Preliminary results of a randomized radiotherapy dose-escalation study comparing 70 Gy with 78 Gy for prostate cancer

Purpose: To determine the effect of radiotherapy dose on prostate cancer patient outcome and biopsy positivity in a phase III trial. Patients and Methods: A total of 305 stage T1 through T3 patients were randomized to receive 70 Gy or 78 Gy of external-beam radiotherapy between 1993 and 1998. Of these, 301 were assessable; stratification was based on pretreatment prostate-specific antigen level (PSA). Dose was prescribed to the isocenter at 2 Gy per fraction. All patients underwent planning pelvic computed tomography scan to confirm prostate position. Treatment failure was defined as an increasing PSA on three consecutive follow-up visits or the initiation of salvage treatment. Median follow-up was 40 months. Results: One hundred fifty patients were randomized to the 70-Gy arm and 151 to the 78-Gy arm. The difference in freedom from biochemical and/or disease failure (FFF) rates of 69% and 79% for the 70-Gy and 78-Gy groups, respectively, at 5 years was marginally significant (log-rank P = .058). Multiple-covariate Cox proportional hazards regression showed that the study randomization was an independent correlate of FFF, along with pretreatment PSA, Gleason score, and stage. The patients who benefited most from the 8-Gy dose escalation were those with a pretreatment PSA of more than 10 ng/ml; 5-year FFF rates were 48% and 75% (P = .011) for the 70-Gy and 78-Gy arms, respectively. There was no difference between the arms (~80% 5-year FFF) when the pretreatment PSA was ≤ 10 ng/mL. Conclusion: A modest dose increase of 8 Gy using conformal radiotherapy resulted in a substantial improvement in prostate cancer FFF rates for patients with a pretreatment PSA of more than 10 ng/mL. These findings document that local persistence of prostate cancer in intermediate- to high-risk patients is a major problem when doses of 70 Gy or less are used. (C) 2000 by American Society of Clinical Oncology.