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Very-high-risk (VHR) prostate cancer (PC) is an aggressive subgroup with high risk of distant disease progression. Systemic treatment intensification with abiraterone or docetaxel reduces PC-specific mortality (PCSM) and distant metastasis (DM) in men receiving external beam radiation therapy (EBRT) with androgen deprivation therapy (ADT). Whether prostate-directed treatment intensification with the addition of brachytherapy (BT) boost to EBRT with ADT improves outcomes in this group is unclear.This cohort study from 16 centers across 4 countries included men with VHR PC treated with either dose-escalated EBRT with ≥24 months of ADT or EBRT + BT boost with ≥12 months of ADT. VHR was defined by National Comprehensive Cancer Network (NCCN) criteria (clinical T3b-4, primary Gleason pattern 5, or ≥2 NCCN high-risk features), and results were corroborated in a subgroup of men who met Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trials inclusion criteria (≥2 of the following: clinical T3-4, Gleason 8-10, or PSA ≥40 ng/mL). PCSM and DM between EBRT and EBRT + BT were compared using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression.Among the entire cohort, 270 underwent EBRT and 101 EBRT + BT. After a median follow-up of 7.8 years, 6.7% and 5.9% of men died of PC and 16.3% and 9.9% had DM after EBRT and EBRT + BT, respectively. There was no significant difference in PCSM (sHR, 1.47 [95% CI, 0.57-3.75]; P = .42) or DM (sHR, 0.72, [95% CI, 0.30-1.71]; P = .45) between EBRT + BT and EBRT. Results were similar within the STAMPEDE-defined VHR subgroup (PCSM: sHR, 1.67 [95% CI, 0.48-5.81]; P = .42; DM: sHR, 0.56 [95% CI, 0.15-2.04]; P = .38).In this VHR PC cohort, no difference in clinically meaningful outcomes was observed between EBRT alone with ≥24 months of ADT compared with EBRT + BT with ≥12 months of ADT. Comparative analyses in men treated with intensified systemic therapy are warranted.

Key Points Question What is the optimal minimum duration of androgen deprivation therapy (ADT) when treating high-risk prostate cancer with high-dose radiotherapy? Findings This patient-level cohort study of 3 cohorts found a significant interaction between the type of high-dose radiotherapy (external beam radiotherapy with or without a brachytherapy boost) and optimal duration. Prolonging ADT for 18 to 28 months was associated with a 63% reduction in death or metastasis with external beam radiotherapy; when a brachytherapy boost was added, the nonlinear association between ADT and distant metastasis-free survival was broad and spanned 12 months. Meaning The findings of this cohort study suggest that patients receiving external beam radiotherapy alone may benefit from ADT durations of 18 months or more; if a brachytherapy boost is added, a duration of 18 months or possibly less may be optimal., Importance Radiotherapy combined with androgen deprivation therapy (ADT) is a standard of care for high-risk prostate cancer. However, the interplay between radiotherapy dose and the required minimum duration of ADT is uncertain. Objective To determine the specific ADT duration threshold that provides a distant metastasis-free survival (DMFS) benefit in patients with high-risk prostate cancer receiving external beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT). Design, Settings, and Participants This was a cohort study of 3 cohorts assembled from a multicenter retrospective study (2000-2013); a post hoc analysis of the Randomized Androgen Deprivation and Radiotherapy 03/04 (RADAR; 2003-2007) randomized clinical trial (RCT); and a cross-trial comparison of the RADAR vs the Deprivación Androgénica y Radio Terapía (Androgen Deprivation and Radiation Therapy; DART) 01/05 RCT (2005-2010). In all, the study analyzed 1827 patients treated with EBRT and 1108 patients treated with EBRT+BT from the retrospective cohort; 181 treated with EBRT and 203 with EBRT+BT from RADAR; and 91 patients treated with EBRT from DART. The study was conducted from October 15, 2020, to July 1, 2021, and the data analyses, from January 5 to June 15, 2021. Exposures High-dose EBRT or EBRT+BT for an ADT duration determined by patient-physician choice (retrospective) or by randomization (RCTs). Main Outcomes and Measures The primary outcome was DMFS; secondary outcome was overall survival (OS). Natural cubic spline analysis identified minimum thresholds (months). Results This cohort study of 3 studies totaling 3410 men (mean age [SD], 68 [62-74] years; race and ethnicity not collected) with high-risk prostate cancer found a significant interaction between the treatment type (EBRT vs EBRT+BT) and ADT duration (binned to, This cohort study explores associations between the duration of androgen deprivation therapy and distant metastasis-free survival in men undergoing external beam radiotherapy with and without a brachytherapy boost for treatment of high-risk prostate cancer.

