Prostate HDR Monotherapy: the dangers of early reporting and misuse of the alpha/beta ratio
Well fractionated HDR brachytherapy as monotherapy is a safe and effective treatment for many men with prostate cancer, but can be logistically challenging and resource intensive. The apparent low alpha/beta ratio of prostate cancer has given radiobiological rationale to explore two and even single fraction regimens. Early outcome reports of single 19 Gy were very encouraging. We recruited 170 patients with low and intermediate risk disease to a randomized trial of 19 Gy x 1 or 13.5 Gy x 2. With a median follow-up of 5 years, those randomized to the 2-fraction arm continue to do well with a median 5-year PSA of 0.16 ng/ml, a biochemical disease-free survival of 95%, and a 3% cumulative incidence of local failure. Those randomized to the single fraction arm have done much worse, with a median 5-year PSA of 0.65 ng/ml, biochemical disease-free survival of 73% and a cumulative incidence of local failure of 29%. A subsequent phase II trial delivering 19 Gy to the whole prostate with MRI-directed boost of 27 Gy to the dominant nodule failed to improve results, with a local failure rate of 32% at 4 years. Single fraction HDR monotherapy should not be used, early reporting of clinical outcomes should be discouraged, and simple linear-quadratic calculations grossly overestimate the biological efficacy of single fraction protocols.
Odette Cancer Centre Sunnybrook Health Sciences Centre Canada