by this author , Inger RosnerInger Rosner More articles by this author , Sean StroupSean Stroup More articles by this author , Joseph SterbisJoseph Sterbis More articles by this author , Jennifer CullenJennifer Cullen More articles by this author , and Christopher PorterChristopher Porter More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1009AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Management of patients with intermediate risk (IR) prostate cancer (PCa) based on PSA elevation but with Gleason 3+3 disease remains elusive; some authors have suggested that many could be offered active surveillance (AS). This study evaluated time to definitive treatment (DT) for PCa patients with IR (defined by PSA alone), low risk (LR) and favorable intermediate-risk (FIR) patients. METHODS A retrospective cohort study was performed from the Center for Prostate Disease Research (CPDR) multi-center national database between 1989-2013. Men ≤75 y/o with ≤ cT2a, Gleason ≤ 3+4 PCa, and PSA < 20, were included. We stratified patients into LR (defined by NCCN criteria), FIR (defined as Gleason ≤ 3+4, PSA <10) and IR PCa (defined by NCCN LR criteria, except PSA 10-20). The study population was restricted to men on AS, defined as men who received no definitive treatments in the first 12 months following diagnosis. The primary outcome was progression to DT among patients on AS. Time to DT was compared between the three comparison groups using Kaplan-Meier survival curves and the log-rank test. RESULTS Of 4,244 eligible men, there were 3,005 LR, 337 IR, and 902 FIR patients. Management on AS in the CPDR cohort was 16.1%, 10.6%, and 7.9% for LR, IR, and FIR respectively. Age at diagnosis was similar: 64.1 for LR, 65.7 for IR, and 63.3 years for FIR. Over one-quarter of patients were African American. PSA at diagnosis was 4.4 for LR, 13.7 for IR, and 5.5 for FIR patients. Median time to DT was 20.0, 17.2, and 20.6 months, for each risk group respectively. In patients undergoing initial AS, 23.3% LR, 25% IR, 36.6% FIR went on to DT during follow up; importantly, there were no significant differences between groups (Fig 1), p = 0.08. CONCLUSIONS In this large racially diverse, prospectively collected DB, AS remains underutilized in patients with low risk and intermediate risk disease. Patients with PSA defined IR disease who undergo AS progress to DT at similar rates as LR and FIR patients, and should be considered candidates for AS. We recognize long term follow up is needed to evaluate cancer progression in this cohort. Current efforts are underway to monitor trends in AS in recent years, as overtreatment rates continue to decrease. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e403 Advertisement Copyright & Permissions© 2018MetricsAuthor Information John Burns More articles by this author Lauren Hurwitz More articles by this author Katherine Levie More articles by this author Fernando Caumont More articles by this author Timothy Brand More articles by this author Inger Rosner More articles by this author Sean Stroup More articles by this author Joseph Sterbis More articles by this author Jennifer Cullen More articles by this author Christopher Porter More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP12-03 FAVORABLE INTERMEDIATE-RISK PROSTATE CANCER LEADS TO WORSE SURVIVAL COMPARED TO LOW-RISK PATIENTS DUE TO ADVERSE PATHOLOGY

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance I1 Apr 2018MP12-03 FAVORABLE INTERMEDIATE-RISK PROSTATE CANCER LEADS TO WORSE SURVIVAL COMPARED TO LOW-RISK PATIENTS DUE TO ADVERSE PATHOLOGY Hiten Patel, Mohit Gupta, Jeffrey Tosoian, H. Ballentine Carter, Alan Partin, and Jonathan Epstein Hiten PatelHiten Patel More articles by this author , Mohit GuptaMohit Gupta More articles by this author , Jeffrey TosoianJeffrey Tosoian More articles by this author , H. Ballentine CarterH. Ballentine Carter More articles by this author , Alan PartinAlan Partin More articles by this author , and Jonathan EpsteinJonathan Epstein More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.390AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Intermediate-risk (IR) prostate cancer is a heterogenous classification. While potential favorable criteria have been proposed to guide treatment decisions, recent evidence suggests rates of adverse pathology are not comparable to low-risk (LR) patients. Preoperative clinical stage and Grade Group (GG) on needle biopsy are often upstaged or upgraded on surgical pathology. Therefore, we aimed to quantify the rate of adverse surgical pathology and implications for survival for patients with favorable IR versus LR prostate cancer. METHODS The National Cancer Database was queried to identify patients undergoing radical prostatectomy (RP) with data on biopsy and surgical pathology from 2009-2013. Baseline and pathologic outcomes were compared for patients meeting clinically LR (GG1(3+3), ≤cT2a, PSA<10) or GG2(3+4) IR (GG2, ≤cT2b, PSA<20) disease. Adverse pathology was defined as ≥GG3(4+3), seminal vesicle invasion (pT3b), or lymph node metastasis (pN1)). Various strata and definitions from the literature were explored including the Memorial Sloan Kettering definition (MSK; ≤GG2 with only one IR factor including GG2, cT2b, or PSA 10-20). Log-binomial regression compared rates of adverse pathologic findings while logistic regression assessed predictors. Kaplan-Meier survival curves and adjusted Cox proportional hazards regression models compared overall survival (OS) between GG2 IR and LR groups as well as the impact of adverse pathology for GG2 IR patients. RESULTS A total of 3,519 (6.8%) of 51,688 LR and 8,888 (20.8%) of 42,720 GG2 IR patients included were found to have adverse pathologic findings (RR 3.06 (95%CI 2.95-3.17; p<0.001)), largely given by GG3 disease on surgical pathology. PSA and number of positive cores were significant predictors of adverse pathology but stratification minimally impacted the absolute rate. Results were similar for the MSK definition while restriction to GG1 IR patients led to a reduced increase in adverse pathology (RR 2.00 (1.86-2.16); p<0.001). GG2 IR patients had worse OS compared to LR patients in adjusted models (HR 1.25 (1.10-1.43; p=0.001)). Additionally, the presence of adverse pathology led to worse OS in the GG2 IR group (HR 1.26 (95% CI 1.03-1.54; p=0.023)). CONCLUSIONS Adverse pathology is observed at a three-fold higher rate for patients classified as favorable IR compared to LR. The presence of adverse pathologic findings led to worse survival for men in the favorable IR risk group; favorable IR men as a whole experienced worse survival relative to LR men. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e136 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Hiten Patel More articles by this author Mohit Gupta More articles by this author Jeffrey Tosoian More articles by this author H. Ballentine Carter More articles by this author Alan Partin More articles by this author Jonathan Epstein More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

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.

