What Dose of External-Beam Radiation is High Enough for Prostate Cancer?

Purpose: To quantify the radiotherapy dose-response of prostate cancer, adjusted for prognostic factors in a mature cohort of men treated relatively uniformly at a single institution. Patients and Methods: The study cohort consisted of 1,530 men treated with three-dimensional conformal external-beam radiotherapy between 1989 and 2002. Patients were divided into four isocenter dose groups: <70 Gy (n = 43), 70-74.9 Gy (n = 552), 75-79.9 Gy (n = 568), and ≥80 Gy (n = 367). The primary endpoints were freedom from biochemical failure (FFBF), defined by American Society for Therapeutic Radiology and Oncology (ASTRO) and Phoenix (nadir + 2.0 ng/mL) criteria, and freedom from distant metastases (FFDM). Multivariate analyses were performed and adjusted Kaplan-Meier estimates were calculated. Logit regression dose-response functions were determined at 5 and 8 years for FFBF and at 5 and 10 years for FFDM. Results: Radiotherapy dose was significant in multivariate analyses for FFBF (ASTRO and Phoenix) and FFDM. Adjusted 5-year estimates of ASTRO FFBF for the four dose groups were 60%, 68%, 76%, and 84%. Adjusted 5-year Phoenix FFBFs for the four dose groups were 70%, 81%, 83%, and 89%. Adjusted 5-year and 10-year estimates of FFDM for the four dose groups were 96% and 93%, 97% and 93%, 99% and 95%, and 98% and 96%. Dose-response functions showed an increasing benefit for doses ≥80 Gy. Conclusions: Doses of ≥80 Gy are recommended for most men with prostate cancer. The ASTRO definition of biochemical failure does not accurately estimate the effects of radiotherapy at 5 years because of backdating, compared to the Phoenix definition, which is less sensitive to follow-up and more reproducible over time.