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 - 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 (DM).

Experimental Design: RTOG 92-02 compared external beam radiotherapy (EBRT) to ~70 Gy+short term androgen deprivation therapy (STADT) with EBRT+long term ADT (LTADT). Immunohistochemical analysis was available for ≥4 biomarkers in 616 of 1521 assessable cases. Biomarkers were evaluated individually and jointly via multivariable modeling of DM using competing risks hazards regression, adjusting for age, PSA, Gleason score, T-stage, and treatment.

Results: Modeling identified four biomarkers (Ki-67, MDM2, p16 and Cox-2) that were jointly associated with DM. 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 DM risk identified a high risk group with 10-year DM 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 DM and identified a subgroup of patients at a particularly high risk of both DM and PCSM when EBRT+STADT was used. LTADT resulted in significant reductions in DM and improvements in PCSM, and there was a suggestion of greater importance in this very high risk subgroup.

Written by:
Pollack A, Dignam JJ, Diaz DA, Wu Q, Stoyanova R, Bae K, Dicker AP, Sandler HM, Hanks GE, Feng FY.   Are you the author?
Sylvester Comprehensive Cancer Center - Radiation Oncology, University of Miami Miller School of Medicine; Radiation Therapy Oncology Group, American College of Radiology; Novartis Pharmaceuticals, Early Clinical Biostatistics; Radiation Oncology, Thomas Jefferson University; Radiation Oncology, Cedars-Sinai Medical Center; Radiation Oncology, Fox Chase Cancer Center; Comprehensive Cancer Center, University of Michigan.  

Reference: Clin Cancer Res. 2014 Oct 7. pii: clincanres.0075.2014.
doi: 10.1158/1078-0432.CCR-14-0075

PubMed Abstract
PMID: 25294917

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