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.

Prospective analysis of 4,474 prostate biopsies to evaluate potential treatment management impact of combined clinical-genomic risk classification.

39 Background: Prior studies suggested integrated clinical-genomic risk grouping can more accurately prognosticate prostate cancer (PCa) outcome than NCCN clinical risk. We evaluated the potential for genomic testing to reclassify patients in a manner that could change management compared to NCCN risk groups. Methods: We evaluated 4,474 consecutive patients with PCa who received the Decipher Biopsy test between 01/2016-08/2017 and had information to determine NCCN risk. Genomic categorizations with the potential to change management were defined as NCCN very low/low to genomic intermediate or high (active surveillance to active treatment), NCCN favorable intermediate to genomic high (radiation therapy [RT] alone to RT plus androgen deprivation therapy [ADT]), NCCN unfavorable intermediate to genomic low (RT + ADT to RT alone), NCCN high risk to genomic low (RT + long term ADT to RT + short term ADT). Results: There were 927 NCCN low-risk, 2,427 intermediate, and 1,120 high-risk patients. Among NCCN low-risk, the incidence of genomic low, intermediate, and high risk was 58.7%, 25.0%, and 16.3% respectively, for NCCN intermediate it was 36.5%, 27.6%, and 35.8%, and for NCCN high risk it was 15.9%, 17.1%, and 67.1%. Management could have been changed in the 41.3% of NCCN low risk patients with intermediate or high genomic risk, 26.7% of favorable intermediate risk patients who had high genomic risk, 32.4% of unfavorable intermediate risk patients with low genomic risk, and 15.9% of high risk patients with low genomic risk. Conclusions: A slight majority (54%) of Decipher Biopsy users have NCCN intermediate-risk disease, likely reflecting a need for further prognostic information to refine recommendations in intermediate risk. Reclassification of NCCN groups by genomic risk was common and an integrated clinical-genomic risk system could have altered treatment recommendations in 41.3% of NCCN low, 26.7% of favorable intermediate, 32.4% of unfavorable intermediate risk, and 15.9% of high risk patients.

Heterogeneity in early oncologic outcomes among men with NCCN intermediate-risk prostate cancer treated with radical prostatectomy.

144 Background: The National Comprehensive Cancer Network (NCCN) risk classification scheme for prostate cancer (PCa) encompasses several definitions and has been shown to contain significant heterogeneity. Because patients possessing a single intermediate-risk (IR) feature may be regarded as ineligible for active surveillance (AS), we aimed to compare pathologic and early oncologic outcomes between those with low-risk (LR) and IR features based on the number of criteria met. Methods: We queried the National Cancer Database (NCDB) to identify men with NCCN LR (cT1-T2a, prostate-specific antigen [PSA] &lt; 10 ng/mL, and Gleason score (GS)≤6) and IR PCa diagnosed from 2010-2014 who were treated with radical prostatectomy (RP). Patients with IR PCa were stratified based on a single factor: clinical stage (cT2b-T2c), PSA (10-20 ng/mL), GS 3+4, or GS 4+3 alone. The pathologic outcomes including any Gleason upgrade, and adverse pathology (primary Gleason 4 or ≥pT3 at RP), and receipt of adjuvant radiation therapy (RT) were compared between the LR and IR groups. Odds ratios for pathologic outcomes and receipt of adjuvant RT were computed using logistic regression analyses. Results: Of 181,847 men treated with RP, we identified 30.7% and 37.1% with LR and IR PCa, respectively. Of 67,623 with IR PCa, 4,075 (6%) were due to clinical stage alone, 5,004 (7.4%) by PSA, 43,409 (64.2%) by GS 3+4, and 15,135 (22.4%) by GS 4+3. Patients meeting IR by clinical stage alone had similar risks of adverse pathology as LR patients (OR 1.03, 95%CI 0.94-1.13, p = 0.49). In contrast, those meeting IR by PSA alone had higher risks of adverse pathology compared with LR individuals (OR 2.20, 95%CI 2.05-2.36, p &lt; 0.001). Moreover, receipt of adjuvant RT was similar among LR and IR patients by clinical stage alone (p = 0.62), and higher among patients meeting IR by PSA alone (OR 2.99, 95% CI 2.43-3.69, p &lt; 0.001). Conclusions: Based on national cancer registry data, early outcomes among men meeting the NCCN IR definition for PCa are heterogeneous. IR patients by clinical stage alone had similar rates of adverse pathology as did LR group. Broadened eligibility for AS should be considered to include those meeting favorable IR definitions.

National Comprehensive Cancer Network® Favorable Intermediate Risk Prostate Cancer—Is Active Surveillance Appropriate?

