BACKGROUND: Many men diagnosed with prostate cancer are active surveillance (AS) candidates. However, AS may be associated with increased risk of disease progression and metastasis due to delayed therapy. Genomic classifiers, e.g., Decipher, may allow better risk-stratify newly diagnosed prostate cancers for AS.
Decipher was initially assessed in a prospective cohort of prostatectomies to explore the correlation with clinically meaningful biologic characteristics and then assessed in diagnostic biopsies from a retrospective multicenter cohort of 266 men with National Comprehensive Cancer Network (NCCN) very low/low and favorable-intermediate risk prostate cancer. Decipher and Cancer of the Prostate Risk Assessment (CAPRA) were compared as predictors of adverse pathology (AP) for which there is universal agreement that patients with long life-expectancy are not suitable candidates for AS (primary pattern 4 or 5, advanced local stage [pT3b or greater] or lymph node involvement).
Decipher from prostatectomies was significantly associated with adverse pathologic features (p-values < 0.001). Decipher from the 266 diagnostic biopsies (64.7% NCCN-very-low/low and 35.3% favorable-intermediate) was an independent predictor of AP (odds ratio 1.29 per 10% increase, 95% confidence interval [CI] 1.03-1.61, p-value 0.025) when adjusting for CAPRA. CAPRA area under curve (AUC) was 0.57, (95% CI 0.47-0.68). Adding Decipher to CAPRA increased the AUC to 0.65 (95% CI 0.58-0.70). NPV, which determines the degree of confidence in the absence of AP for patients, was 91% (95% CI 87-94%) and 96% (95% CI 90-99%) for Decipher thresholds of 0.45 and 0.2, respectively. Using a threshold of 0.2, Decipher was a significant predictor of AP when adjusting for CAPRA (p-value 0.016).
Decipher can be applied to prostate biopsies from NCCN-very-low/low and favorable-intermediate risk patients to predict absence of adverse pathologic features. These patients are predicted to be good candidates for active surveillance.
Prostate cancer and prostatic diseases. 2018 Dec 12 [Epub ahead of print]
Hyung L Kim, Ping Li, Huei-Chung Huang, Samineh Deheshi, Tara Marti, Beatrice Knudsen, Hatem Abou-Ouf, Ridwan Alam, Tamara L Lotan, Lucia L C Lam, Marguerite du Plessis, Elai Davicioni, Neil Fleshner, Brian R Lane, Ashley E Ross, John W Davis, James L Mohler, Bruce J Trock, Eric A Klein, Jeffrey J Tosoian, M Eric Hyndman, Tarek A Bismar
Cedars-Sinai Medical Center, Los Angeles, CA, USA. ., Cedars-Sinai Medical Center, Los Angeles, CA, USA., GenomeDx Inc., Vancouver, BC, Canada., University of Calgary, Calgary, AB, Canada., Johns Hopkins Medical Institutions, Baltimore, MD, USA., University of Toronto, Toronto, ON, Canada., Spectrum Health, Grand Rapids, MI, USA., The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Roswell Park, Buffalo, NY, USA., Cleveland Clinic Glickman Urology and Kidney Institute, Cleveland, OH, USA., University of Calgary, Calgary, AB, Canada. .