Patients with Gleason score 7 prostate cancer on radical prostatectomy 
demonstrate a wide range in clinical outcome. Gleason grade 4 prostate cancer 
encompasses a heterogeneous group of tumor growth patterns including fused, 
ill-defined, cribriform, and glomeruloid glandular structures. Our objective was 
to determine the prognostic value of different Gleason grade 4 growth patterns. 
We performed a nested case-control study among 535 patients with Gleason score 7 
prostate cancer at radical prostatectomy, treated between March 1985 and July 
2013 at a university hospital in the Netherlands. We analyzed 52 cases (with 
metastasis, disease-specific mortality or both) and 109 controls, matched for 
age, PSA level, and pT stage. Presence of the following Gleason grade 4 patterns 
was recorded: fused, ill-defined, cribriform, and glomeruloid. Intraductal 
carcinoma of the prostate and tertiary Gleason grade 5 were additionally 
assessed. Outcomes were metastasis-free survival and disease-specific survival. 
We used Cox proportional hazards regression to determine the predictive value of 
Gleason grade 4 patterns for survival time. The overall prevalence of Gleason 
grade 4 patterns was as follows: fused 75% (n=121), ill-defined 64% (n=102), 
cribriform 48% (n=83), and glomeruloid 25% (n=40). Cribriform pattern was the 
only pattern with an unequal distribution between cases and controls. Forty-two 
out of 52 cases (81%) had cribriform growth pattern versus 41/109 controls 
(38%). In multivariate analysis, presence of cribriform growth was an adverse 
independent predictor for distant metastasis-free survival (HR 8.0, 95% CI 
3.0-21; P<0.001) and disease-specific survival (HR 5.4, 95% CI 2.0-15, P=0.001). 
In conclusion, cribriform growth in Gleason grade 4 is a strong prognostic 
marker for distant metastasis and disease-specific death in patients with 
Gleason score 7 prostate cancer at radical prostatectomy.