Abstract
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.
| Original language | English (US) |
|---|---|
| Journal | Journal of the National Cancer Institute |
| Volume | 109 |
| Issue number | 2 |
| DOIs | |
| State | Published - 2017 |
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ASJC Scopus subject areas
- Medicine(all)
- Oncology
- Cancer Research
Cite this
Prospective validation of diagnostic tumor biomarkers in men treated with radiotherapy for prostate cancer. / Pollack, Alan; Kwon, Deukwoo; Walker, Gail; Khor, Li Yan; Horwitz, Eric M.; Buyyounouski, Mark K.; Stoyanova, Radka.
In: Journal of the National Cancer Institute, Vol. 109, No. 2, 2017.Research output: Contribution to journal › Article
}
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
PY - 2017
Y1 - 2017
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.
UR - http://www.scopus.com/inward/record.url?scp=85018664362&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85018664362&partnerID=8YFLogxK
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 -