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

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

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6379-6388
Number of pages10
JournalClinical Cancer Research
Volume20
Issue number24
DOIs
StatePublished - Dec 15 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'A tissue biomarker -based model that identi fies patients with a high risk of distant metastasis and differential survival by length of androgen deprivation therapy in RTOG protocol 92-02'. Together they form a unique fingerprint.

  • Cite this