LAUSR

Background: In prior retrospective studies, we assessed a number of prostate tumor tissue biomarkers that were associated independently with the clinical outcome of men treated with radiotherapy (RT) ± androgen deprivation therapy (ADT). In this report, the associations of selected biomarkers with biochemical or clinical disease failure (BCDF) were prospectively evaluated in men with T1‐T3 prostate cancer on a randomized hypofractionation trial. Methods: Biomarkers were analyzed in 263 of 303 men randomly assigned to standard vs moderate hypofractionation. Median follow‐up was 65.9 months. Archival tissue was analyzed for Ki‐67 (n = 231), MDM2 (n = 209), p16 (n = 195), Cox‐2 (n = 126), p53 (n = 206), bcl2 (n = 223), bax (n = 210), and PKA (n = 160). The base model for multivariable Fine‐Gray regression analysis included treatment assignment and risk groups. All statistical tests were two‐sided. Results: Each biomarker was tested one at a time relative to the base model and selected for inclusion in multivariable analysis. Ki‐67 (hazard ratio [HR] = 2.31, 95% confidence interval [CI] = 1.19 to 4.48, P = .01) and bcl2&bax (HR = 2.19, 95% CI = 1.08 to 4.46, P = .03) were statistically significantly related to higher BCDF and were independently statistically significant when considered jointly (Ki‐67: HR = 2.26, 95% CI = 1.12 to 4.58, P = .02; bcl2&bax: HR = 2.14, 95% CI = 1.03 to 4.41, P = .04). At 2.5 years postradiotherapy, the C‐index of Ki‐67 was 73.2%, while for the base model was only 46.2%; Ki‐67 was the most statistically significant when tested without bcl2&bax. Conclusions: In this prospective multiple biomarker analysis in men with prostate cancer treated with RT±ADT, both Ki‐67 and bcl2&bax were independently related to early BCDF; however, Ki‐67 alone is indicated to be the most clinically meaningful by C‐index analysis and is universally available.