Gleason Pattern 4 with Cribriform Morphology on Biopsy is Associated with Adverse Clinicopathological Findings in a Prospective Radical Prostatectomy Cohort

Abstract The prognostic significance of the Gleason grading system has been well established. However, individual Gleason pattern comprise heterogeneous morphologies which might add additional prognostic information. Recent evidence suggests that Gleason pattern 4 with cribriform growth pattern is associated with an adverse prognosis. To determine the association between cribriform pattern on biopsies and pathological findings on subsequent prostatectomies we evaluated the presence of cribriform architecture in a prospective cohort of 367 men from 2014 to 2018 treated at a single institution. The presence of cribriform morphology on biopsies was correlated with clinicopathological findings on matched radical prostatectomy specimens. Cribriform architecture was present in 63.5% of all biopsies and was correlated with the overall extent of Gleason pattern 4. In addition, cribriform morphology on biopsy showed a statistically significant association with higher Gleason grade and increased pathological stage and nodal metastasis. In a subset analysis of cases with Grade Group 2 (Gleason score 3+4, n=208), these associations did not reach statistical significance, but the presence of cribriform growth in this subgroup showed a trend towards increased upgrading to Grade Group 5 (Gleason score 9/10) (1 (0.5%) vs. 5 (2.4%)), P=0.06). This large prospective study comparing biopsy and prostatectomy finding of cribriform architecture demonstrates that cribriform pattern 4 is associated with adverse prognostic features and highlights the relevance for recognizing specific morphologies with distinct biological and clinical features.