External beam radiotherapy dose response characteristics of 1127 men with prostate cancer treated in the PSA era

Purpose: To characterize the relationship of radiotherapy dose to prostate cancer patient outcome, with an emphasis on the influence of pretreatment p rognostic variables. Methods and Materials: The 1127 Stage T1-T4 prostate cancer patients examin ed were treated consecutively with definitive external beam radiotherapy at the University of Texas-M.D. Anderson Cancer Center from 1987 to 1997. All had a pretreatment prostate-specific antigen (PSA) level. Treatment failur e was defined as two consecutive PSA elevations on follow-up, There were 99 4 patients treated with a four-field box throughout to 60-70 Gy after a sma ll reduction at 46 Gy and 161 treated with a six-field conformal boost afte r 46 Gy to 74-78 Gy, No patient received neoadjuvant or adjuvant androgen a blation. Median follow-up was 51.8 months. Results: Patients were divided into three radiotherapy dose groups consisti ng of less than or equal to 67 Gy (n = 500), >67-77 Gy (n = 495), and >77 G y (n = 132), Relative to other prognostic factors, there were fewer patient s treated to the highest dose level with a pretreatment PSA (PSAB) less tha n or equal to 4 or >20 ng/ml, Stage T3/T4 disease, or a Gleason score of 2- 6, Actuarial 4-year freedom from biochemical failure (bNED) rates for the e ntire cohort were 54%, 71%, and 77% (p < 0.0001) for the low-, intermediate -, and high-dose groups, PSAB, palpable stage, and Gleason score were also highly significant. Tn Cox proportional hazards regression, dose (p < 0.000 1 as a continuous or categorical variable) was an independent predictor of bNED, as were the other prognostic factors, Pairwise univariate comparisons showed that an increase in dose from less than or equal to 67 Gy to >67-77 Gy was associated with improved bNED rates for all PSAB (less than or equa l to 10 and >10), stage (T1/T2 and T3/T4), and Gleason score (2-6 and 7-10) subgroups tested. In contrast, the only prognostic group that benefited fr om raising dose from >67-77 Gy to >77 Gy was patients with a PSAB >10 ng/ml ; although trends were noted for Stage T1/T2 and Gleason 2-6 patients. Pati ents with the combined features of a PSAB >10 ng/ml and Stage T1/T2 disease had 4-year bNED rates of 61% and 93% at the intermediate- and high-dose le vels. A strongly significant linear association between dose (60-78 Gy) and 4-year actuarial bNED was demonstrated for patients with these intermediat e-risk features. Conclusion: Prostate cancer dose response to external beam radiotherapy sho uld be considered in the context of pretreatment prognostic factors, Our da ta indicate that, for favorable patients with a PSAB of less than or equal to 10 ng/ml, intermediate doses of >67-77 Gy provide the same rate of contr ol as higher doses. However, longer follow-up may reveal a benefit to dose escalation >77 Gy, even in this favorable subset. Substantial and clinicall y relevant enhancements in bNED were seen at all dose levels for moderate-r isk patients, such as those having a PSAB >10 ng/ml and Stage T1/T2 disease . Sustained bNED was not realized for high-risk patients, even using 78 Gy; these patients may be best treated with higher doses, whole pelvic irradia tion, and/or androgen ablation plus radiation. (C) 2000 Elsevier Science In c.