Comedonecrosis Gleason pattern 5 is associated with worse clinical outcome in operated prostate cancer patients

Abstract

Individual growth patterns and cribriform architecture are increasingly considered in risk stratification and clinical decision-making in men with prostate cancer. Our objective was to establish the prognostic value of individual Gleason 5 patterns in a radical prostatectomy (RP) cohort. We reviewed 1064 RPs and recorded Grade Group (GG), pT-stage, surgical margin status, Gleason 4 and 5 growth patterns as well as intraductal carcinoma. The clinical endpoints were biochemical recurrence and post-operative distant metastasis. Gleason pattern 5 was present in 339 (31.9%) RPs, of which 47 (4.4%) presented as primary, 166 (15.6%) as secondary, and 126 (11.8%) as tertiary pattern. Single cells/cords were present in 321 (94.7%) tumors with Gleason pattern 5, solid fields in 90 (26.5%), and comedonecrosis in invasive carcinoma in 32 (9.4%) tumors. Solid fields demonstrated either a small nested morphology (n = 50, 14.7%) or medium to large solid fields (n = 61, 18.0%). Cribriform architecture was present in 568 (53.4%) RPs. Medium to large solid fields and comedonecrosis coincided with cribriform architecture in all specimens, and were not observed in cribriform-negative cases. In multivariable analysis adjusted for Prostate-Specific Antigen, pT-stage, GG, surgical margin status and lymph node metastases, cribriform architecture (Hazard Ratio (HR) 9.9; 95% Confidence Interval (CI) 3.9-25.5, P < 0.001) and comedonecrosis (HR 2.1, 95% CI 1.2-3.7, P = 0.01) were independent predictors for metastasis-free survival, while single cells/cords (HR 1.2; 95% CI 0.7-1.8, P = 0.55) and medium to large solid fields (HR 1.6, 95% CI 0.9-2.7, P = 0.09) were not. In conclusion, comedonecrosis in invasive carcinoma is an independent prognostic Gleason 5 pattern for metastasis-free survival after RP. These data support the current recommendations to routinely include cribriform pattern in pathology reports and indicate that comedonecrosis should also be commented on.

Fig. 1. Gleason pattern 5 tumor morphology.

A Single cells and cords, 15×. B Small solid nests, 15×. C Medium to large solid fields, 15×. D Comedonecrosis, 15×.

Fig. 2. Clinical outcome of Grade Group 5 prostate cancer patients without cribriform and solid pattern (CR−/S−; blue line, n = 17), with cribriform but no solid pattern (CR+/S−; orange line, n = 59), and with both cribriform and solid pattern (CR+/S+; green line, n = 43).

Grade Group 5 patients without cribriform and solid pattern (CR−/S−) had significantly better biochemical recurrence-free survival (A; log-rank P < 0.001) and, metastasis-free survival (B, log-rank P = 0.003), while disease-specific survival did not reach significance (C; log-rank P = 0.18).