Key Points Question Are external beam radiotherapy, with or without brachytherapy boost, or radical prostatectomy associated with differences in prostate cancer–specific mortality or distant metastasis outcomes in patients with high-risk prostate cancer after accounting for delivery of guideline-concordant multimodality therapy? Findings In this cohort study of 6004 men with high-risk prostate cancer and at least 1 additional adverse clinicopathologic feature, no differences in prostate cancer-specific mortality across treatment modalities were identified among patients who received guideline-concordant multimodality therapy, although differences in time to metastasis were observed. However, significant differences in prostate cancer–specific mortality were identified when guideline-concordant multimodality care was not delivered. Meaning These findings suggest that guideline-concordant multimodality care was associated with better prostate cancer–specific mortality outcomes for patients with high-risk prostate cancer., This cohort study assesses prostate cancer–specific mortality and distant metastasis outcomes among men with high-risk prostate cancer treated with radical prostatectomy or external beam radiotherapy with or without brachytherapy boost., Importance The optimal management strategy for high-risk prostate cancer and additional adverse clinicopathologic features remains unknown. Objective To compare clinical outcomes among patients with high-risk prostate cancer after definitive treatment. Design, Setting, and Participants This retrospective cohort study included patients with high-risk prostate cancer (as defined by the National Comprehensive Cancer Network [NCCN]) and at least 1 adverse clinicopathologic feature (defined as any primary Gleason pattern 5 on biopsy, clinical T3b-4 disease, ≥50% cores with biopsy results positive for prostate cancer, or NCCN ≥2 high-risk features) treated between 2000 and 2014 at 16 tertiary centers. Data were analyzed in November 2020. Exposures Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT), or EBRT plus brachytherapy boost (BT) with ADT. Guideline-concordant multimodal treatment was defined as RP with appropriate use of multimodal therapy (optimal RP), EBRT with at least 2 years of ADT (optimal EBRT), or EBRT with BT with at least 1 year ADT (optimal EBRT with BT). Main Outcomes and Measures The primary outcome was prostate cancer–specific mortality; distant metastasis was a secondary outcome. Differences were evaluated using inverse probability of treatment weight–adjusted Fine-Gray competing risk regression models. Results A total of 6004 men (median [interquartile range] age, 66.4 [60.9-71.8] years) with high-risk prostate cancer were analyzed, including 3175 patients (52.9%) who underwent RP, 1830 patients (30.5%) who underwent EBRT alone, and 999 patients (16.6%) who underwent EBRT with BT. Compared with RP, treatment with EBRT with BT (subdistribution hazard ratio [sHR] 0.78, [95% CI, 0.63-0.97]; P = .03) or with EBRT alone (sHR, 0.70 [95% CI, 0.53-0.92]; P = .01) was associated with significantly improved prostate cancer–specific mortality; there was no difference in prostate cancer–specific mortality between EBRT with BT and EBRT alone (sHR, 0.89 [95% CI, 0.67-1.18]; P = .43). No significant differences in prostate cancer–specific mortality were found across treatment cohorts among 2940 patients who received guideline-concordant multimodality treatment (eg, optimal EBRT alone vs optimal RP: sHR, 0.76 [95% CI, 0.52-1.09]; P = .14). However, treatment with EBRT alone or EBRT with BT was consistently associated with lower rates of distant metastasis compared with treatment with RP (eg, EBRT vs RP: sHR, 0.50 [95% CI, 0.44-0.58]; P

