Systematic review and meta-analysis of trials evaluating the role of adjuvant radiation after radical prostatectomy for prostate cancer: Implications for early salvage.

introductionRecent reports suggest that early salvage radiation (esRT) is non-inferior to adjuvant radiation (aRT) for adverse pathological features at radical prostatectomy. However, aRT was accepted as a standard treatment primarily based on effects on biochemical progression-free survival (bPFS). In order to understand the merits of esRT, the objective was to reassess if aRT vs. observation is associated with improved overall survival (OS).

methodsA systematic review and meta-analysis of published randomized trials evaluating aRT was performed. The primary outcome was OS. Secondary outcomes were metastasis-free survival (MFS), loco-regional recurrence-free survival (RFS), bPFS, and adverse events. We performed a random-effects meta-analysis.

resultsFour randomized trials including 2068 patients with a median followup of 8.7-12.6 years were identified. While all trials reported a bPFS benefit, only one reported an OS benefit. Upon meta-analysis, no significant OS benefit was detected with aRT vs. observation (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.61-1.33), although consistent bPFS (HR 0.47, 95% CI 0.41-0.54) and local-RFS (HR 0.54, 95% CI 0.39-0.73) benefits were noted. There is an uncertain MFS benefit with aRT (HR 0.79, 95% CI 0.62-1.01), and the effect is largely driven by one trial with a notable risk of bias. There was also a risk of overtreatment, with 35-60% of patients being biochemical recurrence-free with observation alone. Adverse events risk was greater with aRT vs. observation.

conclusionsAlthough aRT vs. observation provides a bPFS benefit related to local control, there is no clear OS or MFS benefit, a greater risk of adverse events, and a risk of overtreatment. By extension, these data have implications for patient selection and counselling for esRT.