We compared pathological and biochemical outcomes after radical prostatectomy in patients at favorable intermediate risk who fulfilled current NCCN® (National Comprehensive Cancer Network®) Guidelines® for active surveillance criteria to outcomes in patients who met more traditional criteria for active surveillance. We queried our institutional review board approved prostate cancer database for patients who met NCCN criteria for very low risk (T1c, Grade Group 1, 3 or fewer of 12 cores, 50% or less core volume and prostate specific antigen density less than 0.15 ng/ml), low risk (T1-T2a, Grade Group 1 and prostate specific antigen less than 10 ng/ml) or favorable intermediate risk (major pattern grade 3 and less than 50% positive biopsy cores) and who had 1 intermediate risk factor, including T2b/c, Grade Group 2 or prostate specific antigen 10 to 20 ng/ml. Men at intermediate risk who did not meet favorable criteria were labeled as being at unfavorable intermediate risk. Patients at favorable intermediate risk were compared to those at very low and low risk, and those at unfavorable intermediate risk to identify differences in rates of adverse pathological findings at radical prostatectomy, including Gleason score Grade Group 3-5, nonorgan confined disease or nodal involvement. Time to biochemical recurrence was compared among the groups using Cox regression. A total of 3,686 patients underwent radical prostatectomy between January 1, 2014 and December 31, 2015. Of these men 1,454, 250 and 1,362 fulfilled the criteria for low, favorable intermediate and unfavorable intermediate risk, respectively. The rate of adverse pathological findings in favorable intermediate risk cases was significantly higher than in low risk cases and significantly lower than in unfavorable intermediate risk cases (27.4% vs 14.8% and 48.5%, respectively, each p <0.001). Time to biochemical recurrence differed significantly among the risk groups (p <0.001). Relative to men at low risk those at favorable intermediate risk represent a distinct group. Care should be taken when selecting these patients for active surveillance and monitoring them once they are in an active surveillance program.

Brachytherapy monotherapy may be sufficient for a subset of patients with unfavorable intermediate risk prostate cancer

Purpose/objective(s)Brachytherapy (BT) monotherapy is a well-established treatment modality for favorable intermediate risk (FIR) prostate cancer. However, patients with unfavorable intermediate risk (UIR) disease are often recommended trimodality therapy involving BT, androgen deprivation therapy (ADT), and external beam radiation therapy (EBRT). We sought to investigate the relative benefit of supplemental therapies (ADT and/or EBRT) for FIR and UIR prostate cancer in a large dataset. Materials/methodsWe identified 3,723 patients with intermediate risk prostate cancer treated with BT between 1997 and 2013, including 1,989 and 1,734 patients with FIR and UIR disease, respectively. For the FIR cohort, Fine and Gray’s competing risks regression model was used to evaluate whether there was a difference in prostate cancer specific mortality (PCSM) between BT vs. BT + supplemental therapy (ADT, EBRT, or both). For the UIR cohort, this regression model was used to evaluate whether supplemental ADT, EBRT, or both decreased PCSM beyond BT alone. Both regression models were adjusted for clinical and treatment-related factors. ResultsThe median follow-up periods were 7.7 years (interquartile range: 5.4–10.5) for the FIR cohort and 7.8 years (interquartile range: 5.3–10.6) for the UIR cohort. For the FIR cohort, there was no difference in PCSM between BT monotherapy vs. BT + supplemental therapy (adjusted hazard ratio [AHR] = 1.70; 95% CI: 0.46–6.29; P = 0.43). For the UIR cohort, supplemental EBRT (AHR = 2.66; 95% CI: 1.12–6.34; P = 0.03), ADT (AHR = 0.96; 95% CI: 0.38–2.43; P = 0.93), or both (AHR = 1.46; 95% CI: 0.42–5.01; P = 0.55) were not associated with improved PCSM compared with BT alone. ConclusionIn our analysis, supplemental therapies did not offer an improvement in PCSM compared with BT alone for FIR or UIR prostate cancers. Further prospective clinical trials are required to determine whether BT monotherapy may be sufficient for a subset of patients with UIR disease.

Comparison of Pathological and Oncologic Outcomes of Favorable Risk Gleason Score 3 + 4 and Low Risk Gleason Score 6 Prostate Cancer: Considerations for Active Surveillance

Recent NCCN® (National Comprehensive Cancer Network®) Guidelines® show that patients with biopsy Gleason score 3 + 4/Grade Group 2 but otherwise favorable features are active surveillance candidates. However, little is known about the long-term outcomes compared to that in men in the low risk Gleason score 6/Grade Group 1 group. We sought to clarify the risk of adverse features and oncologic outcomes in surgically treated, favorable Grade Group 2vs 1 cases. We queried our prospectively maintained radical prostatectomy database for all 8,095 patients with biopsy Grade Group 1 or 2 prostate cancer who otherwise fulfilled the NCCN low risk definition of prostate specific antigen less than 10 ng/ml and cT2a or less, and who underwent radical prostatectomy from 1987 to 2014. Multivariable logistic regression and Kaplan-Meier methods were used to compare pathological and oncologic outcomes. Organ confined disease was present in 93.9% and 82.6% of Grade Group 1 and favorable intermediate risk Grade Group 2 cases while seminal vesicle invasion was noted in 1.7% and 4.7%, and nodal disease was noted in 0.3% and 1.8%, respectively (all p <0.0001). On multivariable logistic regression biopsy proven Grade Group 2 disease was associated with a threefold greater risk of nonorgan confined disease (OR 3.1, 95% CI 1.7-5.7, p <0.001). The incidence of late treatment (more than 90 days from surgery) in Grade Group 1 vs 2 was 3.1% vs 8.5% for hormonal therapy and 6.0% vs 12.2% for radiation (p <0.001). In the Grade Group 1 vs 2 cohorts the 10-year biochemical recurrence-free survival rate was 88.9% vs 81.2% and the 10-year systemic progression-free survival rate was 99% vs 96.5% (each p <0.001). Men at favorable risk with Grade Group 2 disease who are considering active surveillance should be informed of the risks of harboring adverse pathological features which impact secondary therapies and an increased risk of cancer progression.

Pathologic Outcomes of Gleason 6 Favorable Intermediate-Risk Prostate Cancer Treated With Radical Prostatectomy: Implications for Active Surveillance.

