Impact of Elapsed Treatment Time on Outcome of External-Beam Radiation Therapy for Localized Carcinoma of the Prostate

Abstract

The purpose of this study was to evaluate the impact of elapsed treatment time in external-beam radiation therapy for localized prostate carcinoma. 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 < or = 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. In patients with stage T1c, local failure ranged from 0% to 10% with doses < or = 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 < or = 70 Gy, overall pelvic failure rate was 4% (12/306) in those with an elapsed treatment time of < or = 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. 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.