Cullen J., Rosner I.L., Brand T.C., Zhang N., Tsiatis A.C., Moncur J., Ali A., Chen Y., Knezevic D., Maddala T., Lawrence H.J., Febbo P.G., Srivastava S., Sesterhenn I.A., McLeod D.G.
European Urology 2015 68:1 (123-131)
Background: Biomarkers that are validated in independent cohorts are needed to improve risk assessment for prostate cancer (PCa). Objective: A racially diverse cohort of men (20% African American [AA]) was used to evaluate the association of the clinically validated 17-gene Genomic Prostate Score (GPS) with recurrence after radical prostatectomy and adverse pathology (AP) at surgery. Design, setting, and participants: Biopsies from 431 men treated for National Comprehensive Cancer Network (NCCN) very low-, low-, or intermediate-risk PCa between 1990 and 2011 at two US military medical centers were tested to validate the association between GPS and biochemical recurrence (BCR) and to confirm the association with AP. Metastatic recurrence (MR) was also evaluated. Outcome measurements and statistical analysis: Cox proportional hazards models were used for BCR and MR, and logistic regression was used for AP. Central pathology review was performed by one uropathologist. AP was defined as primary Gleason pattern 4 or any pattern 5 and/or pT3 disease. Results and limitations: GPS results (scale: 0’100) were obtained in 402 cases (93%); 62 men (15%) experienced BCR, 5 developed metastases, and 163 had AP. Median followup was 5.2 yr. GPS predicted time to BCR in univariable analysis (hazard ratio per 20 GPS units [HR/20 units]: 2.9; p < 0.001) and after adjusting for NCCN risk group (HR/20 units: 2.7; p < 0.001). GPS also predicted time to metastases (HR/20 units: 3.8; p = 0.032), although the event rate was low (n = 5). GPS was strongly associated with AP (odds ratio per 20 GPS units: 3.3; p < 0.001), adjusted for NCCN risk group. In AA and Caucasian men, the median GPS was 30.3 for both, the distributions of GPS results were similar, and GPS was similarly predictive of outcome. Conclusions: The association of GPS with near- and long-term clinical end points establishes the assay as a strong independent measure of PCa aggressiveness. Tumor aggressiveness, as measured by GPS, and outcomes were similar in AA and Caucasian men in this equal-access health care system. Patient summary: Predicting outcomes in men with newly diagnosed prostate cancer is challenging. This study demonstrates that a new molecular test, the Genomic Prostate Score, which can be performed on a patient’s original prostate needle biopsy, can predict the aggressiveness of the cancer and help men make decisions regarding the need for immediate treatment of their cancer.