The safety of active surveillance (AS) for Gleason 6 favorable intermediate-risk (FIR) prostate cancer is unknown. To provide guidance, we examined the incidence and predictors of upgrading or upstaging for Gleason 6 FIR patients treated with radical prostatectomy. We identified 2807 men in the National Cancer Database diagnosed from 2010 to 2012 with Gleason 6 FIR disease (<50% positive biopsy cores [PBC] with either prostate-specific antigen [PSA] of 10-20 ng/mL or cT2b-T2c disease) treated with radical prostatectomy. Logistic regression was used to identify predictors of upgrading (Gleason 3+4 with tertiary Gleason 5 or Gleason≥4+3) or upstaging (pT3-4/N1). Fifty-seven percent of the cohort had PSA of 10 to 20 ng/mL; 25.5% patients with PSA of 10 to 20 ng/mL and 12.4% with cT2b to T2c disease were upgraded or upstaged. In multivariable analysis, predictors of upgrading or upstaging included increasing age (P= .026), PSA (P= .001), and percent PBC (P< .001), and black race versus white (P= .035) for patients with PSA of 10 to 20 ng/mL and increasing PSA (P=.001) and percent PBC (P< .001) for patients with cT2b to T2c disease. Men with PSA of 15.0 to 20.0 ng/mL or 37.5% to 49.9% PBC with PSA of 10 to 20 ng/mL had >30% risk of upgrading or upstaging, whereas cT2b to T2c patients with<12.5% PBC or PSA<5.0 ng/mL had<10% risk. We found that Gleason 6 FIR patients with cT2b to T2c tumors had a low risk of harboring higher grade or stage disease and would be reasonable AS candidates, whereas patients with PSA of 10 to 20 ng/mL had a high risk and might generally be poor AS candidates.

Modified risk stratification grouping using standard clinical and biopsy information for patients undergoing radical prostatectomy: Results from SEARCH.

Prostate cancer is a heterogeneous disease, and risk stratification systems have been proposed to guide treatment decisions. However, significant heterogeneity remains for those with unfavorable-risk disease. This study included 3335 patients undergoing radical prostatectomy without adjuvant radiotherapy in the SEARCH database. High-risk patients were dichotomized into standard and very high-risk (VHR) groups based on primary Gleason pattern, percentage of positive biopsy cores (PPBC), number of NCCN high-risk factors, and stage T3b-T4 disease. Similarly, intermediate-risk prostate cancer was separated into favorable and unfavorable groups based on primary Gleason pattern, PPBC, and number of NCCN intermediate-risk factors. Median follow-up was 78 months. Patients with VHR prostate cancer had significantly worse PSA relapse-free survival (PSA-RFS, P < 0.001), distant metastasis (DM, P = 0.004), and prostate cancer-specific mortality (PCSM, P = 0.015) in comparison to standard high-risk (SHR) patients in multivariable analyses. By contrast, there was no significant difference in PSA-RFS, DM, or PCSM between SHR and unfavorable intermediate-risk (UIR) patients. Therefore, we propose a novel risk stratification system: Group 1 (low-risk), Group 2 (favorable intermediate-risk), Group 3 (UIR and SHR), and Group 4 (VHR). The c-index of this new grouping was 0.683 for PSA-RFS and 0.800 for metastases, compared to NCCN-risk groups which yield 0.666 for PSA-RFS and 0.764 for metastases. Patients classified as VHR have markedly increased rates of PSA relapse, DM, and PCSM in comparison to SHR patients, whereas UIR and SHR patients have similar prognosis. Novel therapeutic strategies are needed for patients with VHR, likely involving multimodality therapy.

Incidence and Predictors of Upgrading and Upstaging Among 10,000 Patients with Gleason 3+4 Favorable Intermediate-Risk Prostate Cancer: Implications for Active Surveillance

Whether active surveillance can be safely offered to patients with intermediate-risk prostate cancer, particularly those with Gleason 3+4 favorable intermediate-risk (FIR) disease, is unknown. We studied this question by examining the incidence and predictors of upgrading and upstaging among patients with Gleason 3+4 FIR disease. We identified 10,089 patients in the National Cancer Database diagnosed from 2010 through 2012 with Gleason 3+4, PSA<10 ng/mL, and cT1c-2a prostate cancer with <50% positive biopsy cores (PBC) without clinical evidence of nodal or metastatic disease who were treated with radical prostatectomy. Multiple logistic regression was used to examine factors associated with upgrading (pathological Gleason 4+3 or 8-10) or upstaging (pT3-4 or pN1). 27.7% of all Gleason 3+4 FIR patients (2,793) were upgraded or upstaged (15.6% upgraded and 17.0% upstaged). On multivariable analysis, predictors of upgrading or upstaging include higher PSA, percentage of PBC, and cT stage, as well as older age (p<0.001 for all), but not Black race (p=0.651). When stratified into ordinal variables, PSA 8.1-9.9 ng/mL vs. 2.1-4.0 ng/mL (AOR 1.98, 34.9% vs. 21.4%); 37.5-49.9% vs. <12.5% PBC (AOR 1.77, 34.2% vs. 22.4%); cT2a vs. cT1c stage (AOR 1.32, 31.8% vs 27.1%); and highest quartile age (≥67) vs. lowest (≤55; AOR 1.45, 32.7% vs. 22.3%) were associated with increased risk of upstaging or upgrading (p<0.001 for all). 40.3% of men age ≥67 with 37.5-49.9% PBC were upgraded or upstaged. Overall, just over 1 in 4 Gleason 3+4 FIR patients were upgraded or upstaged after radical prostatectomy. Younger patients with low PBC, low PSA, and cT1c stage have a lower risk of harboring higher grade or stage disease and may be candidates for active surveillance. However, models based on widely available clinical information are insufficient for predicting the risk of more advanced disease, and research is necessary into developing and incorporating additional tools, including magnetic resonance imaging and genomic tests.

