The benefit of adding androgen deprivation therapy (ADT) to dose- escalated radiation therapy (RT) for men with intermediate-risk prostate cancer is unclear, therefore, we assessed the impact of adding ADT to dose- escalated RT on PSA disease-free survival (bDFS).
Three groups of men treated with IMRT or 3D conformal RT from 1993-2008 for prostate cancer with doses ranging from 75.6-78 Gy were identified: (1) 327 intermediate-risk patients (NCCN classification) treated with RT alone, (2) 218 intermediate-risk patients treated with RT and <6 months of ADT, and (3) 274 low-risk patients treated with definitive RT. Median follow-up was 58 months. Recursive partitioning analysis using Gleason Score (GS), T-Stage, and pretreatment PSA was applied to the intermediate-risk patients treated with RT alone to identify prognostic groups based on risk of PSA recurrence (Phoenix definition). All intermediate-risk patients were then stratified by these prognostic subgroups. Intermediate-risk patients treated with RT alone were compared to intermediate-risk patients treated with RT and ADT and to low-risk patients treated with RT alone. Kaplan-Meier method was used to estimate the 5 year bDFS.
Based on recursive partitioning analysis of 5 year bDFS, intermediate-risk patients treated with RT alone were classified into 3 prognostic groups: (1) 188 favorable patients with T1b-T2b GS 6 or T1b-c GS 3+4; (2) 71 marginal patients with T2a-b GS 3+4; and (3) 68 unfavorable patients with T2c or GS 4+3 disease. Associated hazard ratios (HR) for recurrence were 1.0, 2.1, and 4.5, respectively. PSA was not found to be a major contributing factor in this analysis. When intermediate-risk patients treated with RT alone were compared to intermediate-risk patients treated with RT and ADT, the greatest benefit from ADT was seen for the unfavorable intermediate-risk patients (bDFS 74% vs. 94%; HR 0.234; p = .005). Favorable intermediate-risk patients had no significant benefit from the addition of ADT to RT (bDFS 94% vs. 95%; p = 0.85), and bDFS for favorable intermediate-risk patients treated with RT alone approached the bDFS for low-risk patients treated with RT alone (98%). In the marginal prognosis subgroup, 5 year bDFS was 91% without ADT and 100% with ADT, p = .07.
Patients with favorable intermediate- risk prostate cancer did not benefit from the addition of ADT to dose- escalated RT and their bDFS was nearly as good as patients with low-risk disease. However, in patients with GS 4+3 and higher volume disease, the addition of ADT to dose- escalated RT did improve bDFS. Since randomized trials addressing this issue in the high dose era are lacking, consideration should be given to a personalized approach, taking into account tumor characteristics and patient comorbidities.
Author Disclosure: K.O. Castle: None. K.E. Hoffman: None. L.B. Levy: None. A.K. Lee: None. S. Choi: None. Q.N. Nguyen: None. S.J. Frank: None. T. Pugh: None. S.E. McGuire: None. D.A. Kuban: F. Consultant/Advisory Board; Ferring Pharmaceuticals, Biotheranostics.
© 2011 Published by Elsevier Inc.