A tissue biomarker-based model that identifies patients with a high risk of distant metastasis and differential survival by length of androgen deprivation therapy in RTOG protocol 92-02.

Authors

• Alan Pollack
• James J Dignam
• Dayssy A Diaz
• Qian Wu
• Radka Stoyanova
• Kyounghwa Bae
• Adam P Dicker
• Howard Sandler
• Gerald E Hanks
• Felix Y Feng

Publication/Presentation Date

12-15-2014

Abstract

PURPOSE: To examine the relationship between the expression of 7 promising apoptotic/cell proliferation proteins (Ki-67, p53, MDM2, bcl-2, bax, p16, and Cox-2) and risk of distant metastasis.

EXPERIMENTAL DESIGN: RTOG 92-02 compared external beam radiotherapy (EBRT) to approximately 70 Gy + short-term androgen deprivation therapy (STADT) with EBRT + long-term ADT (LTADT). Immunohistochemical analysis was available for ≥4 biomarkers in 616 of 1,521 assessable cases. Biomarkers were evaluated individually and jointly via multivariable modeling of distant metastasis using competing risks hazards regression, adjusting for age, prostate-specific antigen, Gleason score, T stage, and treatment.

RESULTS: Modeling identified four biomarkers (Ki-67, MDM2, p16 and Cox-2) that were jointly associated with distant metastasis. The c-index was 0.77 for the full model and 0.70 for the model without the biomarkers; a relative improvement of about 10% (likelihood ratio P < 0.001). Subdivision of the patients into quartiles based on predicted distant metastasis risk identified a high-risk group with 10-year distant metastasis risk of 52.5% after EBRT + STADT and 31% with EBRT + LTADT; associated 10-year prostate cancer-specific mortality (PCSM) risks were 45.9% and 14.5% with STADT and LTADT.

CONCLUSION: Four biomarkers were found to contribute significantly to a model that predicted distant metastasis and identified a subgroup of patients at a particularly high risk of both distant metastasis and PCSM when EBRT + STADT was used. LTADT resulted in significant reductions in distant metastasis and improvements in PCSM, and there was a suggestion of greater importance in the very high risk subgroup.

Volume

20

Issue

24

First Page

6379

Last Page

6388

ISSN

1557-3265

Published In/Presented At

Pollack, A., Dignam, J. J., Diaz, D. A., Wu, Q., Stoyanova, R., Bae, K., Dicker, A. P., Sandler, H., Hanks, G. E., & Feng, F. Y. (2014). A tissue biomarker-based model that identifies patients with a high risk of distant metastasis and differential survival by length of androgen deprivation therapy in RTOG protocol 92-02. Clinical cancer research : an official journal of the American Association for Cancer Research, 20(24), 6379–6388. https://doi.org/10.1158/1078-0432.CCR-14-0075

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

25294917

Department(s)

Administration and Leadership

Document Type

Article