Patterns of Daily Practice of Hormone Therapy in Unfavorable and Favorable Intermediate-Risk Prostate Cancer: Results of the French PROACT Survey

The management of intermediate-risk (IR) prostate cancer (PCa) remains controversial for a subgroup of patients considered as heterogeneous in terms of prognosis. For unfavorable or favorable-IR PCa optimal therapy approach remains to be defined. Two randomized trials have shown improved biochemical control outcomes using external beam radiation therapy (EBRT) and hormone therapy (HT) over EBRT alone. However, physician’s decision to propose HT is not based on a robust rational for a routine practice. Thus, we decided, as academic and private group, to conduct the PROACT survey on pattern and preferences of daily practice in unfavorable and favorable IR PCa patients. The web-questionnaire was distributed to the GETUG, French radiotherapy and the French Association of Urology members. Responses from individual members were registered between January and December 2016. The questionnaire included 4 sections to describe: (i) specialists who prescribe treatments, decisions validation manner and use of guidelines; (ii) definition of IR subsets of patients; (iii) EBRT parameters and the choice of type/duration/sequence of HT and the prescribed drugs; (iv) cardiovascular (CV) and metabolic initial evaluation and follow-up practice. Among the 82 responses recorded, 79 (96%) were radiation oncologists from private or anti-cancer center (72%). HT and irradiation technique/dose/volumes is validated in a specific board meeting in only 45% and 54% of the centers. For prognosis, 76% of the centers declared to identify a subset of IR-patients for a dedicated strategy. The majority of centers consider PSA>15 (77%) and/or Gleason 4+3 (87%) as the main parameters for unfavorable IR definition. Overall, 41% of the centers declared to perform systematically a CV evaluation before HT prescription while 61% take into account the CV history/status to define the type of HT. In addition, CV status (80%) and age (39%) were declared as the main parameters for a specific drug choice. LHRH agonists are more frequently prescribed in both favorable (70%) and unfavorable (98%) IR. EBRT following hypofractionated schedules is used in only 10% and 14% of the centers and pelvic irradiation in 59% and 18% of the centers for unfavorable and favorable IR-patients, respectively. In terms of follow-up, 80%, 70% and 77% of the centers declared to systematically take into account patients’ weight, lipidic profile and CV status, respectively for follow-up under HT. To our knowledge this is the first survey on the patterns of practice of HT in IR prostate cancer. PROACT survey indicate that ¾ of the French centers declare to identify a subset of unfavorable IR-patients for a specific management. Only 10% of the centers use hypofractionated schedules (2-4Gy/fraction) and half of them include pelvic nodes for unfavorable IR cases. CV status of the patients is considered by the majority of centers as the main factor to determine the type of the drug to use and follow-up after therapy.

Does Second Review of Prostate Needle Biopsy Pathology Impact Radiation Therapy Management? A Tertiary Cancer Center Study

Prostate cancer (PC) therapy options are determined by patient risk stratification, based on Gleason score (GS), PSA and clinical staging. Studies have reported GS interobserver variability between pathologists. It is unclear how these differences impact radiation oncology-related recommendations. We aim to determine the frequency of diagnostic discordance between outside pathologists (OP) and specialized urologic pathologists (UP), and impact on active surveillance (AS) or radiation (RT) recommendations. 208 second opinion needle prostate biopsy pathology reviews were performed by UP at our institution in 2016. Our cohort consisted of 154 cases after excluding those with inadequate specimens, lack of initial pathology report, metastatic disease, and history of local therapy. Number of cores involved and highest GS reported at our institution by UP were compared to those reported by OP. NCCN risk groups were determined for patients with available PSA and cT classification (n=130). Risk groups included low (LR), favorable intermediate (FIR), unfavorable intermediate (UIR) and high risk (HR). FIR >75 yo and all LR were considered candidates for AS. LR and FIR were eligible for EBRT or brachytherapy alone (BA). FIR and UIR were eligible for RT with short term androgen deprivation therapy (EBRT + ST-ADT) +/- brachytherapy boost (BB) for only UIR. HR was eligible for EBRT with long term ADT (LT-ADT) +/- BB. Prostate size and IPSS were available to determine BA/BB eligibility in 112 patients. The agreement of treatment options between institutions was tested by McNemar’s exact tests. Discrepancy in highest GS was noted in 25% of cases. 6/12 cases initially reported as negative for cancer were identified to have PC. 29% of cases with PC had changes in % positive cores. NCCN risk group changed based on UP review in 25% (n=32) of cases, upgrading 34% and downgrading 66% of these patients. After UP review, the following patients were not found suitable for initial eligible treatment: 7% initially eligible for AS, 9% for BA, 7% for EBRT, 18% for EBRT + ST-ADT, 24% for EBRT + ST-ADT +BB, 31% for RT + LT-ADT and 29% for EBRT + LT-ADT +BB. Based on UP review, 10 new patients out of the total cohort (8%) were eligible for AS, 5 (4%) for BA, 14 (11%) for EBRT, 12 (9%) for EBRT + ST-ADT, 7 (5%) for EBRT + ST-ADT+ BB and 2 (2%) for EBRT + LT-ADT. 8 (6%) became eligible for brachytherapy (6 for BA and 2 for EBRT + ST-ADT+BB), but found to be poor candidates based on IPSS or prostate size. There was a change in treatment eligibility for 25% of the entire cohort. McNemar’s exact test showed UP review significantly differed impacting eligibility for EBRT + LT ADT (p=0.02) and EBRT alone (p=0.03) but not eligibility for AS (p=0.09), BA (p=0.12), EBRT + ST-ADT (p=0.66) or EBRT + ST-ADT + BB (p=1.0). UP review of prostate biopsies impacts risk groups, modifying RT recommendations. Second pathology review by a UP should be strongly considered prior to final treatment decisions for PC patients.

