Intraductal Carcinoma and Cribriform Pattern in Prostate Cancer: Challenges and Emerging Perspectives

Abstract

Section snippets

Limitations of current strategies for IDC/Crib detection

Reliable detection of these aggressive subtypes remains difficult, as conventional biopsy has demonstrated limited sensitivity. Data from matched biopsy and RP studies indicate that traditional biopsy methods (with or without magnetic resonance imaging [MRI] fusion) have sensitivity as low as 42% for Crib and 44% for IDC detection [4]. Sampling bias in biopsies may explain this, as they are more likely to detect extensive IDC/Crib. In addition, the difficulty in sampling the anterior zone via

Clinical implications of failure to detect IDC/Crib

The landscape of PCa management has evolved, with an emphasis now on risk-adapted approaches that balance treatment intensity with quality-of-life considerations. Active surveillance (AS) is increasingly adopted for favorable intermediate-risk PCa, particularly grade group 2 [GS 7 (3 + 4)], as supported by emerging studies and recognition that not all intermediate-risk cases involve aggressive progression [7]. According to the European Association of Urology guidelines, AS is inappropriate for

IDC/Crib in high-risk PCa

In a study by Yu et al [8], IDC or Crib morphology was observed in 95% of RP specimens with nodal metastases and was a strong independent predictor of prognosis. Incorporation of IDC/Crib in Cancer of the Prostate Risk Assessment and National Comprehensive Cancer Network models enhances their predictive accuracy for BCR after RP, particularly in high-risk and very high-risk groups. This emphasizes the critical need for pathologists to document these features, particularly in cases with biopsy

Imaging for detection of metastasis in IDC/Crib

Prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET)/computed tomography (CT) is increasingly being used in BCR and pretreatment settings. The higher sensitivity of this imaging modality reveals novel metastatic patterns, adding complexity to stage migration [9], [10]. IDC presence in RP specimens correlates with higher likelihood of metastasis on PSMA PET/CT. Among patients with metastasis detected on PSMA PET/CT, Crib is particularly associated with lymphatic

Molecular alterations in IDC/Crib

Both Crib and IDC exhibit higher rates of genetic instability and copy number alterations, frequently involving mutations in key tumor suppressor genes and oncogenes such as PTEN (commonly lost in IDC), TP53, BRCA2, ATM, RB1, and SPOP. Oncogenic pathway deregulation events, including MYC amplification and alterations in the PI3K-AKT-mTOR, JAK-STAT, KRAS, and MAPK pathways, drive tumor progression in these patterns [11]. These molecular changes underscore the aggressive nature of IDC/Crib and

Clinical implications

IDC and Crib morphologies are strongly associated with adverse clinical outcomes, including BCR, metastases, and poor survival. While expansion of AS to favorable intermediate-risk PCa and of focal therapy to unfavorable intermediate-risk cases could offer potential benefits, careful consideration is essential. Accurate detection of high-risk features such as IDC and Crib remains critical, as current biopsy methods often lack sensitivity. Incorporation of these histological features in