Cribriform architecture in radical prostatectomies predicts oncological outcome in Gleason score 8 prostate cancer patients

Abstract

The Gleason score is an important parameter for clinical outcome in prostate cancer patients. Gleason score 8 is a heterogeneous disease including Gleason score 3 + 5, 4 + 4, and 5 + 3 tumors, and encompasses a broad range of tumor growth patterns. Our objective was to characterize individual growth patterns and identify prognostic parameters in Gleason score 8 prostate cancer patients. We reviewed 1064 radical prostatectomy specimens, recorded individual Gleason 4 and 5 growth patterns as well as presence of intraductal carcinoma, and evaluated biochemical recurrence- and metastasis-free survival. Gleason score 8 disease was identified in 140 (13%) patients, of whom 76 (54%) had Gleason score 3 + 5, 46 (33%) 4 + 4, and 18 (13%) 5 + 3 disease. Invasive cribriform and/or intraductal carcinoma (n = 87, 62%) was observed more frequently in Gleason score 4 + 4 (93%) than 3 + 5 (47%; P < 0.001) and 5 + 3 (44%; P < 0.001) patients. Gleason pattern 5 was present in 110 (79%) men: as single cells and/or cords in 99 (90%) and solid fields in 32 (29%) cases. Solid field pattern 5 coexisted with cribriform architecture (23/32, 72%) more frequently than nonsolid pattern 5 cases (36/78, 46%, P = 0.02). In multivariable analysis including age, prostate-specific antigen, pT-stage, surgical margin status, and lymph node metastases, presence of cribriform architecture was an independent parameter for biochemical recurrence-free (hazard ratio (HR) 2.0, 95% confidence interval (CI) 1.0-3.7; P = 0.04) and metastasis-free (HR 3.5, 95% CI 1.0-12.3; P = 0.05) survival. In conclusion, invasive cribriform and/or intraductal carcinoma occurs more frequently in Gleason score 4 + 4 prostate cancer patients than in Gleason score 3 + 5 and 5 + 3, and is an independent parameter for biochemical recurrence and metastasis. Therefore, cribriform architecture has added value in risk stratification of Gleason score 8 prostate cancer patients.

Fig. 1. Gleason pattern 4 and pattern 5 tumor morphology.

a Gleason pattern 4, small invasive cribriform structures, 15×. b Gleason pattern 4, large invasive cribriform structures, 10×. c Gleason pattern 5, cords, 20×. d Gleason pattern 5, small solid nests with subtle intervening stroma, 20×. e Gleason pattern 5, medium to large sized solid fields, 15×. f Gleason pattern 5, comedonecrosis in a solid field, 15×.

Fig. 2. Survival curves stratified for individual Gleason score.

Kaplan–Meier curves of a biochemical recurrence-free survival (log rank P = 0.001), b metastasis-free survival (log rank P < 0.001), and c disease-specific survival (log rank P = 0.01) in Gleason score 8 patients stratified for individual Gleason score.

Fig. 3. Survival curves stratified for cribriform architecture.

Kaplan–Meier curves of a biochemical recurrence-free survival (log rank P = 0.001), b metastasis-free survival (log rank P < 0.001), and c disease-specific survival (log rank P = 0.01) in Gleason score 8 patients with invasive and/or intraductal cribriform carcinoma (CR/IDC+) and without invasive and/or intraductal cribriform carcinoma (CR/IDC−).