Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: A randomized controlled trial

Context: Clinically localized prostate cancer is very prevalent among US men, but recurrence after treatment with conventional radiation therapy is common. Objective: To evaluate the hypothesis that increasing the radiation dose delivered to men with clinically localized prostate cancer improves disease outcome. Design, Setting, and Patients: Randomized controlled trial of 393 patients with stage T1b through T2b prostate cancer and prostate-specific antigen (PSA) levels less than 15 ng/mL randomized between January 1996 and December 1999 and treated at 2 US academic institutions. Median age was 67 years and median PSA level was 6.3 ng/mL. Median follow-up was 5.5 (range, 1.2-8.2) years. Intervention: Patients were randomized to receive external beam radiation to a total dose of either 70.2 Gy (conventional dose) or 79.2 Gy (high dose). This was delivered using a combination of conformal photon and proton beams. Main Outcome Measure: Increasing PSA level (ie, biochemical failure) 5 years after treatment. Results: The proportions of men free from biochemical failure at 5 years were 61.4% (95% confidence interval, 54.6%-68.3%) for conventional-dose and 80.4% (95% confidence interval, 74.7%-86.1%) for high-dose therapy (P<.001), a 49% reduction in the risk of failure. The advantage to high-dose therapy was observed in both the low-risk and the higher-risk subgroups (risk reduction, 51% [P<.001] and 44% [P=.03], respectively). There has been no significant difference in overall survival rates between the treatment groups. Only 1% of patients receiving conventional-dose and 2% receiving high-dose radiation experienced acute urinary or rectal morbidity of Radiation Therapy Oncology Group (RTOG) grade 3 or greater. So far, only 2% and 1%, respectively, have experienced late morbidity of RTOG grade 3 or greater. Conclusions: Men with clinically localized prostate cancer have a lower risk of biochemical failure if they receive high-dose rather than conventional-dose conformal radiation. This advantage was achieved without any associated increase in RTOG grade 3 acute or late urinary or rectal morbidity.