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Five years after the last prostatic carcinoma grading consensus conference of the International Society of Urological Pathology (ISUP), accrual of new data and modification of clinical practice require an update of current pathologic grading guidelines. This manuscript summarizes the proceedings of the ISUP consensus meeting for grading of prostatic carcinoma held in September 2019, in Nice, France. Topics brought to consensus included the following: (1) approaches to reporting of Gleason patterns 4 and 5 quantities, and minor/tertiary patterns, (2) an agreement to report the presence of invasive cribriform carcinoma, (3) an agreement to incorporate intraductal carcinoma into grading, and (4) individual versus aggregate grading of systematic and multiparametric magnetic resonance imaging-targeted biopsies. Finally, developments in the field of artificial intelligence in the grading of prostatic carcinoma and future research perspectives were discussed.

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, diseasespecific 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 ¼ 121), ill-defined 64% (n ¼ 102), cribriform 48% (n ¼ 83), and glomeruloid 25% (n ¼ 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; Po0.001) and disease-specific survival (HR 5.4, 95% CI 2.0-15, P ¼ 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.

Invasive cribriform and intraductal carcinoma in radical prostatectomy specimens have been associated with an adverse clinical outcome. Our objective was to determine the prognostic value of invasive cribriform and intraductal carcinoma in pre-treatment biopsies on time to disease-specific death. We pathologically revised the diagnostic biopsies of 1031 patients from the first screening round of the European Randomized Study of Screening for Prostate Cancer (1993Cancer ( -2000. Ninety percent of all patients (n = 923) had received active treatment, whereas 10% (n = 108) had been followed by watchful waiting. The median follow-up was 13 years. Patients who either had invasive cribriform growth pattern or intraductal carcinoma were categorized as CR/IDC+. The outcome was disease-specific survival. Relationships with outcome were analyzed using multivariable Cox regression and log-rank analysis. In total, 486 patients had Gleason score 6 (47%) and 545 had ≥ 7 (53%). The 15-year disease-specific-survival probabilities were 99% in Gleason score 6 (n = 486), 94% in CR/IDC − Gleason score ≥ 7 (n = 356) and 67% in CR/IDC+ Gleason score ≥ 7 (n = 189). CR/IDC − Gleason score 3+4 = 7 patients did not have statistically different survival probabilities from those with Gleason score 6 (P = 0.30), while CR/IDC+ Gleason score 3+4 = 7 patients did (P o0.001). In multivariable analysis, CR/IDC+ status was independently associated with a poorer disease-specific survival (HR 2.6, 95% CI 1.4-4.8, P = 0.002). We conclude that CR/IDC+ status in prostate cancer biopsies is associated with a worse disease-specific survival. Our findings indicate that men with biopsy CR/IDC − Gleason score 3+4 = 7 prostate cancer could be candidates for active surveillance, as these patients have similar survival probabilities to those with Gleason score 6.

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