Comparison of Toxicities in High Dose Rate Versus Low Dose Rate Brachytherapy as Monotherapy in Patients with Low to Favorable Intermediate Risk Prostate Cancer

The purpose of our study was to compare acute and late toxicities of high dose rate (HDR) brachytherapy and low dose rate (LDR) permanent iodine or palladium seeds as monotherapy in patients with low and favorable intermediate risk prostate cancer. We retrospectively examined patients with biopsy proven, low to favorable intermediate risk prostate cancer treated with interstitial brachytherapy monotherapy from 1998-2016 at a single institution. Patients selected were restricted to T stage ≤ T2c, Gleason score ≤7, and prostate specific antigen (PSA) less than 20 ng/ml. For each case of prostate brachytherapy, needles/seeds were implanted transperineally via trans-rectal ultrasound guidance. Dose for LDR was 145 Gy and HDR was 27 Gy in 2 fractions. The Common Toxicity Criteria scale, version 2.0 and 3.0 were used to score the acute (<12 months after brachytherapy) and late (≥ 12 months after brachytherapy) toxicities. Chi square analysis tested for associations between toxicity and treatment technique. Logistic regression was used in multivariable analyses (MVA). A total of 572 patients were included, including 97 treated with HDR using 192iridium (192Ir), and 475 treated with LDR using 125iodine (125I) or 103palladium (103Pd). The median follow up time was 9.2months (range 3.1-145.3) for HDR patients and 53.1 months (range 0.2-198.6) for LDR patients. The two treatment groups were well-balanced with respect to age, T stage, ethnicity, and implanted prostate gland volume. A majority of patients had T1c disease and pretreatment PSA less than 10 ng/ml. 69% of HDR patients had Gleason score of 7 while 2.5% of LDR patients had Gleason score of 7. On univariate analysis, HDR brachytherapy was associated with lower rate of grade 2+ acute GU toxicity (14% vs 38%, p <0.0001) and grade 2+ late GU toxicity (10% vs 31%, p< 0.0001). Acute GI toxicity was low at 3% for both HDR and LDR; late GI toxicity were 6% and 7% (p= 0.63) for HDR and LDR, respectively. In MVA, only LDR was independently associated with increased risk of grade 2+ acute GU toxicity (OR 2.4, 95% CI 1.1-5.3), but it was no longer associated with increased risk of grade 2+ late GU toxicity (OR 1.0, 95% CI 0.5-2.3). MVA demonstrated no difference between the two treatment methods with regard to acute or late GI toxicity. Acute and late GI toxicity was rare in patients treated with brachytherapy. The use of HDR brachytherapy as monotherapy was associated with a significantly lower risk of grade 2+ acute GU toxicity but similar grade 2+ late GU toxicity compared to LDR. Our results suggest HDR may be the preferred brachytherapy option in patients with clinically localized prostate cancer due to the better acute safety profile.

Lack of Benefit From the Addition of External Beam Radiation Therapy to Brachytherapy for Intermediate- and High-risk Prostate Cancer

A recent randomized controlled trial demonstrated that the addition of external beam radiation therapy (EBRT) to brachytherapy did not improve progression-free survival in select patients with intermediate-risk prostate cancer. We evaluated whether the addition of EBRT to brachytherapy improves prostate cancer-specific mortality (PCSM) for intermediate- and high-risk disease using a large national database. We identified 5836 patients in the Surveillance, Epidemiology, and End Results-Medicare linked database with a diagnosis of National Comprehensive Cancer Network intermediate-risk (Gleason score 7, prostate-specific antigen 10-20ng/mL, or stage cT2b-T2c) or high-risk (Gleason score 8-10 or prostate-specific antigen >20ng/mL and stage≤cT3a) prostate cancer who had undergone brachytherapy, with or without EBRT and androgen deprivation therapy (ADT). Patients were diagnosed from 2004 through 2009. Intermediate-risk patients with Gleason score ≤3+4 and 1 intermediate-risk factor were considered favorable and all others unfavorable. We used multivariable Fine-Gray competing risks regression to study PCSM while adjusting for sociodemographic and clinical factors and ADTuse. Overall, 50.3% of intermediate- and high-risk patients who received brachytherapy and EBRT did not have significantly improved PCSM compared with that of the patients who received brachytherapy alone (adjusted hazard ratio [AHR] 1.46, 95% confidence interval [CI] 0.69-3.11; P=.322; 5-year PCSM 2.4% vs 1.0%). This lack of benefit was seen among favorable intermediate-risk (AHR 2.66, 95% CI 0.93-7.62, P=.069; 5-year PCSM 1.3% vs 0.6%), unfavorable intermediate-risk (AHR 0.68, 95% CI 0.16-2.96, P=.612; 5-year PCSM 1.0% vs 1.2%), and high-risk (AHR 1.82, 95% CI 0.67-4.98, P=.242; 5-year PCSM 5.3% vs 2.1%) subgroups. These results suggest that certain patients with intermediate- or high-risk prostate cancer treated with brachytherapy might not benefit from the addition of EBRT. A randomized controlled trial of brachytherapy plus ADT with or without EBRT for unfavorable intermediate- and favorable high-risk organ-confined prostate cancer should be undertaken.

Identifying intermediate-risk candidates for active surveillance of prostate cancer

PurposeAlthough already established for very-low and low-risk (LR) prostate cancer (PCa), controversy remains around offering active surveillance (AS) to men with intermediate-risk (IR) PCa. As IR represents a broad spectrum of disease biology, there is a critical need to define eligibility criteria that will enable both patient and physician to accept AS as the best balance of competing risks. In this study, we aimed to identify predictors of progression to enable optimal patient selection. Materials and methodsIn our AS cohort, men were assigned to risk categories according to the National Comprehensive Cancer Network (NCCN favorable and NCCN unfavorable) and the CAPRA classifications. Clinical, biochemical and pathological characteristics, progression to definitive invasive treatment, and pathologic progression on follow-up biopsies were compared among these groups. A multivariate Cox regression model was used to identify independent predictors of progression on AS. ResultsAS was the initial management option for 651 men, including 144 with IR PCa. During the median follow-up of 4.5 years (range: 0.6–19.1), 259 patients (39.7%) underwent definitive treatment. Further, 5- and 10-year predicted rates of intervention for IR patients were 50% and 66%, respectively. Treatment rates were no different between the NCCN LR and NCCN IR groups, but were higher in CAPRA IR compared to CAPRA LR groups (P = 0.025). NCCN unfavorable IR patients had a twofold increased risk of definitive intervention compared to favorable IR (hazard ratio [HR] = 2.07; 95% CI: 1.17–3.65; P = 0.01). In the entire cohort, the percentage of biopsy cores positive (continuous variable; P = 0.006) and ISUP grade 2 or higher on initial biopsy (P = 0.027) were independent predictors of cessation of AS on multivariate analysis. In the intermediate group, only the percentage of positive biopsy cores was an independent predictor (P = 0.021) of AS cessation. Only 1 IR patient developed metastatic disease (0.7%). Actuarial overall survival at 5 and 10 years was 98.6% and 94.1%, respectively. There were 2 PCa deaths at 18.7 and 19.1 years of follow-up. ConclusionIn all AS, increasing percentage of core involvement and presence of Gleason pattern 4 are predictors of increased risk of progression. For IR patients, the NCCN favorable criteria and CAPRA score predict those more likely to remain on AS.