PURPOSE/OBJECTIVE(S) The use/prolongation of androgen deprivation therapy (ADT) with external beam radiotherapy (EBRT) improves distant metastasis outcomes in patients with high-risk prostate cancer. The optimal duration of ADT when adding a brachytherapy boost (EBRT+BT) remains unknown. MATERIALS/METHODS A total of 2935 patients who received treatment across 15 institutions between 2000-2014 were identified (1827 treated with EBRT and 1108 with EBRT+BT). Three broad ADT strata were defined: no ADT, 1-18 months ADT, and 18-36 months ADT. Fine-Gray competing risk regression models evaluating the association between differing ADT duration strata and time to distant metastasis (DM) were developed. Models were adjusted for ln (initial PSA), clinical T stage, Gleason grade group, age at treatment, treatment type, and interaction between ADT duration and treatment. A continuous, non-linear relationship between ADT duration and DM was investigated in the overall cohort and within the EBRT and EBRT+BT cohorts using a restricted cubic spline transformation with 4 knots. Splines were adjusted for the same covariates. RESULTS Median follow-up was 8 years (IQR, 5-11.3 years). ADT duration was significantly greater in patients treated with EBRT (median 18 months vs. 8 months, P < 0.001). A substantial proportion of patients did not receive any ADT (26.2% and 14.9% of those undergoing EBRT and EBRT+BT, respectively). Overall, DM rates were improved with adding 1-18 months of ADT or 18-36 months of ADT versus no ADT (sHR 0.66 and 0.43, respectively). DM rates were also lower after 18-36 months vs. 1-18 months (sHR 0.64). No significant interaction between treatment type and ADT duration was seen. Based on spline analysis, the optimal durations of ADT were 26 months for the total cohort and patients receiving EBRT and 22.5 months for patients receiving EBRT+BT. However, the incremental benefit of prolonged time to DM per month ADT added appears to be more pronounced in patients receiving EBRT than in those undergoing combined EBRT+BT treatment. CONCLUSION A clear relationship between ADT duration and DM risk following definitive radiotherapy in patients with HRPCa was seen, with durations of 18-36 months being associated with the lowest risk of DM. The lack of a significant interaction between ADT duration and treatment type implies this relationship persists even in patients receiving EBRT+BT. However, the magnitude of this benefit may differ, and prospective evidence seems warranted to determine the optimal duration of ADT in patients receiving of EBRT+BT.

INTRODUCTION AND OBJECTIVE:External beam radiotherapy (EBRT) with androgen deprivation therapy (ADT), EBRT with a brachytherapy boost (EBRT+BT) with ADT, and radical prostatectomy (RP) with or with...

Purpose Gleason score (GS) 10 disease is the most aggressive form of clinically localized prostate adenocarcinoma (PCa). The long-term clinical outcomes and overall prognosis of patients presenting with GS 10 PCa are largely unknown because of its rarity. Methods and Materials The study included 112 patients with biopsy-determined GS 10 PCa who received treatment with radical prostatectomy (RP, n = 26), external beam radiation therapy (EBRT, n = 48), or EBRT with a brachytherapy boost (EBRT-BT, n = 38) between 2000 and 2013. Propensity scores were included as covariates for comparative analysis. Overall survival, prostate cancer–specific survival, and distant metastasis–free survival (DMFS) were estimated by the Kaplan-Meier method with inverse probability of treatment weighting to control for confounding. Results The median follow-up period was 4.9 years overall (3.9 years for RP, 4.8 years for EBRT, and 5.7 years for EBRT-BT). Significantly more EBRT patients than EBRT-BT patients received upfront androgen deprivation therapy (98% vs 79%, P Conclusions To our knowledge, this is the largest series ever reported on the clinical outcomes of patients with biopsy-determined GS 10 PCa. These data provide useful prognostic benchmark information for physicians and patients. Aggressive therapy with curative intent is warranted, as >50% of patients remain free of systemic disease 5 years after treatment.

