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.
Highlights
The Gleason grading system has a strong predictive value for clinical outcome in prostate cancer patients and is entirely based on architectural growth pattern assessment [1]
The presence of cribriform architecture (Hazard Ratio (HR) 2.1; 95% Confidence Interval (CI) 1.5–2.9; P < 0.001) and comedonecrosis (HR 2.1; 95% CI 1.3–3.2; P = 0.001) were independently associated with biochemical recurrence, as were Prostate-specific Antigen (PSA), Grade Group, pT-stage, positive surgical margins and lymph node status, while single cell/cords, small solid nests and medium to large solid fields were not (Table 3)
Gleason pattern 5 was present in 32% of prostate cancer specimens
Summary
The Gleason grading system has a strong predictive value for clinical outcome in prostate cancer patients and is entirely based on architectural growth pattern assessment [1]. According to the 2014 International Society of Urological Pathology (ISUP) consensus meeting, growth patterns are categorized in three groups; Gleason pattern 3, 4, and 5 [2, 3]. In radical prostatectomy (RP) specimens, the two most common Gleason patterns are added, resulting in a score of 6–10. Men with Gleason score ≤6 (Grade Group 1) on RP have excellent outcome with no or very low risk of developing metastatic disease [4,5,6,7]. Metastasis and disease-specific mortality increments with higher Gleason scores [8,9,10,11,12,13]
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