Evaluation of Different National Comprehensive Cancer Network Clinical Practice Guidelines in Prostate Cancer for...

Area of Science:

• Oncology
• Genetics
• Medical Guidelines

Background:

• Germline genetic testing (GGT) is crucial for identifying hereditary cancer predispositions.
• Prostate cancer (PCa) management benefits from understanding genetic risk factors.
• National Comprehensive Cancer Network (NCCN) guidelines provide frameworks for cancer care.

Purpose of the Study:

• To evaluate the efficacy of NCCN guidelines version 1.2022 for germline genetic testing (GGT) in nonmetastatic prostate cancer (PCa) patients.
• To identify PCa patients who would benefit from GGT at a nonmetastatic stage.
• To compare GGT criteria across different NCCN guideline versions.

Main Methods:

• Assessed 376 consecutive patients using NCCN guidelines version 1.2022 for GGT.
• Performed GGT for key PCa-associated genes (ATM, BRCA1, BRCA2, CHEK2, TP53, PALB2, MLH1, MSH2, MSH6, PMS2, HOXB13).
• Analyzed detection rates of pathogenic or likely pathogenic variants (PGVs) and compared criteria across NCCN guideline versions.

Main Results:

• Identified pathogenic or likely pathogenic variants (PGVs) in 12.2% (46/376) of patients.
• High-risk PCa characteristics significantly predicted PGVs (OR 2.19, p=0.01).
• NCCN guideline versions 2.2019 and 3.2024 criteria would have missed five PGV-positive patients compared to version 1.2022.

Conclusions:

• NCCN guidelines version 1.2022 provide a robust framework for GGT in nonmetastatic high-risk PCa.
• GGT should be offered to nonmetastatic PCa patients meeting these criteria to identify high-risk PGVs.
• This approach aids in personalized risk assessment and management strategies for prostate cancer.