Morphologic patterns observed in prostate biopsy cases with discrepant grade group and molecular risk classification

Area of Science:

• Urology
• Oncology
• Pathology

Background:

• Molecular-based risk classifiers like the Decipher prostate biopsy test are increasingly used to guide treatment decisions.
• The Decipher test is a 22-gene RNA assay predicting high-grade disease, metastasis, and mortality risk, categorized as low, intermediate, or high.
• This study investigates histologic features in prostate biopsies where the Grade Group (GG) and Decipher risk category were discordant.

Purpose of the Study:

• To examine the histologic characteristics of prostate biopsies with discordant Grade Group (GG) and Decipher molecular risk categories.
• To identify potential reasons for discrepancies between traditional histologic grading and molecular risk assessment.

Main Methods:

• A retrospective review of 178 men with prostate biopsies and Decipher testing (2016-2020) was conducted.
• Discrepancies were defined as GG1-2 with high Decipher risk or GG≥3 with low Decipher risk.
• Biopsy slides were re-reviewed for GG and specific histologic features, including Gleason patterns, high-risk features (e.g., IDC), and difficult-to-grade patterns.

Main Results:

• Of 178 men, 41 (23%) had discordant GG and Decipher risk; 33 slides were reviewed.
• Among these, 23 had GG1-2 with high Decipher risk, often showing difficult-to-grade patterns (e.g., atrophic carcinoma, collagenous fibroplasia).
• Ten had GG≥3 with low Decipher risk, with half exhibiting aggressive histologic patterns like large cribriform or intraductal carcinoma (IDC).

Conclusions:

• Difficult-to-grade patterns are frequently observed in GG1-2 cases with high Decipher risk, suggesting potential underestimation of risk by histology alone.
• Aggressive histologic patterns were present in half of GG≥3 cases with low Decipher risk, indicating that molecular classifiers may not encompass all high-risk histologic features.