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.
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.