In a systematic review and meta-analysis reported in The Lancet, Claire L. Vale, PhD, and colleagues found that immediate adjuvant radiotherapy did not improve event-free survival vs early salvage radiotherapy in men with intermediate-risk or high-risk localized or locally advanced prostate cancer undergoing radical prostatectomy.
The study used a prospective framework for adaptive meta-analysis that permitted a start of the review process while eligible trials comparing adjuvant vs salvage radiotherapy were ongoing, through collaboration with trialists. The primary outcome measure was event-free survival, defined as the time from random assignment until first evidence of either biochemical progression (prostate-specific antigen [PSA] ≥ 0.4 ng/mL and rising after completion of any postoperative radiotherapy), clinical or radiologic progression, initiation of a nontrial treatment, death from prostate cancer, or a PSA level ≥ 2.0 ng/mL at any time after random assignment.
“This collaborative and prospectively designed systematic review and meta-analysis suggests that adjuvant radiotherapy does not improve event-free survival in men with localized or locally advanced prostate cancer. Until data on long-term outcomes are available, early salvage treatment would seem the preferable treatment policy, as it offers the opportunity to spare many men radiotherapy and its associated side effects.”— Claire L. Vale, PhD, and colleagues
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Three eligible trials were identified—GETUG AFU-17, RAVES, and RADICALS-RT—with updated event-free survival results for 2,153 patients recruited between November 2007 and December 2016. Median follow-up ranged from 60 to 78 months, with a maximum follow-up of 132 months.
Overall, 1,075 patients were randomly assigned to receive adjuvant radiotherapy and 1,078 to a strategy of early salvage radiotherapy; among those in the salvage radiotherapy group, 421 (39.1%) had initiated treatment at the time of analysis. Overall, 77.6% of patients had a Gleason score of 7. Across the trials, early salvage radiotherapy was triggered at PSA levels of 0.2 ng/mL, 0.2 ng/mL and rising, and 0.1 ng/mL or three consecutive increases still below 0.1 ng/mL.
The 5-year rate of event-free survival was 89% in the adjuvant radiotherapy group vs 88% in the salvage radiotherapy group (hazard ratio [HR] = 0.95, 95% confidence interval [CI] = 0.75–1.21; P = .70).
Results were consistent across trials (heterogeneity P = .18, I² = 42%). Hazard ratios for adjuvant vs salvage radiotherapy were 1.10 (95% CI = 0.81–1.49) in the RADICALS-RT trial, 0.57 (95% CI = 0.30–1.08) in the GETUG AFU-17 trial, and 0.87 (95% CI = 0.51–1.48) in the RAVES trial.
Most event-free survival events were biochemical progression. At 5 years, the proportion of patients free of biochemical progression was 88% in RADICALS-RT, 94% in GETUG-AFU 17, and 87% in RAVES.
The investigators concluded, “This collaborative and prospectively designed systematic review and meta-analysis suggests that adjuvant radiotherapy does not improve event-free survival in men with localized or locally advanced prostate cancer. Until data on long-term outcomes are available, early salvage treatment would seem the preferable treatment policy, as it offers the opportunity to spare many men radiotherapy and its associated side effects.”
Dr. Vale, of MRC Clinical Trials Unit, University College Hospital, London, is the corresponding author for The Lancet article.
Disclosure: The study was funded by the UK Medical Research Council. For full disclosures of the study authors, visit thelancet.com.