Cribriform Tumor Burden in Grade Group 4 Prostate Cancer: A Quantitative Threshold Predicting Lymphovascular Invasion and Metastasis

TL;DR

This study shows that measuring the amount of cribriform tumor burden in prostate cancer helps predict aggressive disease and metastasis better than simple assessments.

Contribution

The study identifies a quantitative threshold (≥25%) of cribriform tumor burden as a novel predictor of lymphovascular invasion and metastasis in Grade Group 4 prostate cancer.

Findings

A CTB threshold of ≥25% was strongly associated with lymphovascular invasion (LVI) and intraductal carcinoma.

High CTB was independently linked to LVI and shorter distant metastasis-free survival.

Quantifying CTB improved risk stratification compared to binary assessments.

Abstract

Background/Objectives: Although the presence and diameter of the cribriform pattern (CP) are established prognostic factors in prostate cancer (PCa), the clinical impact of quantitative cribriform tumor burden (CTB) remains poorly characterized. This study aimed to evaluate the association between CTB and clinicopathological outcomes in Grade Group 4 PCa with large cribriform morphology (LC-GG4). Methods: We retrospectively analyzed patients with pure GG4 prostate cancer exhibiting ≥1 large cribriform gland (>0.25 mm) at radical prostatectomy. CTB was assessed as the percentage of cribriform architecture relative to the total tumor area. Following clinicopathological correlation, receiver operating characteristic (ROC) analysis determined the optimal CTB threshold for predicting lymphovascular invasion (LVI). Distant Metastasis-free survival (dMFS) and biochemical recurrence-free survival (BCRFS) were evaluated using the Kaplan–Meier and log-rank tests. Results: In 43 patients with LC-GG4, extraprostatic extension was present in 100% of cases. The median CTB was 30.0% (IQR: 15.0–60.0%). A CTB threshold of ≥25% was optimally associated with LVI (area under the curve [AUC]: 0.801, p = 0.002). High-CTB (≥25%) was strongly correlated with LVI (p = 0.002) and intraductal carcinoma (p = 0.004) and was independently associated with LVI in multivariate analysis (OR: 1.054; p = 0.006). Furthermore, high-CTB patients demonstrated significantly shorter mean dMFS (84.9 vs. 113.1 months; p = 0.042), with no significant difference observed for BCRFS. Conclusions: In LC-GG4 prostate cancer, CTB is a critical determinant of clinical aggressiveness. A quantitative threshold of ≥25% was independently associated with LVI and early metastatic progression. Quantifying CTB, rather than relying on simple binary assessment, provides superior risk stratification.

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