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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Invasive cribriform and intraductal carcinoma are associated with adverse clinical outcome in patients with Gleason score 7 prostate cancer. It is yet unclear whether invasive cribriform and intraductal carcinoma of the prostate both have independent prognostic value, or whether field size of invasive cribriform carcinoma has impact on disease outcome. Our objective was to determine the prognostic impact of intraductal and invasive cribriform prostate cancer histological subtypes in radical prostatectomies. We reviewed 420 prostatectomy specimens with ISUP grade 2 prostate cancer, assessed the percentages of Gleason grade 4 and tertiary 5, and performed immunohistochemistry for basal cells to discriminate intraductal from invasive cribriform growth. Small and large invasive cribriform fields were distinguished based on a diameter of at least twice the size of adjacent pre-existent normal glands. Clinicopathological parameters and biochemical recurrence-free survival were used as endpoints. Cribriform architecture was observed in 228 (54.3%) men, 103 (24.5%) of whom had intraductal, 194 (46.2%) small invasive, and 34 (8.1%) large invasive cribriform growth. Large invasive cribriform architecture was associated with older age (P < 0.001), higher percentage Gleason grade 4 (P = 0.001), extraprostatic expansion (P < 0.001), and more frequent lymph node metastases (P = 0.002), when compared with small invasive cribriform and/or intraductal carcinoma. Univariate analysis identified PSA, pT-stage, surgical margin status, and intraductal and invasive cribriform growth as significant predictors for biochemical recurrence-free survival. In multivariable Cox regression analysis, pT-stage (hazard ratio = 1.64, 95% CI: 1.02–2.63, P = 0.04), positive surgical margins (hazard ratio = 3.28, 95% CI: 2.06–5.23, P < 0.001), and large cribriform growth (hazard ratio = 4.36, 95% CI: 2.08–9.17, P < 0.001) were independent predictors for biochemical recurrence-free survival, while intraductal carcinoma, small cribriform growth, and percentage of Gleason grade 4 were not. In conclusion, large cribriform fields represent an aggressive subpattern of invasive cribriform prostate cancer and are an independent predictive factor for biochemical recurrence-free survival in ISUP grade 2 prostate cancer patients.

In conclusion, the applicability of 3D imaging to archival FFPE and fresh clinical specimens offers unlimited opportunities to study clinical and biological topics of interest in their actual 3D context.

E U R O P E A N U R O L O G Y 7 7 ( 2 0 2 0 ) 1 9 1 -1 9 8 a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e u r o p e a n u r o l o g y . c o m Abstract Background: Grade groups (GGs) are an important parameter for therapeutic decision making in prostate cancer (Pca) patients. Invasive cribriform and/or intraductal carcinoma (CR/IDC) has an independent prognostic value for disease outcome, but are not included in the GG limiting their clinical use. Objective: To perform a proof-of-principle study incorporating CR/IDC in the current GG. Design, setting, and participants: All prostate biopsies of 1031 men with screen-detected Pca between 1993 and 2000 were reviewed for the current GG (ranging from 1 to 5) and CR/IDC. The cribriform grade (cGrade) was equal to the GG if CR/IDC was present and GG minus 1 if not. GG1 was cGrade1 if intraductal carcinoma was absent. Intervention: Biopsy review for GG and CR/IDC. A total of 406 patients had received radical prostatectomy (RP), 508 radiotherapy (RT), 108 surveillance, and eight hormonal therapy, and the treatment was unknown for one patient.Outcome measurements and statistical analysis disease-specific survival (DSS), metastasisfree survival (MFS), and biochemical recurrence-free survival (BCRFS) after 15.1 yr (interquartile range 10.9-19.7 yr) follow-up were compared using Harrell's C-statistic. Results and limitations: The biopsy GGs were 486 GG1, 310 GG2, 104 GG3, 64 GG4, and 67 GG5; cGrade distributions were 738 cGrade1, 102 cGrade2, 91 cGrade3, 58 cGrade4, and 42 cGrade5. The cGrade had a better discriminative value than the GG for DSS (C-index 0.79; 95% confidence interval 0.74-0.83 vs 0.76; 0.71-0.82) and MFS (0.79; 0.74-0.84 vs 0.77; 0.72-0.82). The discriminative value for BCRFS after RP and RT was similar for both models. Different diagnostic, such as use of sextant biopsies, and therapeutic strategies in the 1990s are the limitations of this study. Conclusions: The cGrade is a simple Pca grade modification with better discriminative values for DSS and MFS than the GG, particularly impacting decision making in men with current GG2 Pca. Patient summary: Microscopic grading is an important factor for decision making in prostate cancer (Pca) patients. We show that [ 4 5 _ T D $ D I F F ] a simple grade modification better predicts Pca outcome and might improve treatment choices.