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Clin Cancer Res. 2014 Dec 15;20(24):6379-88. doi: 10.1158/1078-0432.CCR-14-0075. Epub 2014 Oct 7.

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.

Author information

1
Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida. APollack@med.miami.edu.
2
Department of Public Health Sciences, University of Chicago, Chicago, Illinois; and NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
3
Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida.
4
Early Clinical Biostatistics, Novartis Pharmaceuticals, East Hanover, New Jersey.
5
Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.
6
Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California.
7
Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
8
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.

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.

PMID:
25294917
PMCID:
PMC4299458
DOI:
10.1158/1078-0432.CCR-14-0075
[Indexed for MEDLINE]
Free PMC Article

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