OBJECTIVE: To evaluate the occurrence and the oncological predictive value of cribriform growth and/or intraductal carcinoma (CR/IDC) in patients with ISUP grade group (GG) 2 prostate cancer (PCa) at radical prostatectomy (RP) with and without synchronous nodal metastases in a multicenter, international cohort. METHODS: We identified 1060 patients who underwent RP with ISUP GG2 PCa at histopathology and a pelvic lymph node dissection from 3 tertiary referral centers. Of these, 79 (7.4%) had pN1 disease. Case-control matching was performed using the initial prostate-specific antigen (iPSA) value, pT-stage, age, surgical margin status, and referral center as matching variables to compare histopathological characteristics and oncological outcomes between pN1 and pN0 patients. The predictive value of CR/IDC for biochemical recurrence-free survival (BCRFS), defined as the interval between RP and a PSA of ≥0.2ng/mL, and radiological recurrence-free survival (RRFS), defined as the interval between RP and an RR, was evaluated using Cox regression analysis. RESULTS: After case-control matching, 106 patients were included (ie, 53 cases and 53 controls). CR/IDC was significantly more common in pN1 than pN0 RP specimens (100% vs 51%, P<
.001). In pN0 patients, CR/IDC positivity was not associated with BCRFS (hazard ratio [HR]=0.90, 95% CI 0.32-2.55, P=.842) or RRFS (HR 2.45, 95% CI 0.45-13.34, P=.299). pN1 CR/IDC-positive PCa was associated with adverse BCRFS (HR=2.93, 95% CI 1.26-6.83, P=.013) and RRFS (HR=9.19, 95% CI 2.11-40.04, P=.003) in multivariable Cox regression analysis. CONCLUSION: In ISUP GG2 PCa, CR/IDC strongly correlates with synchronous nodal metastases, the latter being associated with adverse outcomes.