Can EBRT Dose-Escalation Above 80 Gy Yield Comparable Survival Rates Relative to EBRT Plus Brachytherapy Boost in Men With Unfavorable Intermediate-Risk Prostate Cancer?

Abstract

PURPOSE/OBJECTIVE(S)\nCurrent recommendations regarding radiotherapy treatment for unfavorable intermediate-risk prostate cancer (UIR-PCa) include external beam radiotherapy (EBRT) ± brachytherapy boost (BT) ± androgen deprivation therapy (ADT). Dose-escalated EBRT ± ADT is associated with excellent long-term outcomes, but ERBT+BT ± ADT can achieve higher dose escalation beyond what can be achieved with EBRT alone. Prior studies have shown improved biochemical control and reduced distant metastasis with EBRT+BT vs. EBRT in men with intermediate-risk disease, but it is unclear if this translates into a survival benefit.\n\n\nMATERIALS/METHODS\nMen with UIR-PCa diagnosed between 2004 and 2015 and treated with EBRT ± ADT or EBRT+BT ± ADT were identified in the National Cancer Database (NCDB). EBRT was delivered with conventional fractionation (≥ 72 Gy in 1.8-2.0 Gy per fraction), while EBRT+BT was defined as patients receiving EBRT to a total dose of 40-50.4 Gy plus high-dose rate or low-dose rate brachytherapy. Patients with a Charlson-Deyo comorbidity index (CDCI) score > 1, who received systemic therapy other than ADT, or missing key information were excluded. Propensity-weighted multivariable analysis (MVA) using Cox regression modeling was used to compare overall survival (OS) hazard ratios. Covariables included age, race, ethnicity, year of diagnosis, CDCI score, insurance status, educational and socioeconomic metrics, treatment at an academic center, PSA at diagnosis, Gleason score, clinical T-stage, and receipt of ADT.\n\n\nRESULTS\nThe study cohort included 32,246 unfavorable intermediate-risk prostate cancer patients treated with: (i) EBRT (n\u202f=\u202f13,265), (ii) EBRT+ADT (n\u202f=\u202f13,123), (iii) EBRT+BT (n\u202f=\u202f3,440), or (iv) EBRT+BT+ADT (n\u202f=\u202f2,418). Cumulative doses of EBRT ± ADT are summarized in Table 1. The average time to follow-up was 62 months (standard deviation ± 39 months). Propensity-weighted MVA showed that EBRT+BT ± ADT was associated with improved OS relative to increasing doses of EBRT ± ADT. However, the OS benefit associated with EBRT+BT ± ADT diminished as the cumulative dose of radiation in the EBRT ± ADT cohort increased (Table 1).\n\n\nCONCLUSION\nThe addition of brachytherapy to EBRT correlated with reduced mortality in men with UIR prostate cancer, including patients treated with EBRT ± ADT to ≥80 Gy. The relative OS benefit associated with EBRT+BT declined as the radiation dose increased in the EBRT ± ADT cohort.