Key Points Question Is previously occult, nonlocalized (regional or metastatic) disease detected on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) associated with clinically significant outcomes in patients with high-risk and very high-risk prostate cancer? Findings In this cohort study of 5275 patients, a nomogram estimative of an individual’s risk of nonlocalized disease on PSMA PET/CT was significantly associated with long-term outcomes, including distant metastasis and prostate cancer–specific mortality. The nomogram performed favorably compared with other risk-stratification tools. Meaning These findings suggest that previously occult disease may be associated with outcomes in this patient population., This cohort study evaluates the prognostic significance of a nomogram that models an individual’s risk of nonlocalized upstaging on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and compares its performance with existing risk-stratification tools., Importance Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) can detect low-volume, nonlocalized (ie, regional or metastatic) prostate cancer that was occult on conventional imaging. However, the long-term clinical implications of PSMA PET/CT upstaging remain unclear. Objectives To evaluate the prognostic significance of a nomogram that models an individual’s risk of nonlocalized upstaging on PSMA PET/CT and to compare its performance with existing risk-stratification tools. Design, Setting, and Participants This cohort study included patients diagnosed with high-risk or very high-risk prostate cancer (ie, prostate-specific antigen [PSA] level >20 ng/mL, Gleason score 8-10, and/or clinical stage T3-T4, without evidence of nodal or metastatic disease by conventional workup) from April 1995 to August 2018. This multinational study was conducted at 15 centers. Data were analyzed from December 2020 to March 2021. Exposures Curative-intent radical prostatectomy (RP), external beam radiotherapy (EBRT), or EBRT plus brachytherapy (BT), with or without androgen deprivation therapy. Main Outcomes and Measures PSMA upstage probability was calculated from a nomogram using the biopsy Gleason score, percentage positive systematic biopsy cores, clinical T category, and PSA level. Biochemical recurrence (BCR), distant metastasis (DM), prostate cancer–specific mortality (PCSM), and overall survival (OS) were analyzed using Fine-Gray and Cox regressions. Model performance was quantified with the concordance (C) index. Results Of 5275 patients, the median (IQR) age was 66 (60-72) years; 2883 (55%) were treated with RP, 1669 (32%) with EBRT, and 723 (14%) with EBRT plus BT; median (IQR) PSA level was 10.5 (5.9-23.2) ng/mL; 3987 (76%) had Gleason grade 8 to 10 disease; and 750 (14%) had stage T3 to T4 disease. Median (IQR) follow-up was 5.1 (3.1-7.9) years; 1221 (23%) were followed up for at least 8 years. Overall, 1895 (36%) had BCR, 851 (16%) developed DM, and 242 (5%) died of prostate cancer. PSMA upstage probability was significantly prognostic of all clinical end points, with 8-year C indices of 0.63 (95% CI, 0.61-0.65) for BCR, 0.69 (95% CI, 0.66-0.71) for DM, 0.71 (95% CI, 0.67-0.75) for PCSM, and 0.60 (95% CI, 0.57-0.62) for PCSM (P

301 Background: The aim is to investigate the clinical significance of biochemical response after Androgen Deprivation Therapy (ADT) prior to high-dose-rate brachytherapy (HDR-BT) for early identification of patients at increased risk of recurrence. Measured outcomes included biochemical relapse free survival (bRFS), distant metastasis free survival (DMFS) and overall survival (OS). Methods: A total of 324 patients with high-risk Prostate Cancer (PCa) were identified in the Norwegian Radium Hospital brachytherapy database. Neo-adjuvant ADT was administered for 3-6 months, followed by two 10 Gy HDR-BT treatments to the prostate, each spaced by two weeks, followed by conformal external beam radiation to 50 Gy to the prostate gland and seminal vesicles. Total length of ADT ranged from 12 to 36 months. PSA (ng/mL) and testosterone values (T, nmol/L) after 3-6 months of neo-adjuvant ADT were measured. Kaplan Meier and Cox regression analyses were performed. Results: Median age at diagnosis was 66 years and median follow-up was 10 years. At last follow-up, 277 patients (85,2%) were alive, 10 patients (3.1%) had died of prostate cancer and 37 patients (11.4%) died of other causes. 24 patients (7.4%) had biochemical relapse and 9 patients (2.8%) had distant metastasis within the first 5 years. Patients with PSA > 1 after neo-adjuvant therapy had 4.3 (95%CI 1.7 to 11.1) higher odds of biochemical relapse within 5 years compared to patients with PSA < 1 (p = 0.002). ROC analysis confirmed that PSA < 1 had a prediction accuracy of 0.76 (sensitivity 68% and specificity 67%). T < 0.7 and PSA < 1 after neo-adjuvant therapy were associated with improved bRFS, DMFS and OS (p < 0.001). Neither the length of neo-adjuvant nor total ADT treatment impacted outcomes (p > 0.05). Conclusions: Dose intensification with 2 HDR-BT boosts resulted in excellent survival in our cohort. PSA > 1 after neo-adjuvant ADT may be able to predict patients at increased risk of relapse and worse OS and identify patients in whom increased monitoring and/or intervention is warranted. ADT > 1 year did not improve outcome, indicating that shorter course of ADT may be used.

