Impact of elapsed treatment time on outcome of external-beam radiation therapy for localized carcinoma of the prostate

PURPOSE: The purpose of this study was to evaluate the impact of elapsed treatment time in external-beam radiation therapy for localized prostate carcinoma. MATERIALS AND METHODS: The medical records of 1083 patients with localized prostate carcinoma treated between 1970 and December 1999 with external irradiation alone were reviewed. Median follow-up was 6 years (range, 4-24 years). Since 1987, prostate-specific antigen levels were obtained in 687 patients before the initiation of radiation therapy, and all patients seen in follow-up had prostate-specific antigen determinations. There were 344 patients with T1c, 496 with T2, and 243 with T3 tumors. The elapsed treatment time was divided into ≤ 7, 7.1-9, or > 9 weeks. Local tumor control was determined by rectal examination and cause-specific survival or prostate-specific antigen failure according to American Society of Therapeutic Radiology and Oncology consensus criteria. Because of dose-escalation studies, tumor dose levels ranged from 66-73.8 Gy, given in 1.8- to 2-Gy fractions. RESULTS: In patients with stage T1c, local failure ranged from 0% to 10% with doses ≤ 72 Gy with; elapsed treatment time had no impact. No pelvic failures were detected in 88 patients receiving doses > 72 Gy. In patients with T2 who received ≤ 70 Gy, overall pelvic failure rate was 4% (12/306) in those with an elapsed treatment time of ≤ 9 weeks, in contrast to 27% (12/44) for those with an elapsed treatment time > 9 weeks; at 10 years, patients with T2 tumors treated in > 9 weeks had a higher actuarial pelvic failure rate (35%), in contrast to 5% to 18% with shorter treatment times. For patients with T2 tumors who received 70-72 Gy, pelvic failure rate ranged from 0% to 32%, and there were no failures in 37 patients treated to higher doses. In patients with prostate-specific antigen values whose tumors were stage T1c, the chemical failure rate was 41% (60/147) with a tumor dose < 70 Gy, compared with 17% (4/24) in those who received higher doses. In patients with stage 2 disease who were treated with < 70 Gy, the chemical failure rate was 31%, and the rate was 12%-18% in those who received higher doses. In stage T3, the clinical pelvic failure rate ranged from 25% to 32% in the three elapsed time groups, and the chemical failure rate ranged from 48% to 69%, and there was no significant correlation with elapsed time or total irradiation dose. Cause-specific survival without chemical failure in patients with stage T1c disease at 10 years was 85%-90% in the three elapsed treatment time groups. In patients with stage T2 disease, the corresponding values were 80% and 90% for elapsed treatment times < 9 weeks, in contrast to 65% for patients treated > 9 weeks. In patients with stage T3 disease, cause-specific survival was about 60% in all elapsed treatment groups. There was no significant correlation of elapsed treatment time with urinary or rectal morbidity. CONCLUSIONS: Patients treated with radiation therapy for stage T2 localized prostate carcinoma showed a greater incidence of pelvic and chemical failures and a lower cause-specific survival when elapsed treatment time was > 9 weeks in comparison with the failure and survival rates occurring with shorter times. Higher doses of irradiation (> 72 Gy) eliminate the influence of prolongation of treatment time on outcome.