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A Randomized Controlled Trial

Anthony L. Zietman, MD; Michelle L. DeSilvio, PhD; Jerry D. Slater, MD; Carl J. Rossi, Jr, MD; Daniel W. Miller, PhD; Judith A. Adams, MS; William U. Shipley, MD

JAMA. 2005;294:1233-1239.

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.

Author Affiliations: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston (Drs Zietman and Shipley and Ms Adams); Loma Linda University Medical Center, Loma Linda, Calif (Drs Slater, Rossi, and Miller); and American College of Radiology and Radiation Therapy Oncology Group, Philadelphia, Pa (Dr DeSilvio).

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