Cribriform architecture outperforms percent Gleason pattern 4 and tertiary pattern 5 in predicting outcome of Grade group 2 prostate cancer patients.

AIMS Gleason pattern 4 (GP4) quantity, invasive cribriform and/or intraductal carcinoma (IC/IDC), and presence of tertiary pattern 5 (TP5) at radical prostatectomy (RP) specimens all add in risk stratification of Grade group (GG) 2 prostate cancer patients. However, it is unclear to what extent these pathological features are mutually related and what is their individual value if investigated simultaneously. Our aims are a) to determine the mutual relation of GP4 quantity, IC/IDC and TP5 in GG2 RP specimens; and b) to assess their prognostic value for biochemical recurrence-free survival (BCRFS). METHODS AND RESULTS Out of 1,064 RP specimens, 472 (44.4%) had GG2 prostate cancer. Men with ≥25% GP4 more frequently had IC/IDC (67.0 % versus 43.9%; P<0.001) and TP5 (20.6% versus 5.8%; P<0.001) than those with <25% pattern 4. In unadjusted analysis, increasing Gleason pattern 4 quantity (Hazard Ratio (HR) 1.3; 95% Confidence Interval (CI) 1.0-1.6; P=0.04) and IC/IDC (log rank P<0.001) were associated with shorter BCRFS, while TP5 (P=0.12) and dichotomized (<25%, ≥25%) percent pattern 4 (P=0.10) were not. In multivariable analysis, IC/IDC carcinoma was an independent prognostic factor (HR 1.9; 95% CI 1.2-2.9; P=0.005) for BCRFS, while continuous or dichotomized percent pattern 4, and TP5 were not. CONCLUSION In conclusion, higher GP4 quantity at RP was associated with more frequent IC/IDC and TP5. IC/IDC was an independent predictor for BCRFS, while percent pattern 4 and TP5 were not. These findings underscore the importance of routinely including presence of IC/IDC in RP pathology reports.