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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 To identify differences in acute urinary and sexual toxicity between a 6-fraction and 2-fraction high-dose-rate brachytherapy monotherapy regimen and correlate dosimetric constraints to short-term toxicity. Methods A single institution retrospective study of 116 men with prostate cancer treated with HDR monotherapy from 2010 to 2015 was conducted. Eighty-one men had 7.25 Gy × 6-fractions and 35 men had 13.5 Gy × 2-fractions. Patients had two CT-planned implants spaced 1–2 weeks apart. Patient baseline characteristics, International Prostate Symptom Scores (IPSS) and Sexual Health Inventory for Men (SHIM) scores were collected pre-treatment and 3, 6 and 12 months post-implantation. Mixed effect modelling was undertaken to compare baseline, 1–6 month and 7–12 month scores between groups. Poisson regression analysis was performed to correlate dosimetric constraints with acute toxicity. Results There was no difference between baseline and post-implantation IPSS scores between 6-fraction and 2-fraction groups. SHIM scores for men treated with 6-fractions had a steeper decline at 1–6 months, but resolved at 7–12 months. Pre-treatment alpha-blocker use correlated with worse short-term acute urinary toxicity. Worsened SHIM score correlated with increasing age, diabetes mellitus and androgen-deprivation therapy. In a dosimetric analysis of outcomes, prostate V150 dose and bladder wall (D01.cc, D1cc, D2cc) dose correlated with increased IPSS score. Conclusion No increased acute genitourinary or sexual dysfunction has been observed in men when transitioning from 6-fraction to 2-fraction HDR monotherapy. A dosimetric correlation was found between the V150 and bladder wall doses for acute urinary toxicity. Future research should continue to standardize and validate dose constraints for prostate HDR monotherapy patients.

Purpose/Objective(s): To compare the outcomes of a modern cohort of patients with Gleason Score (GS) 9-10 prostate adenocarcinoma (PCa) following treatment with external beam radiotherapy (EBRT), extremely dose-escalated radiotherapy (exemplified by EBRT with a brachytherapy boost [EBRT+BT]), and radical prostatectomy (RP). Materials/Methods: One thousand four hundred three patients with biopsy GS 9-10 PCa who received definitive treatment between 2000 and 2013 were included (506 treated with EBRT, 392 with EBRT+BT, and 505 with RP). Distant metastasis-free survival (DMFS) and prostate cancer-specific mortality (PCSM) were compared across the three cohorts with four cause-specific Cox regression models: (a) unadjusted, (b) covariate-adjusted for age, ln(iPSA), cT stage, and GS, (c) propensity score adjusted for the same covariates, and (d) in a doubly robust analysis (i.e., propensity score and covariate adjusted). Four analogous Fine and Gray competing risk models were developed to compare cumulative PCSM incidence. Results: The median follow-up period was 5.1 years (5.1, 6.4, and 4.3 years in the EBRT, EBRT + BT, and RP cohorts, respectively). The median doses among EBRT and EBRT+BT patients were isoeffective to 81 Gy and 96 Gy in 1.8 Gy fractions, respectively. Over 90% of patients treated with EBRT or EBRT+BT received ADT (median durations of 23 months and 12 months, respectively). Nearly 40% of RP patients received postoperative RT; 78% of postoperative RT was delivered in the salvage setting. PCSM was significantly lower among EBRT+BT patients than among either EBRT or RP patients in all cause-specific hazard models and Fine and Gray competing risk models, including unadjusted models (P

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.

Purpose: To determine predictors of distant metastases (DM) in prostate cancer patients treated with high dose rate brachytherapy boost (HDR-B) and external beam radiation therapy (EBRT). Material and methods: From 1991 to 2002, 768 men with localized prostate cancer were treated with HDR-B and EBRT. The mean EBRT dose was 37.5 Gy (range: 30.6-45 Gy), and the HDR-B was 22 or 24 Gy delivered in 4 fractions. Univariate and multivariate analyses using a Cox proportional hazards model including age at diagnosis, T stage, Gleason score (GS), pretreatment PSA, biologically equivalent dose (BED), and use of androgen deprivation therapy (ADT) was used to determine predictors of developing distant metastases. Results: The median follow-up time for the entire patient population was 4.2 years (range: 1-11.2 years). Distant metastases were identified in 22/768 (3%) of patients at amedian of 4.1 years. PSA failure according to the Phoenix definition developed in 3%, 5%, and 14% of men with low, intermediate, and high risk disease with amedian time to failure of 3.8 years. Prostate cancer specific mortality was observed in 2% of cases. T stage, GS, and use of ADT were significantly associated with developing DM on univariate analysis. GS, and use of ADT were the only factors significantly associated with developing DM on multivariate analysis (p < 0.01). Patients who received ADT had significantly higher risk features suggesting patient selection bias for higher DM in this group of patients rather than a negative interaction between HDR-B and EBRT. Conclusions: In men treated with HDR-B and EBRT, GS is a significant factor on multivariate analysis for developing distant metastasis.

Purpose/Objective(s): To compare outcomes of patients with Gleason score (GS) 9-10 prostate adenocarcinoma (CaP) following external beam radiation therapy (EBRT), extremely dose-escalated radiation therapy (as exemplified by EBRT with a brachytherapy boost [EBRT+BT]), and radical prostatectomy (RP).

Table 1. Patient Characteristics (N=40) Median Follow-up (range in months) 35 (7-120) Median Age (range) 62 (38-79) Surgical Staging (# of pts) 39 Histology (# of pts) Endometrioid Adenocarcinoma 13 (32.5%) Papillary Serous 15 (37.5%) Clear Cell 11 (27.5%) Undifferentiated 1 (2.5%) Adjuvant Treatment (# of pts) Combined Chemotherapy and Radiation 23 EBRT+ VC 11 (3 extended field) EBRT only 8 (4 extended field) VC only 3 Chemotherapy or Radiation Alone (# of pts) 17 Chemotherapy alone (# of pts) 9 Radiation alone (# of pts) 8 EBRT+ VC 3 EBRT only 4 (2 extended field) VC only 1 Materials/Methods The optimal management of high-risk endometrial cancer has yet to be determined. A retrospective review was undertaken to determine whether adjuvant therapy with combined chemotherapy and radiation (CRT) versus either chemotherapy or radiation therapy alone (C/RT) impacts clinical outcomes. Figure 1 Local Failure (LF)