Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911)

Background: Local failure after prostatectomy can arise in patients with cancer extending beyond the capsule. We did a randomised controlled trial to compare radical prostatectomy followed by immediate external irradiation with prostatectomy alone for patients with positive surgical margin or pT3 prostate cancer. Methods: After undergoing radical retropubic prostatectomy, 503 patients were randomly assigned to a wait-and-see policy, and 502 to immediate postoperative radiotherapy (60 Gy conventional irradiation delivered over 6 weeks). Eligible patients had pN0M0 tumours and one or more pathological risk factors: capsule perforation, positive surgical margins, invasion of seminal vesicles. Our revised primary endpoint was biochemical progression-free survival. Analysis was by intention to treat. Findings: The median age was 65 years (IQR 61-69). After a median follow-up of 5 years, biochemical progression-free survival was significantly improved in the irradiated group (74·0%, 98% CI 68·7-79·3 vs 52·6%, 46·6-58·5; p<0·0001). Clinical progression-free survival was also significantly improved (p=0·0009). The cumulative rate of locoregional failure was significantly lower in the irradiated group (p<0·0001). Grade 2 or 3 late effects were significantly more frequent in the postoperative irradiation group (p=0·0005), but severe toxic toxicity (grade 3 or higher) were rare, with a 5-year rate of 2·6% in the wait-and-see group and 4·2% in the postoperative irradiation group (p=0·0726). Interpretation: Immediate external irradiation after radical prostatectomy improves biochemical progression-free survival and local control in patients with positive surgical margins or pT3 prostate cancer who are at high risk of progression. Further follow-up is needed to assess the effect on overall survival