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Despite extensive application of prostate cancer screening and improvements in surgical techniques, 30% to 35% of patients who undergo radical prostatectomy ultimately will experience biochemical recurrence (detectable rising prostate-specific antigen [PSA] levels). Randomized trials of adjuvant radiotherapy have provided evidence that selected patients benefit (i.e., have lower biochemical recurrence rates). In 1992, the European Organisation for Research and Treatment of Cancer (EORTC) launched a phase III trial to evaluate the role of adjuvant radiotherapy in men with pT3N0M0 disease and at least one risk factor for progression (positive surgical margins, extraprostatic extension of tumor, or invasion of seminal vesicles): 1005 men were randomized to either postoperative observation or radiotherapy (60 Gy). Patients who were randomized to receive radiotherapy were treated within 16 weeks after surgery, regardless of their postoperative PSA levels. In the initial report on this study, the investigators suggested that adjuvant radiotherapy benefited all patients with adverse risk factors (Eur J Cancer 2005; 41:2662); however, the report did not contain either Gleason scores or data from subsequent reference pathology reviews.
Central pathology reviews of 566 prostatectomy specimens now have been completed; 322 were found to have positive surgical margins. The investigators assessed the interactions between five risk factors (positive surgical margin, extraprostatic extension, seminal vesicle invasion, high Gleason score, and high postoperative PSA level) and radiotherapy in terms of progression-free survival. They found no interaction of radiotherapy with postoperative PSA levels, Gleason scores, or seminal vesicle invasion. Radiotherapy was of borderline benefit in patients without extraprostatic extension overall, but this effect was eliminated when only patients with PSA values >0.2 ng/mL were considered. Margin status, as assessed by central pathology review, was the strongest predictor of prolonged progression-free survival with radiotherapy. The authors noted that three patients with positive margins would have to receive adjuvant radiotherapy to prevent one biochemical recurrence.
Van der Kwast TH et al. Identification of patients with prostate cancer who benefit from immediate postoperative radiotherapy: EORTC 22911. J Clin Oncol 2007 Sep 20; 25:4178.
Comment
Both prostate cancer screening and improved public awareness have lowered the number of patients who present initially with large bulky tumors; however, a subset of patients always will present with adverse risk factors. Randomized studies from both the EORTC and Southwest Oncology Group (JAMA 2006; 296:2329) have demonstrated a benefit for adjuvant radiotherapy in terms of rising PSA and disease recurrence, without affecting metastases-free or overall survival. The decision process is complicated, given prostate disease heterogeneity — not all patients with adverse risk factors will experience rising PSA levels, and some patients will benefit from delayed (i.e., salvage) radiotherapy. This update provides a framework for this discussion for patients with positive surgical margins.