Radiotherapy after prostatectomy: is the evidence for dose escalation out there?

Abstract

To study the effective doses of radiotherapy (RT) after prostatectomy in search for evidence of a dose-response. Original and available data from published studies of adjuvant and salvage RT after prostatectomy were analyzed in the context of biochemical tumor control probability (TCP) dose-response curves. Comparisons were made with dose-escalation studies of radical RT for localized disease. Arguments based on a microscopic vs. macroscopic disease dose-response relationships were used to interpret the clinical data. The tumor control rates after salvage RT were consistent with the TCP dose-response curve of radical RT, suggesting the presence of macroscopic-equivalent disease among salvage patients. For radical RT, the dose to achieve 50% biochemical tumor control was 65.9 Gy (95% confidence interval [CI], 64.8-66.8) and the Slope(50) was 2.6%/Gy (95% CI, 2.3-3.0). For salvage RT, the corresponding values were 66.8 Gy (95% CI, 65.1-68.4) and 3.8%/Gy (95% CI, 2.5-7.6). For a comparable TCP, the dose for adjuvant RT was approximately 6 Gy lower, consistent with one-tenth the burden of local disease. The present doses for adjuvant or salvage RT in the range of 60-70 Gy appear to be still on the steep part of the TCP dose-response curve. The effective doses and dose-response relation observed with RT after prostatectomy are consistent with the presence of macroscopic-equivalent disease for salvage patients and about a tenth of the residual disease for adjuvant patients. Greater doses would potentially achieve significantly greater disease-free control rates. A randomized trial with 250 patients comparing 64 vs. 70 Gy for salvage RT or 60 vs. 66 Gy for adjuvant RT would be capable of addressing this issue.