Cribriform and intraductal carcinoma in prostate cancer - implications for risk stratification and therapeutic decision-making.

Abstract

Intraductal carcinoma of the prostate (IDC) and invasive cribriform carcinoma (invasive Crib) are closely related high-risk morphologies that frequently coexist and are associated with adverse pathology, early metastasis and disease-specific mortality across the prostate cancer continuum. These morphologies are common in intermediate- and high-risk disease, but remain under-recognized and inconsistently reported, contributing to undergrading and potentially inappropriate selection of patients for de-escalation strategies such as active surveillance or focal therapy. Biopsy detects these patterns in only about half of affected men, and magnetic resonance imaging (MRI)-targeted sampling does not reliably close this gap. These tumours are enriched for loss of the tumour-suppressor gene PTEN, DNA-damage-repair alterations and genomic instability, and are associated with immunologically 'cold', fibroblast-rich tumour niches. These findings provide a rationale for evaluating biomarker-directed strategies, including inhibition of the PARP and AKT pathways and therapies targeting B7-H3 (also known as CD276). However, definitive evidence that either IDC or invasive Crib predicts benefit from any of these treatments has not been established. A deeper understanding of the biological and clinical behaviour of these tumours, together with rigorous, standardized reporting, is essential for accurate risk stratification, rational use of active surveillance and focal approaches, selection of patients for intensified local and systemic treatment, and the design of biomarker-driven trials for this aggressive disease subset.