208 Background: Treatment of high risk prostate cancer (HRPCa) with external beam radiotherapy (EBRT) plus brachytherapy (BT) boost (EBRT+BT) has been prospectively associated with lower rates of BCR, albeit potentially with increased toxicity, and retrospectively linked to decreased distant metastasis (DM) and PCa-specific mortality (PCSM) compared to EBRT alone. However, it is unclear whether patients who develop BCR following either approach have similar downstream oncologic outcomes. Methods: We identified 706 out of 3820 men with HRPCa treated at 13 institutions from 1998-2015 with EBRT (n=468/2134) or EBRT+BT (n=238/1686) who developed BCR. We compared rates of DM, PCSM, and all-cause mortality (ACM) after BCR between treatment groups using Fine-Gray competing risk regression. Models were adjusted for age, Gleason grade group, initial PSA (iPSA), clinical T stage, time-dependent use of systemic salvage, and interval to BCR using inverse probability of treatment weighting. Results: Median follow-up was 9.9 years from RT and 4.8 years from BCR. Groups were similar in age, iPSA, presence of ≥2 HR features, and median interval to BCR (3.3 years). Most men received neoadjuvant/concurrent androgen deprivation therapy (ADT), 92.5% and 91.0% for EBRT and EBRT+BT, respectively, though for a longer duration with EBRT (median 14.7 vs. 9.0 months, p=0.0012). Local and systemic salvage rates were 2.3% and 36.3% after EBRT, and 2.6% and 43.6% after EBRT+BT, respectively. Initial EBRT+BT was associated with significantly lower rates of DM after BCR (HR 0.48, 95% CI 0.36-0.64, p

Background The survival benefit of dose-escalation with High-Dose-Rate brachytherapy (HDR-BT) boost combined with External Beam Radiotherapy (EBRT) for the treatment of high-risk prostate cancer (PCa) remains debatable. We investigated 10-year PCa-specific mortality (PCSM) and overall mortality (OM) in high-risk patients treated with HDR-BT/EBRT (calculated EQD2 = 102 Gy) compared to EBRT alone (70 Gy). Methods HDR-BT boosts (10 Gy × 2) were given 2 weeks apart followed by 50 Gy conformal EBRT (2 Gy × 25) to the prostate and seminal vesicles. The HDR-BT/EBRT group (N:325) received Androgen Deprivation Therapy for a median duration of 2 years. The historical control group (N:296), received a median dose of 70 Gy (2 Gy × 35) to the prostate and seminal vesicles with lifelong Anti-Androgen Treatment. For each treatment group PCSM and OM were established by competing-risk analyses and Kaplan–Meier analyses respectively. Differences were evaluated by the logrank test. Independent associations were established by Cox regression analyses. Significance level set to p

Importance The optimal treatment for Gleason score 9-10 prostate cancer is unknown. Objective To compare clinical outcomes of patients with Gleason score 9-10 prostate cancer after definitive treatment. Design, Setting, and Participants Retrospective cohort study in 12 tertiary centers (11 in the United States, 1 in Norway), with 1809 patients treated between 2000 and 2013. Exposures Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy, or EBRT plus brachytherapy boost (EBRT+BT) with androgen deprivation therapy. Main Outcomes and Measures The primary outcome was prostate cancer–specific mortality; distant metastasis-free survival and overall survival were secondary outcomes. Results Of 1809 men, 639 underwent RP, 734 EBRT, and 436 EBRT+BT. Median ages were 61, 67.7, and 67.5 years; median follow-up was 4.2, 5.1, and 6.3 years, respectively. By 10 years, 91 RP, 186 EBRT, and 90 EBRT+BT patients had died. Adjusted 5-year prostate cancer–specific mortality rates were RP, 12% (95% CI, 8%-17%); EBRT, 13% (95% CI, 8%-19%); and EBRT+BT, 3% (95% CI, 1%-5%). EBRT+BT was associated with significantly lower prostate cancer–specific mortality than either RP or EBRT (cause-specific HRs of 0.38 [95% CI, 0.21-0.68] and 0.41 [95% CI, 0.24-0.71]). Adjusted 5-year incidence rates of distant metastasis were RP, 24% (95% CI, 19%-30%); EBRT, 24% (95% CI, 20%-28%); and EBRT+BT, 8% (95% CI, 5%-11%). EBRT+BT was associated with a significantly lower rate of distant metastasis (propensity-score-adjusted cause-specific HRs of 0.27 [95% CI, 0.17-0.43] for RP and 0.30 [95% CI, 0.19-0.47] for EBRT). Adjusted 7.5-year all-cause mortality rates were RP, 17% (95% CI, 11%-23%); EBRT, 18% (95% CI, 14%-24%); and EBRT+BT, 10% (95% CI, 7%-13%). Within the first 7.5 years of follow-up, EBRT+BT was associated with significantly lower all-cause mortality (cause-specific HRs of 0.66 [95% CI, 0.46-0.96] for RP and 0.61 [95% CI, 0.45-0.84] for EBRT). After the first 7.5 years, the corresponding HRs were 1.16 (95% CI, 0.70-1.92) and 0.87 (95% CI, 0.57-1.32). No significant differences in prostate cancer–specific mortality, distant metastasis, or all-cause mortality (≤7.5 and >7.5 years) were found between men treated with EBRT or RP (cause-specific HRs of 0.92 [95% CI, 0.67-1.26], 0.90 [95% CI, 0.70-1.14], 1.07 [95% CI, 0.80-1.44], and 1.34 [95% CI, 0.85-2.11]). Conclusions and Relevance Among patients with Gleason score 9-10 prostate cancer, treatment with EBRT+BT with androgen deprivation therapy was associated with significantly better prostate cancer–specific mortality and longer time to distant metastasis compared with EBRT with androgen deprivation therapy or with RP.

