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

Abstract

Introduction: Recent 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).

Methods: A 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.

Results: Four 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.

Conclusions: Although 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.

Conflict of interest statement

Competing interests: The authors report no competing personal or financial interests related to this work.

Figures

Fig. 1

PRISMA diagram.

Fig. 2

Summary of studies evaluating the association between adjuvant radiotherapy and oncologic and survival outcomes in patients with adverse features after prostatectomy. (A) Overall survival. (B) Metastasis-free survival. (C) Biochemical progression-free survival. (D) Loco-regional recurrence-free survival. Note that ARO-96-02 reported on metastasis-free and overall survival but a hazard ratio was not reported and, therefore, this trial could not contribute to the meta-analysis of these outcomes. CI: confidence interval; IV: inverse variance; RT: radiation therapy.