TY - JOUR
T1 - Prospective validation of diagnostic tumor biomarkers in men treated with radiotherapy for prostate cancer
AU - Pollack, Alan
AU - Kwon, Deukwoo
AU - Walker, Gail
AU - Khor, Li Yan
AU - Horwitz, Eric M.
AU - Buyyounouski, Mark K.
AU - Stoyanova, Radka
N1 - Funding Information:
This publication was supported in part by grants CA-006927 (Fox Chase Cancer Center cancer center grant) and CA-101984 (PI: A. Pollack) from the National Cancer Institute and grant 09BW-10 Bankhead-Coley Cancer Research Program of the Department of Health, State of Florida (PI: A. Pollack).
PY - 2017/2/1
Y1 - 2017/2/1
N2 - 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 RT6ADT, 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.
AB - 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 RT6ADT, 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.
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U2 - 10.1093/jnci/djw232
DO - 10.1093/jnci/djw232
M3 - Article
C2 - 28376214
AN - SCOPUS:85018664362
VL - 109
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
SN - 0027-8874
IS - 2
ER -