UROLOGICAL ONCOLOGY

Postoperative Radiotherapy After Radical Prostatectomy: A Randomised Controlled Trial (EORTC trial 22911)
Bolla M, van Poppel H, Collette L, van Cangh P, Vekemans K, Da Pozzo L, de Reijke TM, Verbaeys A, Bosset JF, van Velthoven R, Marechal JM, Scalliet P, Haustermans K, Pierart M; European Organization for Research and Treatment of Cancer
Department of Radiation Oncology, Centre Hospitalier Universitaire A Michallon, Grenoble, France
Lancet. 2005; 366 (9485): 572-8; Comment in: Lancet. 2005; 366 (9485): 524-5.

• 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.
  
  
• Editorial Comment
  The problem of positive surgical margins after radical prostatectomy is common. The question is the best adjuvant treatment in this scenario, immediate or deferred radiotherapy? This important paper gives a definite answer.
  Time to failure was significantly longer in the immediate radiotherapy group, with 21.4% of patients failing after 5 years in this group vs 44.2% in the deferred treatment group. Data on survival differences are not mature yet.
  Immediate adjuvant radiation should be considered in margin-positive patients after radical therapy.

Dr. Andreas Bohle
Professor of Urology
HELIOS Agnes Karll Hospital
Bad Schwartau, Germany