Association of risk of clinical recurrence (CR) and prostate cancer death (PCD) with a 17-gene genomic prostate score (GPS) value <20.

Abstract

5074 Background: Over-treatment of localized prostate cancer (PC) can result from over-estimation of a patient’s risk of CR and PCD. GPS (scale 0-100) has been validated to predict adverse pathology, biochemical recurrence, metastasis, and PCD and provides a more accurate overall assessment of patient risk than clinical risk factors alone. A recent validation study found that no patients with AUA Low- or Intermediate-risk disease and a GPS of <20 developed PC metastases or PCD. Here, 2 large longitudinal PC cohorts were analyzed to estimate the risk of CR and PCD for GPS <or >20 units. Methods: Data from Klein et al. European Urology (EU) 2014 and Cullen et al. EU 2014 were analyzed to establish the risk of CR and PCD associated with a pre-established GPS cut-point of 20. Patients were divided based on the value of GPS (≤20, >20). Cox regression analyses accounted for cohort sampling weights. Since GPS was developed using Klein et al, standardized hazard ratios (std HR, HR for 1 SD change in the covariate) for GPS and CR and PCD survival curves for the 2 groups were estimated correcting for regression to the mean (RM). Results: Of the 402 patients in Cullen et al. (median follow up 5.2 years), only 5 patients developed metastases; all 5 had GPS >20. For Klein et al., of 426 patients with a median follow up of 6.6 years, there were 109 CR (metastasis and local recurrence) and 39 PCD; only one patient with events had a GPS <20. Overall 28% of patients had GPS <20. GPS was a significant predictor for both CR (std HR 2.50 (95%CI 1.99, 3.15, p <0.001, RM-corrected std HR 2.16, FDR <0.1%) and PCD (std HR 2.90 (95% CI 2.06,4.06, p<0.001, 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 CR and PCD, respectively (Table 1). Conclusions: GPS strongly predicts risk of CR and PCD in men with AUA Low- or Intermediate-risk PC. Patients with a GPS score <20 have a very low risk of CR or PCD and should be considered for AS. [Table: see text]