Whole-Pelvic Versus Prostate-Only Radiation Therapy in Unfavorable Intermediate-Risk and High-Risk Prostate Cancer Treated with Androgen Deprivation Therapy and Brachytherapy Boost

Abstract

The ASCENDE-RT randomized controlled trial showed that brachytherapy boost significantly reduces biochemical recurrence in unfavorable intermediate-risk and high-risk prostate cancer treated with whole-pelvic radiation therapy (WPRT) and androgen deprivation therapy (ADT). However, previous level 1 data have not shown an oncologic benefit for WPRT compared to prostate-only radiation therapy (PORT) in patients who did not receive brachytherapy boost. Therefore, we examined the association between WPRT, compared to PORT, and overall survival in patients with unfavorable intermediate-risk or high-risk prostate cancer treated with brachytherapy boost and ADT. Using the National Cancer Database, we identified 7,292 men diagnosed with unfavorable intermediate-risk disease (Gleason 4+3 or ≥2 intermediate-risk factors [Gleason 3+4, prostate-specific antigen (PSA) 10-20 ng/mL, or cT2b-T2c stage]) or high-risk disease (Gleason 8-10, PSA >20 ng/mL, or cT3-T4 stage) from 2004 through 2014 who were treated with brachytherapy boost, ADT, and either WPRT or PORT to 39.6-50.4 Gy. Patients with nodal or metastatic disease were excluded. Risk of lymph node metastases was estimated using the Roach formula ([2/3] × PSA + 10 × [Gleason score - 6]). Cox proportional hazards regression was used to examine the association between WPRT, versus PORT, and overall survival. Median follow-up was 6.3 years. The study cohort consisted of 35.1% unfavorable intermediate-risk patients and 64.9% high-risk patients. Overall, 52.5% of patients received WPRT. On multivariable analysis, WPRT, compared to PORT, was not associated with a significant improvement in overall survival for the entire cohort (adjusted hazard ratio [AHR] 1.02, 95% confidence interval [CI] 0.91-1.14, P =0.702). This lack of overall survival benefit was observed for subgroups of unfavorable intermediate-risk patients (AHR 1.12, 95% CI 0.93-1.35, P =0.246), high-risk patients (AHR 0.98, 95% CI 0.85-1.12, P =0.726), and patients with >15% risk of lymph node metastases (AHR 1.00, 95% CI 0.89-1.13, P =0.985). These results suggest that patients with unfavorable intermediate-risk or high-risk prostate cancer treated with brachytherapy boost and ADT may not benefit from receiving WPRT. Providers should thoughtfully weigh the risks and benefits of WPRT compared to PORT when planning to treat unfavorable-risk patients with brachytherapy boost and ADT.