Prospective Validation of Diagnostic Tumor Biomarkers in Men Treated With Radiotherapy for Prostate Cancer JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE Pollack, A., Kwon, D., Walker, G., Khor, L. Y., Horwitz, E. M., Buyyounouski, M. K., Stoyanova, R. 2017; 109 (2)


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.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.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.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.

View details for DOI 10.1093/jnci/djw232

View details for Web of Science ID 000396774100009

View details for PubMedID 28376214