Risk-group dependence of dose-response for biopsy outcome after three-dimensional conformal radiation therapy of prostate cancer

Background and purpose: We fit phenomenological tumor control probability (TCP) models to biopsy outcome after three-dimensional conformal radiation therapy (3D-CRT) of prostate cancer patients to quantify the local dose-response of prostate cancer. Materials and methods: We analyzed the outcome after photon beam 3D-CRT of 103 patients with stage T1c-T3 prostate cancer treated at Memorial Sloan-Kettering Cancer Center (MSKCC) (prescribed target doses between 64.8 and 81 Gy) who had a prostate biopsy performed greater than or equal to2.5 years after end of treatment. A univariate logistic regression model based on D-mean (mean dose in the planning target volume of each patient) was fit to the whole data set and separately to subgroup, characterized by low and high values of tumor-related prognostic factors T-stage (<T2c vs. ≥T2c), Gleason score (≤6 vs. >6), and pre-treatment prostate-specific antigen (PSA) (less than or equal to10 ng/ml vs. > 10 ng/ml). In addition, we evaluated five different classifications of the patients into three risk groups, based on all possible combinations of two or three prognostic factors, and fit bivariate logistic regression models with D-mean and the risk group category to all patients. Dose-response curves were characterized by TCD50, the dose to control gamma(50)% of the tumors, and gamma(50), the normalized slope of the dose-response curve at TCD50. Results: D-mean correlates significantly with biopsy outcome in all patient subgroups and larger values of TCD50 are observed for patients with unfavorable compared to favorable prognostic factors. For example, TCD50 for high T-stage patients is 7 Gy higher than for low T-stage patients, For all evaluated risk group definitions, D-mean and the risk group category are independent predictors of biopsy outcome in bivariate analysis. The fit values of TCD50 show a clear separation of 9-10.6 Gy between low and high risk patients. The corresponding dose-response curves are steeper (gamma(50) = 3.4-5.2) than those obtained when all patients are analyzed together (gamma(50) = 2.9). Conclusions: Dose-response of prostate cancer, quantified by TCD50 and gamma(50), varies by prognostic subgroup. Our observations are consistent with the hypothesis that the shallow nature of clinically observed dose-response curves for local control result from a patient population that is a heterogeneous mixture of sub-populations with steeper dose-response curves and varying values of TCD50. Such results may eventually hell) to identify patients, based on their individual pro-treatment prognostic factors, that would benefit most from dose-escalation, and to guide dose prescription. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.