The Lancet, Volume 380, Issue 9858, Pages 2018 - 2027, 8 December 2012

Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: long-term results of a randomised controlled trial (EORTC trial 22911)

Prof Michel Bolla MD , Prof Hein van Poppel MD, Prof Bertrand Tombal MD, Kris Vekemans MD, Luigi Da Pozzo MD, Theo M de Reijke PhD , Antony Verbaeys MD, Prof Jean-François Bosset MD, Prof Roland van Velthoven MD, Prof Marc Colombel MD, Cees van de Beek MD, Paul Verhagen PhD, Alphonsus van den Bergh PhD, Cora Sternberg MD, Prof Thomas Gasser MD, Geertjan van Tienhoven MD, Prof Pierre Scalliet MD, Prof Karin Haustermans MD, Laurence Collette PhD

Summary

Background

We report the long-term results of a trial of immediate postoperative irradiation versus a wait-and-see policy in patients with prostate cancer extending beyond the prostate, to confirm whether previously reported progression-free survival was sustained.

Methods

This randomised, phase 3, controlled trial recruited patients aged 75 years or younger with untreated cT0—3 prostate cancer (WHO performance status 0 or 1) from 37 institutions across Europe. Eligible patients were randomly assigned centrally (1:1) to postoperative irradiation (60 Gy of conventional irradiation to the surgical bed for 6 weeks) or to a wait-and-see policy until biochemical progression (increase in prostate-specific antigen >0·2 μg/L confirmed twice at least 2 weeks apart). We analysed the primary endpoint, biochemical progression-free survival, by intention to treat (two-sided test for difference at α=0.05, adjusted for one interim analysis) and did exploratory analyses of heterogeneity of effect. This trial is registered with ClinicalTrials.gov, number NCT00002511.

Findings

1005 patients were randomly assigned to a wait-and-see policy (n=503) or postoperative irradiation (n=502) and were followed up for a median of 10·6 years (range 2 months to 16·6 years). Postoperative irradiation significantly improved biochemical progression-free survival compared with the wait-and-see policy (198 [39·4%] of 502 patients in postoperative irradiation group vs 311 [61·8%] of 503 patients in wait-and-see group had biochemical or clinical progression or died; HR 0·49 [95% CI 0·41—0·59]; p<0·0001). Late adverse effects (any type of any grade) were more frequent in the postoperative irradiation group than in the wait-and-see group (10 year cumulative incidence 70·8% [66·6—75·0] vs 59·7% [55·3—64·1]; p=0.001).

Interpretation

Results at median follow-up of 10·6 years show that conventional postoperative irradiation significantly improves biochemical progression-free survival and local control compared with a wait-and-see policy, supporting results at 5 year follow-up; however, improvements in clinical progression-free survival were not maintained. Exploratory analyses suggest that postoperative irradiation might improve clinical progression-free survival in patients younger than 70 years and in those with positive surgical margins, but could have a detrimental effect in patients aged 70 years or older