High-dose radiotherapy with or without androgen-deprivation therapy for intermediate-risk prostate cancer: Cancer control and toxicity.

Abstract

67 Background: Randomized studies show an improvement in biochemical failure-free survival (BFFS) and overall survival (OS) with the addition of androgen therapy (ADT) to external-beam radiotherapy (EBRT) for high-risk prostate cancer (PC). However, the role of ADT in intermediate risk PC in the current dose-escalation era remains poorly defined, as studies evaluating ADT in this group have included high-risk patients or did not use dose-escalation. Our goal was to evaluate the impact of ADT on cancer control and toxicity in intermediate-risk PC. Methods: From a multi-institutional IRB-approved database of 850 pts, we identified 251 intermediate risk PC patients (defined as ≥ T2b or PSA > 10 or Gleason score [GS] of 7, with none of the following: ≥ T3, PSA > 20, GS ≥ 8, positive nodes, distant metastases) treated with EBRT to a dose of ≥70 Gy (no brachytherapy or prostatectomy). Eighty-seven men received ADT; 164 did not. BFFS (Phoenix definition) and OS survival curves for ADT vs no-ADT arms were compared with the log rank test. Univariate and multivariate analyses of major demographic, disease and treatment factors were performed, as were chi-square analyses of genitourinary (GU) and gastrointestinal (GI) toxicity. Results: Median follow up was 47 mo. Mean dose [ADT vs no-ADT] was 76.8 Gy vs 76.2 Gy (p=0.41; range: 70.0-81.0 Gy). The ADT group had a higher mean PSA (12.0 vs 8.9, p<0.001), proportion of ≥ T2b (22 vs 11%, p<0.01) and proportion of pelvic XRT use (49 vs 22%, p<0.001) than the no-ADT group, but the groups were well-balanced by age, race, GS, EBRT dose and intensity-modulated radiotherapy (IMRT) use. For ADT vs no-ADT, 5-yr BFFS was 80% vs 76% (p=0.17) and 5-yr OS was 84% vs 76% (p=0.82). On multivariate analysis, only ADT (p=0.006) and GS (p=0.006) were significantly associated with BFFS, and only PSA (p=0.028) and IMRT use (p=0.011) reached significance for OS. There were no significant differences in acute or late GU or GI toxicity. Conclusions: While RTOG 0815 is exploring this study question in a randomized setting, our study suggests that the addition of ADT to dose-escalated EBRT may improve BFFS, but without a demonstrated OS benefit, and is not associated with additional EBRT-related GI or GU toxicity. No significant financial relationships to disclose.