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

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

来源：Clinical Cancer Research, 2014, 20(24): 6379-6388.

DOI：10.1158/1078-0432.CCR-14-0075

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. %26lt;br%26gt;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 %26gt;= 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. %26lt;br%26gt;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 %26lt; 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. %26lt;br%26gt;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.

• 出版日期2014-12-15