David Bryan, M.D. 's Urology Blog

Adjuvant (post operative) Radiotherapy for High-Risk Prostate Cancer

At median follow-up of 10.6 years, postoperative radiotherapy improved biochemical progression-free survival (PSA undetectable), but not clinical disease progression.

The goal of adjuvant radiotherapy after radical prostatectomy is to sterilize the prostatic bed and, in selected settings, regional nodes to decrease the potential for local recurrence and, ultimately, reduce the systemic spread of the disease and improve survival. Recent randomized trials have shown that in patients with T3 disease or positive surgical margins, postoperative radiotherapy to the surgical bed improves local control and biochemical (prostate-specific antigen) progression-free survival (PFS).

One of these trials, by the Southwest Oncology Group (SWOG), demonstrated that adjuvant radiotherapy versus observation significantly reduced risk for distant metastases and improved overall survival (J Urol 2009; 181:956). However, another one, by the European Organisation for Research and Treatment of Cancer (EORTC) did not show such an overall survival benefit. The EORTC study reported results after a median 5-year follow-up of 1005 patients (age, ≤75) with pathologic stage PT2-3,N0 and at least one of the following risk factors: positive surgical margins, capsular perforation, or seminal vesicle invasion (Lancet 2005; 366:572).

Now, after a median 10.6 years of follow-up, the EORTC investigators report that patients who received adjuvant radiotherapy versus observation continued to achieve improved biochemical PFS (the primary end point) with similar severe late toxicity. Patients who received radiotherapy also achieved improved local–regional control and were less likely to receive subsequent hormonal treatment. However, no intergroup differences were observed in either overall survival or distant metastases, and the initial observation of a significant improvement in clinical disease progression was not maintained. Patients with pT3 disease and positive surgical margins achieved the greatest benefit from adjuvant radiotherapy.

Comment: The discordant findings of the EORTC and SWOG studies on overall survival continue to be the subject of debate, and the larger clinical issue regarding the role of immediate adjuvant radiotherapy versus salvage radiotherapy was not addressed, though it is the subject of ongoing clinical trials. As noted by editorialists, the EORTC trial showed that adjuvant radiotherapy resulted in acceptable long-term morbidity and quality of life as well as reduced the use of subsequent androgen deprivation therapy (ADT) by half, although the timing and clinical setting in which ADT is administered remains controversial.

— Robert Dreicer, MD, MS, FACP

Published in Journal Watch Oncology and Hematology November 13, 2012

CITATION:

Bolla M et al. Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: Long-term results of a randomised controlled trial (EORTC trial 22911). Lancet 2012 Oct 19; [e-pub ahead of print]. [PubMed® abstract]