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

Purpose: To study the effective doses of radiotherapy (RT) after prostatectomy in search for evidence of a doseresponse. Methods and Materials: 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. Results: 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 similar to 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. Conclusions: 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. (c) 2008 Elsevier Inc.