102 Background: Patients with Gleason score (GS) 9-10 prostate cancer (PCa) have a high risk of early biochemical recurrence (BCR). Salvage therapy options differ depending on the upfront management strategy. Patients who received upfront surgery (RP) may be curable with salvage external beam radiation therapy (EBRT). However those who underwent EBRT or EBRT with a brachytherapy boost (EBRT+BT) are less likely to receive local salvage therapy and are commonly treated with androgen deprivation therapy (ADT). In this study, we examine the risk of distant metastases (DM) and prostate-cancer specific mortality (PCSM) among patients with GS 9-10 PCa who had BCR following RP, EBRT, or EBRT+BT. Methods: 712 patients with GS 9-10 PCa treated between 2000-2013 at 12 institutions who had BCR were included (346 RP, 282 EBRT, 84 EBRT+BT). Time to DM and PCSM were compared between groups using Cox proportional hazards models with propensity score adjustment. Propensity scores were calculated using age, T-stage, PSA, and GS. Results: In patients who had a BCR, incidence rates of DM and PCSM after RP were 40% and 28%. Rates after EBRT were 60% and 46% and after EBRT+BT were 49% and 31%. Median times to DM and PCSM were 3.5 and 4.9 years after RP, 3.7 and 5.1 years after EBRT, and 3.3 and 6.8 years after EBRT+BT. The rates of local salvage RT and systemic salvage therapy among RP patients were 38% and 59%, respectively. Local and systemic salvage rates were 5% and 31% for EBRT patients and 5% and 28% for EBRT+BT patients. EBRT patients had a shorter time interval to DM compared with RP (HR 1.4, p = .02) and EBRT+BT (HR 1.9, p < .01). EBRT patients also had a shorter time interval to PCSM compared with RP (HR 1.5, p = .02). Conclusions: Among patients with GS 9-10 PCa who experience BCR after definitive management, those treated with EBRT have a shorter time interval to DM and PCSM compared with RP and EBRT+BT. While this analysis is confounded by the differential thresholds for diagnosing a BCR after different modalities, it does suggest that outcomes following BCR after EBRT+BT and RP are similar. It also suggests that extreme dose escalation delays the onset of DM and PCSM even after BCR, when compared with conventionally-dosed EBRT alone.

