Comparison of Universal Genetic Testing vs Guideline-Directed Targeted Testing for Patients With Hereditary Cancer...

Area of Science:

• Oncology
• Genetics
• Cancer Research

Background:

• Hereditary factors significantly influence cancer risk.
• Identifying germline predispositions impacts cancer management, including screening and treatment.
• Germline testing is crucial for personalized cancer care.

Purpose of the Study:

• To compare the prevalence of pathogenic germline variants (PGVs) detected by universal genetic testing versus guideline-directed targeted testing in cancer patients.
• To assess the uptake of cascade family variant testing (FVT) among patients with identified PGVs.

Main Methods:

• A prospective, multicenter cohort study involving 2984 patients with solid tumors.
• Germline sequencing was performed using a next-generation sequencing platform with over 80 genes.
• Patients were not selected based on cancer type, stage, family history, ethnicity, or age.

Main Results:

• Pathogenic germline variants (PGVs) were detected in 13.3% of patients.
• Universal testing identified 6.4% of patients with clinically actionable findings missed by guideline-based criteria.
• Younger age at diagnosis was the only factor associated with PGV presence.
• Nearly 30% of patients with high-penetrance PGVs had treatment modifications.
• Cascade FVT uptake was low (17.6%) despite being offered at no cost.

Conclusions:

• Universal multigene panel testing increases the detection of heritable cancer variants compared to guideline-directed testing.
• Germline variant findings can lead to significant treatment modifications in a substantial proportion of patients.
• Low uptake of cascade family variant testing highlights a gap in familial risk assessment and intervention.