Risk of Upgrading and Upstaging Among 10 000 Patients with Gleason 3 + 4 Favorable Intermediate-risk Prostate Cancer

BackgroundIt is unknown whether active surveillance can be safely offered to patients with Gleason 3+4 favorable intermediate-risk (FIR) prostate cancer. ObjectiveTo examine the incidence and predictors of upgrading and upstaging among patients with Gleason 3+4 FIR disease. Design, setting, and participantsThe study involved 10 089 patients in the National Cancer Database diagnosed from 2010 to 2012 with Gleason 3+4 disease, prostate-specific antigen (PSA) <10ng/ml, and cT1c-2a prostate cancer with <50% positive biopsy cores (PBCs) who underwent radical prostatectomy. Outcome measurements and statistical analysisLogistic regression was used to examine predictors of upgrading (pathologic Gleason ≥4+3 or tertiary Gleason 5 in a Gleason 7 tumor) or upstaging (pT3–4/N1). Results and limitationsSome 30.3% of Gleason 3+4 FIR patients were upgraded or upstaged. On multivariable analysis, predictors included higher PSA, percentage PBC, age, and cT2a versus cT1c (all p<0.001), but not black race (p=0.895). When stratified into ordinal variables, PSA 8.1–9.9 versus ≤4.0ng/ml (adjusted odds ratio [AOR] 1.93, 38.3% vs 24.4%), PBC 37.5–49.9% versus <12.5% (AOR 1.79, 37.8% vs 25.1%); highest age quartile (≥67 yr) versus lowest (≤55 yr; AOR 1.46, 35.7% vs 24.7%); and cT2a versus cT1c (AOR 1.33, 34.3% vs 29.8%) were associated with a higher risk of upgrading or upstaging (all p<0.001). Men with PBC <12.5% and PSA ≤4.0ng/ml had a 21.7% risk of more advanced disease. This increased to 44.3% for PBC 37.5–49.9% and PSA 8.1–9.9ng/ml. A limitation of the study is its retrospective nature. ConclusionsApproximately one in three patients with Gleason 3+4 FIR harbored disease of higher grade or stage. Younger patients with low percentage PBC and PSA and cT1c disease have a lower risk and may be candidates for active surveillance. However, widely available clinical information is insufficient for predicting the risk of more advanced disease, and the development and incorporation of additional tools, including magnetic resonance imaging and genomic tests, are necessary. Patient summaryNearly one-third of patients with Gleason 3+4 favorable intermediate-risk prostate cancer harbor disease of higher grade or higher stage than their biopsy and clinical examination suggest. These patients would therefore be poor candidates for active surveillance.

Unification of favourable intermediate‐, unfavourable intermediate‐, and very high‐risk stratification criteria for prostate cancer

To improve on the existing risk-stratification systems for prostate cancer. This was a retrospective investigation including 2 248 patients undergoing dose-escalated external beam radiotherapy (EBRT) at a single institution. We separated National Comprehensive Cancer Network (NCCN) intermediate-risk prostate cancer into 'favourable' and 'unfavourable' groups based on primary Gleason pattern, percentage of positive biopsy cores (PPBC), and number of NCCN intermediate-risk factors. Similarly, NCCN high-risk prostate cancer was stratified into 'standard' and 'very high-risk' groups based on primary Gleason pattern, PPBC, number of NCCN high-risk factors, and stage T3b-T4 disease. Patients with unfavourable-intermediate-risk (UIR) prostate cancer had significantly inferior prostate-specific antigen relapse-free survival (PSA-RFS, P < 0.001), distant metastasis-free survival (DMFS, P < 0.001), prostate cancer-specific mortality (PCSM, P < 0.001), and overall survival (OS, P < 0.001) compared with patients with favourable-intermediate-risk (FIR) prostate cancer. Similarly, patients with very high-risk (VHR) prostate cancer had significantly worse PSA-RFS (P < 0.001), DMFS (P < 0.001), and PCSM (P = 0.001) compared with patients with standard high-risk (SHR) prostate cancer. Moreover, patients with FIR and low-risk prostate cancer had similar outcomes, as did patients with UIR and SHR prostate cancer. Consequently, we propose the following risk-stratification system: Group 1, low risk and FIR; Group 2, UIR and SHR; and Group 3, VHR. These groups have markedly different outcomes, with 8-year distant metastasis rates of 3%, 9%, and 29% (P < 0.001) for Groups 1, 2, and 3, respectively, and 8-year PCSM of 1%, 4%, and 13% (P < 0.001) after EBRT. This modified stratification system was significantly more accurate than the three-tiered NCCN system currently in clinical use for all outcomes. Modifying the NCCN risk-stratification system to group FIR with low-risk patients and UIR with SHR patients, results in modestly improved prediction of outcomes, potentially allowing better personalisation of therapeutic recommendations.