Purpose/Objective(s) To assess the effect on clinical outcomes of the addition of whole pelvis radiation (WPRT) to definitive prostate external beam radiation therapy (EBRT) or external beam radiation therapy plus brachytherapy boost (EBRT-BT) for patients with Gleason Score (GS) 9-10 prostate cancer (PCa), who are at high risk of having occult nodal metastases. Materials/Methods Nine-hundred-forty-two patients with biopsy-proven GS 9-10 PCa treated between 2000 and 2013 at 10 institutions (506 with EBRT and 436 with EBRT+BT) were included. 299 EBRT patients (59%) and 320 EBRT+BT patients (73.4%) received WPRT. A cohort of surgically-treated patients from the same multi-institutional database had a pathologic node positivity rate of 17%. Biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific mortality (PCSM) were compared between groups using Cox proportional hazards models with propensity score adjustment. Propensity scores were calculated as the conditional probability of receiving WPRT given age, tumor stage, GS, and initial PSA. Results The median follow-up was 5.6 years. The median doses were isoeffective to 81 Gy and 96 Gy in 1.8 Gy fractions in the EBRT and EBRT-BT groups, respectively. The median WPRT dose was isoeffective to 50.4 Gy in 1.8 Gy fractions. In the EBRT group 94% of patients receiving WPRT and 96% of patients not receiving WPRT received ADT (median duration 23 months), and in the EBRT-BT group, 80% of patients receiving WPRT received ADT, and 98% not receiving WPRT received ADT (median duration 12 months). WPRT did not significantly improve PCSM in the EBRT group (HR = 0.76, 95% CI 0.45-1.3, p = .3), though it trended towards improvement in the EBRT-BT group (HR 0.46, 0.19-1.11, p = .08). Similar results were seen in a competing risks regression model, treating other cause mortality as a competing risk. WPRT improved bRFS among patients treated with EBRT-BT (HR = 0.4, 95% CI 0.29-0.54, p < .001) but not in those treated with EBRT (HR 1.1, 95% CI 0.67-1.68, p = 0.8). There was borderline improvement in DMFS in the EBRT-BT group (HR 0.64, 95% CI .40-1.03, p = .065), but not the EBRT group (HR = 1.21, 95% CI 0.76-1.93, p= .4). Conclusion WPRT offered a trend towards improved DMFS and PCSM in this large cohort of patients with biopsy GS 9-10 PCa, but only in those treated with EBRT+BT. This trend did not reach statistical significance. WPRT did significantly improve bRFS, but again only in patients treated with EBRT+BT. These results are hypothesis-generating in suggesting that a long-term clinical benefit to WPRT, if present, might only be seen in the setting of extreme dose-escalation to the prostate itself.

5059 Background: The effect of dose-escalation with HDR-BT boost for high-risk PCa is not known. The objective is to compare 10-year PCa-specific mortality (PCSM) and overall mortality (OM) in non-metastatic patients treated with HDR-BT/EBRT (2004-2010) to EBRT alone (historical RCT, SPCG-7, 1996-2003). Methods: HDR-BT boosts (10 Gy x 2) were given 2 weeks apart followed by 50 Gy conformal EBRT (2 Gy x 25) to the prostate and seminal vesicles (assuming alpha/beta ratio of 3, EQD2 = 102 Gy). The HDR-BT/EBRT group (N:325) received Androgen Deprivation Therapy (ADT) for a total of 2 years. Patients in the control group (N:296) received 70 Gy (2Gy x 35) to the prostate and seminal vesicles with lifelong Anti-Androgen Treatment (AA). cT1-cT2 vs cT3 tumours and Gleason score 6-7 vs 8-10 were analysed. For each treatment group PCSM and OM were established by Kaplan-Meier (KM) analyses, and inter-treatment differences were tested by the logrank tests. Cox regression analysis evaluated the significance of available pre-treatment variables. Significance level p < 0.05. Results: In both groups the median age was 66 years. Median follow-up was 104 (range 13-120) and 120 (range 3-120) months for the HDR-BT/EBRT and EBRT groups respectively. KM plots revealed an 1.8% risk of PCSM in the HDR-BT/EBRT patient group and an 8.4% risk in the EBRT cohort (p = 0.001). For OM, the figures were 12.3% in the HDR-BT/EBRT group compared to 23.3% in the EBRT group (p = 0.014). In the Cox regression analysis, treatment (HR = 3.9, CI95% 1.8-8.3) and Gleason score (HR = 3.2, CI95% 1.8-5.9) were significantly associated with PCSM whilst T-stage, age and PSA levels were not. Treatment (HR = 1.7, CI95% = 1.1-2.6) was the only factor significantly associated with OM. Conclusions: In men with high-risk PCa dose-escalation with HDR-BT/EBRT compared to EBRT alone resulted in a significantly decreased risk of 10-year PCSM and OM despite shorter length of hormonal therapy. PCSM was significantly influenced by both Gleason score and type of treatment, whereas treatment remained the only significant covariate for OM.