Cribriform pattern, Genomic Prostate Score, and adverse pathology at radical prostatectomy in a cohort of prostate cancer patients initially on active surveillance.

Abstract

88 Background: A growing body of literature suggests that the presence of cribriform pattern (CP) in prostate biopsy specimens portends worse outcomes. Furthermore, CP tumors have been found to harbor a myriad of genomic alterations associated with more aggressive disease. We sought to examine the association between CP and Genomic Prostate Score (GPS) and how this association helps predict adverse pathology (AP) at radical prostatectomy (RP) in patients initially managed with active surveillance (AS). Methods: Using the UCSF Urologic Outcomes Database (UODB), we identified 180 AS patients who underwent GPS testing and subsequently RP. Biopsy specimens were re-reviewed centrally to confirm Gleason grade. AP was defined as GS ≥ 4+3, pT3/4, or pN1 on surgical pathology. Clinical and demographic characteristics were compared by CP status using t-tests and chi-squared tests. Cox proportional hazards regression was performed to identify factors associated with AP after adjusting for age, PSA density (log), percentage of positive biopsy cores, biopsy source (UCSF versus outside), and year of diagnosis. Additional models included the base covariates plus presence of CP, GPS, and both CP and GPS. Results: For the cohort, mean age was 60.7 years (SD 7.1) with median PSA of 5.3 ng/ml (interquartile range, IQR 4.2-6.9) at diagnosis. Median PSAD was 0.14 (IQR 0.10-0.20). Among 180 patients, 27 (15%) had CP at biopsy. Mean GPS was significantly higher in CP+ compared to CP- patients (35, SD 12.7 versus 27, SD13.7, p < 0.01), and a greater proportion of CP+ patients had AP compared to CP- (59% versus 54%, p < 0.01). On multivariate analysis, CP was associated with AP (HR 1.9, 95% CI 1.1-3.4, p = 0.02), but significance was lost after adjusting for GPS (p = 0.19). Conclusions: The presence of CP at biopsy was statistically significantly associated with higher GPS. While both were associated with AP at RP, CP was not associated with AP independent of GPS, suggesting an interaction or commonality between these factors not previously explored.