Association Between Cribriform Architecture and Tertiary Gleason Pattern 5 in Prostate Cancer: A Cross-Sectional Study of Radical Prostatectomy Specimens

Background/Objectives: Cribriform architecture is an adverse Gleason pattern 4 morphology associated with aggressive prostate cancer outcomes. Tertiary Gleason pattern 5, even as a minor component, may also identify tumors with higher-grade biology not fully captured by conventional Grade Group assignment. We examined whether cribriform architecture is associated with tertiary Gleason pattern 5 in patients undergoing radical prostatectomy. Methods: We performed a retrospective cross-sectional study of radical prostatectomy specimens from patients with prostate adenocarcinoma who underwent radical prostatectomy and had available clinicopathologic data. A centralized pathology review of digitized radical prostatectomy slides was used to assess cribriform architecture. Tertiary Gleason pattern 5 status was obtained from original pathology reports. Multivariable logistic regression was used to evaluate the association between cribriform architecture and tertiary Gleason pattern 5 after adjustment for age, preoperative prostate-specific antigen level, prostatectomy Gleason score, pathologic tumor stage, and margin status. Results: Among 303 patients, 47 (15.5%) had tertiary Gleason pattern 5. Cribriform architecture was more common in tumors with tertiary Gleason pattern 5 than in those without (70% vs. 21%; p < 0.001). On multivariable analysis, cribriform architecture remained independently associated with tertiary Gleason pattern 5 (adjusted odds ratio of 9.46; 95% confidence interval of 4.49–21.0; p < 0.001). The model demonstrated good discrimination, with an area under the receiver operating characteristic curve of 0.80. Conclusions: Cribriform architecture was strongly associated with tertiary Gleason pattern 5. These findings suggest that cribriform-positive tumors may be more likely to harbor minor high-grade pattern 5 components.