ASCO 2017: Association of risk of clinical recurrence and prostate cancer death with a 17-gene genomic prostate score value

Chicago, IL (UroToday.com) In the era of improving detection of clinically meaningful prostate cancer, while not overtreating men who will not derive benefit from treatment, there is increased interest in risk stratification including genomic risk stratifiers. Dr. Phillip Febbo and colleagues presented their study assessing the risk of clinical recurrence (CR) and prostate cancer death (PCD) among patients with genomic prostate score (GPS) value <20 at the prostate cancer poster sessions at the 2017 ASCO annual meeting.

The GPS (scale 0-100) has been validated to predict adverse pathology, biochemical recurrence, metastasis, and prostate cancer death, providing a more accurate overall assessment of patient risk rather than clinical risk factors alone. The objective of the study was to use two large longitudinal prostate cancer cohorts to analyze the risk of clinical recurrence and prostate cancer death for GPS value <20 units. 

For this analysis, two prior GPS studies1,2 were analyzed to establish the risk of clinical recurrence and prostate cancer death associated with a pre-established GPS cut-point of 20. Patients were then divided based on the value of GPS (≤20, >20). Of the 402 patients in Cullen et al. study2 (median follow up 5.2 years), only 5 patients developed metastases, all of which had GPS >20. Among the 426 patients in the Klein et al.1 cohort (median follow up of 6.6 years), there were 109 clinical recurrences (metastasis and local recurrence) and 39 prostate cancer deaths, of which only one patient with events had a GPS <20. In this cohort there were 28% of patients with a GPS <20. Since GPS was developed using Klein et al.1 standardized hazard ratios (std HR, HR for 1 SD change in the covariate) and survival curves for assessing clinical recurrence, prostate cancer death for the two groups was estimated correcting for regression to the mean (RM) and calculating false-discovery rates (FDR). GPS was a significant predictor for both clinical recurrence (std HR 2.50, 95%CI 1.99-3.15; RM-corrected std HR 2.16, FDR <0.1%) and prostate cancer death (std HR 2.90, 95%CI 2.06-4.06; RM-corrected std HR 1.96, FDR <0.1%) after adjustment for AUA group. Men with intermediate risk prostate cancer and a GPS score of < 20 have a 2.6% and 0.7% 10-year RM-corrected risk of clinical recurrence and prostate cancer death, respectively. 

The authors concluded that GPS strongly predicts risk of clinical recurrence and prostate cancer death in men with AUA low- or intermediate-risk prostate cancer. Patients with a GPS score <20 have a very low risk of recurrence and/or prostate cancer mortality. For patients and clinicians unsure about AS based on perceived increased risk, a GPS value <20 may be considered an option for adding information and guiding these decisions.

Presented By: Phillip G. Febbo, MD, Genomic Health, Redwood City, CA, USA

Co-Authors: Michael Crager, Emily Burke, H. Jeffrey Lawrence, Jennifer Cullen, Eric A. Klein

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
Twitter: @zklaassen_md

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA

References:
1. Klein EA, Cooperberg MR, Magi-Galluzzi C, et al. A 17 gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling. Eur Urol 2014 Sep;66(3):550-560.

2. Cullen J, Rosner IL, Brand TC, et al. A Biopsy-based 17-gene Genomic Prostate Score Predicts Recurrence After Radical Prostatectomy and Adverse Surgical Pathology in a Racially Diverse Population of Men with Clinically Low- and Intermediate-risk Prostate Cancer. Eur Urol 2015 Jul;68(1):123-131.