Prognostic impact of large cribriform architecture and intraductal carcinoma of the prostate in diagnostic biopsies of mCSPC receiving ARPI-based therapy

BACKGROUND: A cribriform architecture and intraductal carcinoma of the prostate (IDC-P) are recognized as aggressive histopathological features in prostate cancer. However, their prognostic significance in metastatic castration-sensitive prostate cancer (mCSPC), when assessed from diagnostic biopsy specimens, remains uncertain. METHODS: This retrospective multicenter cohort study included 131 patients with mCSPC who received doublet or triplet therapy incorporating an androgen receptor pathway inhibitor. Diagnostic prostate biopsy specimens were examined for cribriform structures and IDC-P. When the former were present, they were subclassified as small or large types. The primary endpoint was castration-resistant prostate cancer-free survival (CRPC-FS). RESULTS: Large cribriform structures were identified in 54.2% of patients, while small ones were observed in 19.8%. IDC-P was present in 67.2% of cases and was strongly associated with the large-type cribriform architecture (P < .001). Patients with that pattern experienced significantly shorter CRPC-FS compared to those without cribriform structures (P = .013), whereas the small-type architecture was not associated with disease progression. In multivariable analysis, IDC-P and an extent of disease score ≥ 3 were independently associated with shorter CRPC-FS, whereas large cribriform architecture did not retain independent significance. However, incorporation of large cribriform architecture improved model discrimination for predicting castration-resistant prostate cancer progression. CONCLUSIONS: In diagnostic biopsy specimens, the large-type cribriform architecture is associated with adverse outcomes in mCSPC patients receiving androgen receptor pathway inhibitor-based therapy. Although its prognostic impact overlaps with that of IDC-P, its identification at diagnosis may provide clinically relevant information for contemporary mCSPC management.