External validation of a nomogram for identification of pathologically favorable disease in intermediate risk prostate cancer patients

To establish an external validation of the new nomogram from Gandaglia et al which provides estimates of the probability of pathological favorable disease in pre-operatively defined intermediate-risk PCa. Overall, 2928 intermediate-risk PCa patients according to the D'Amico classification undergoing RP and bilateral lymph node dissection in seven academic centres between 2000 and 2011. Pathologically favorable PCa was defined as low-grade organ-confined disease. The Receiver Operating Characteristic (ROC) curve was obtained to quantify the overall accuracy (Area Under the Curve, AUC) of the model to predict specimen-confined (SC) disease. Calibration curve was then constructed to illustrate the relationship between the risk-estimates obtained by the model and the observed proportion of SC disease. Kaplan-Meier method was used for PSA recurrence-free survival (PSA-RFS) assessment. Median age was 68 years. 10.6% patients finally presented pathologically favorable disease characteristics at RP. A higher PSAD (OR = 0.01; 95%CI = 0.00-0.04; P < 0.0001) and percentage of positive cores (OR = 0.97; 95%CI = 0.96-0.98; P < 0.0001) were associated with a reduced probability of favorable disease at RP in multivariate analysis. ROC curve analysis showed strongest accuracy of the model (AUC = 0.82; 95%CI = 0.79-0.84). Favorable PCa had a significantly better PSA recurrence-free survival rates as compared to unfavorable PCa after RP (94.2% vs 74.4% at 4 years, P < 0.0001). This external validation of the Gandaglia nomogram shows relevant accuracy with one out of ten patients in this intermediate risk PCa group with pathologically proven organ-confined disease. This validated risk calculator can help physician to distinguish favorable intermediate risk PCa that can be treated by conservative approach or safer nerve-sparing surgery.

MP20-02 NOVEL RISK STRATIFICATION GROUPING USING STANDARD CLINICAL AND BIOPSY INFORMATION FOR PATIENTS UNDERGOING RADICAL PROSTATECTOMY: RESULTS FROM SEARCH

You have accessJournal of UrologyProstate Cancer: Staging I1 Apr 2017MP20-02 NOVEL RISK STRATIFICATION GROUPING USING STANDARD CLINICAL AND BIOPSY INFORMATION FOR PATIENTS UNDERGOING RADICAL PROSTATECTOMY: RESULTS FROM SEARCH Zachary Zumsteg, Zinan Chen, Lauren Howard, Christopher Amling, William Aronson, Matthew Cooperberg, Christopher Kane, Martha Terris, Daniel Spratt, Howard Sandler, and Stephen Freedland Zachary ZumstegZachary Zumsteg More articles by this author , Zinan ChenZinan Chen More articles by this author , Lauren HowardLauren Howard More articles by this author , Christopher AmlingChristopher Amling More articles by this author , William AronsonWilliam Aronson More articles by this author , Matthew CooperbergMatthew Cooperberg More articles by this author , Christopher KaneChristopher Kane More articles by this author , Martha TerrisMartha Terris More articles by this author , Daniel SprattDaniel Spratt More articles by this author , Howard SandlerHoward Sandler More articles by this author , and Stephen FreedlandStephen Freedland More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.634AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer is a heterogeneous disease, and risk stratification systems have been proposed to guide treatment decisions and inform patient prognosis. However, significant heterogeneity remains, especially among those with high risk disease, and thus improved stratification is needed. METHODS Data on 3335 men, including 605 high risk, undergoing radical prostatectomy without adjuvant treatment were collected in the SEARCH database. Patients were grouped into five categories: low risk (biopsy Gleason 2-6, T1a-T2a, and PSA <10ng/ml), favorable intermediate risk (FIR), unfavorable intermediate risk (UIR), standard high risk (SHR), very high risk (VHR). Intermediate risk patients by NCCN guidelines (T2b or T2c, biopsy Gleason 7, or PSA 10-20ng/ml) were UIR if they had biopsy Gleason 4+3, ≥50% positive biopsy cores, or multiple intermediate-risk factors (T2b or T2c, biopsy Gleason 7, or PSA 10-20ng/ml), and FIR otherwise. High risk patients by NCCN guidelines (biopsy Gleason score 8-10, T3-T4, or PSA ≥20ng/ml) were VHR if they had primary Gleason 5, >50% positive biopsy cores, T3b-T4 or multiple high-risk factors (biopsy Gleason score 8-10, T3-T4, or PSA ≥20ng/ml), and SHR otherwise. Cox models were used to test the association between risk group and time to biochemical recurrence (BCR) and distant metastases (DM). Competing risks was used to test the association between risk group and prostate cancer-specific mortality (PCSM). Models were adjusted for age, race, year, and surgical center. RESULTS Median follow-up was 78 mo. Men with VHR disease had increased risk of BCR (p<0.001), DM (P=0.004), and PCSM (P=0.011) in comparison to SHR, but there were no differences in BCR, DM, or PCSM between SHR and UIR patients (p>0.4). FIR men had increased risk of BCR (HR 1.34, p=0.006) and DM (HR 2.42, p=0.035) compared to low risk men, but there was no difference in PCSM (p=0.17). Therefore, we propose a novel risk grouping: Group 1 (low risk), Group 2 (FIR), Group 3 (UIR and SHR), and Group 4 (VHR). These groups have markedly different outcomes, with 10 year DM rates of 0.7%, 2.8%, 6.9%, and 16.3% (p<0.001) for Groups 1-4 respectively, and 10 year PCSM of 0.3%, 1.9%, 3.3%, and 10.9% (P<0.001). The c-index of this grouping was 0.80 for DM vs. 0.76 for D'Amico risk groups. CONCLUSIONS Patients classified as VHR have increased rates of PSA relapse, DM, and PCSM in comparison to SHR patients, whereas UIR and SHR patients have similar prognosis. Novel therapeutic strategies are needed for patients with VHR, likely involving multimodality therapy. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e239 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Zachary Zumsteg More articles by this author Zinan Chen More articles by this author Lauren Howard More articles by this author Christopher Amling More articles by this author William Aronson More articles by this author Matthew Cooperberg More articles by this author Christopher Kane More articles by this author Martha Terris More articles by this author Daniel Spratt More articles by this author Howard Sandler More articles by this author Stephen Freedland More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...