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PURPOSE It remains unknown whether or not short-term androgen deprivation (STAD) improves survival among men with intermediate-risk prostate cancer (IRPC) treated with dose-escalated radiotherapy (RT). METHODS The NRG Oncology/Radiation Therapy Oncology Group 0815 study randomly assigned 1,492 patients with stage T2b-T2c, Gleason score 7, or prostate-specific antigen (PSA) value >10 and ≤20 ng/mL to dose-escalated RT alone (arm 1) or with STAD (arm 2). STAD was 6 months of luteinizing hormone–releasing hormone agonist/antagonist therapy plus antiandrogen. RT modalities were external-beam RT alone to 79.2 Gy or external beam (45 Gy) with brachytherapy boost. The primary end point was overall survival (OS). Secondary end points included prostate cancer–specific mortality (PCSM), non-PCSM, distant metastases (DMs), PSA failure, and rates of salvage therapy. RESULTS Median follow-up was 6.3 years. Two hundred nineteen deaths occurred, 119 in arm 1 and 100 in arm 2. Five-year OS estimates were 90% versus 91%, respectively (hazard ratio [HR], 0.85; 95% CI, 0.65 to 1.11]; P = .22). STAD resulted in reduced PSA failure (HR, 0.52; P CONCLUSION STAD did not improve OS rates for men with IRPC treated with dose-escalated RT. Improvements in metastases rates, prostate cancer deaths, and PSA failures should be weighed against the risk of adverse events and the impact of STAD on quality of life.

258 Background: Radiation dose escalation with the addition of a brachytherapy boost (BT) to external beam radiation therapy (EBRT) may be associated with improved survival in certain men with Gleason grade 5 (GG5) prostate cancer (PCa). However, low PSA, high-grade PCa has much worse outcomes, is associated with neuroendocrine genomic features, and may be more resistant to androgen suppression. It is unclear whether the addition of a BT boost in men with this disease subgroup is associated with a survival benefit and is the subject of this analysis. Methods: Men diagnosed with node-negative, non-metastatic GG5 PCa and treated with (1) EBRT plus ADT or (2) EBRT plus BT plus ADT between 2004 and 2015 were identified in the National Cancer Database (NCDB). The EBRT cohort received conventionally fractionated ≥ 74 Gy or moderately hypofractionated (2.5-3.0 Gy x 20-28 fractions) EBRT. EBRT plus BT cohort received external beam doses of conventionally fractionated ≥45 Gy or moderately hypofractionated (2.5 Gy x 15 – 18 fractions) radiation, and either LDR or HDR BT. Men receiving chemotherapy, immunotherapy, or any form of surgery were excluded. Patients were stratified into two groups based on whether the presenting PSA was above or below the normal threshold (≤4 and > 4 ng/mL). OS was compared using the Kaplan-Meier and log-rank test. Multivariable analysis (MVA) using Cox proportional hazards regression modeling was performed, accounting for age, race, year of diagnosis, Charlson-Deyo comorbidity score, insurance status, treatment facility type, Gleason Score (9 versus 10), and clinical T-stage. Results: 8,260 men met study inclusion criteria of which 658 (8%) presented with PSA ≤4. 572 (87%) patients were treated with EBRT monotherapy and 86 (13%) patients were treated with EBRT + BT. 5-year OS for EBRT versus EBRT plus BT was 79.7 +/- 2.3% versus 86.9 +/- 5.0%, respectively (P = 0.49). On MVA analysis, EBRT plus BT was not associated with improved OS versus EBRT (adjusted HR 0.90, 95% CI 0.52-1.87; P = 0.62). In comparison, for men with PSA > 4 and GG5 disease [EBRT: 6,780 patients (89.2%) & EBRT plus BT: 822 patients (10.8%)], EBRT plus BT was associated with improved OS versus EBRT (adjusted HR 0.85, 95% CI 0.66-0.99; P = 0.044). Conclusions: Receipt of dose-escalated prostate radiation by means of a BT boost was not associated with improved survival in men with PSA ≤4 ng/mL and GG5 prostate cancer. By contrast, an association with improved survival was observed in men with GG5 disease and higher initial PSA. This low PSA, high-grade subgroup may represent a unique risk tier for which current treatment paradigms need further investigation, including study of escalated systemic therapy.

246 Background: SBRT and HDR brachytherapy have emerged as definitive salvage re-irradiation options for men with locally recurrent prostate cancer after prior radiation therapy (RT). Toxicity with re-irradiation remains a concern in this setting, particularly for salvage of periurethral recurrences. We calculated the normal tissue complication probability (NTCP) of urethral stricture following salvage re-irradiation (HDR and SBRT) after previous definitive RT (external beam or HDR) for periurethral recurrences. Methods: Two upfront definitive treatment plans were generated for 5 men with localized prostate cancer: External Beam RT (EBRT1) to a dose of 79.2 Gy in 1.8 Gy fractions and HDR monotherapy (HDR1), 13.5 Gy x 2 implants. Periurethral recurrences were virtually created on diagnostic MRI scans for each of the five men and defined as a recurrent dominant intraprostatic lesion (DIL). Three salvage RT plans were generated for each patient (constraints in Table): HDR salvage (10 Gy whole gland; 13.5 Gy to DIL; 2 implants), SBRTr with maximal rectal sparing (constraints designed for salvage following prior EBRT; 30 Gy in 5 fractions whole gland; 40 Gy in 5 fractions to DIL), and SBRTu with maximal urethral sparing (constraints designed for patients with prior HDR monotherapy; same Rx). DVH data was collected for each plan (previous RT and each salvage approach) and the equivalent uniform dose (EUD) was calculated. NTCP for the urethral stricture in the summed plans (prior definitive treatment + each salvage plan) was calculated by the Lyman-Kutcher-Burman model using the following parameters: (α/β = 5Gy; TD50= 116.7; m = 0.23; n = 0.3). Results: Prescription coverage of 90% of the DIL volume was achieved for each plan. The mean NTCP of urethral stricture for EBRT1 + HDR salvage was 55.2% (range, 52.2-59.1%) and for HDR1 + HDR salvage was 49.2% (42.9-57.5%). For EBRT1 + SBRTr and EBRT1 + SBRTu the NTCP for urethral stricture was 54.0% (50.4-61.0%) and 43.2% (39.4-48.4%), respectively. The NTCP of urethral stricture for HDR1 + SBRTr was 48.1% (41.0-57.2%) and for HDR1 + SBRTu was 37.6% (30.9-44.6%). Conclusions: In this modeling analysis of salvage RT for periurethral recurrences following previous RT (EBRT or HDR monotherapy), the NTCP for urethral stricture was numerically lowest for salvage SBRT using maximum urethral sparing dose constraints in comparison to salvage SBRT with maximum rectal sparing constraints or salvage HDR brachytherapy. This type of analysis lends insight into personalized treatment planning based on previous RT modality and previous dose to organs at risk. Expanded analysis is underway. [Table: see text]