Genetic testing for pancreatic cancer screening: ready for prime time?

Purpose of review: Pancreatic ductal adenocarcinoma (PDAC) has a dismal 13% 5-year survival rate, necessitating early detection and personalized treatment. This review evaluates whether germline genetic testing, integrated with clinical decision support (CDS) tools, is ready for widespread use in PDAC screening. We focus on its potential to identify high-risk individuals (HRIs) beyond those with strong family histories to complex risk and biomarkers, stratifying patients into low-risk and high-risk virtual populations for targeted surveillance.

Recent findings: Germline genetic testing identifies pathogenic variants linked to hereditary cancer syndromes (HCS), enabling multiorgan surveillance and precision oncology (e.g., PARP inhibitors for BRCA2 mutations). Polygenic risk scores (PRS) combined with clinical markers like new-onset diabetes (NOD) increase the positive predictive value (PPV) for PDAC (e.g., 86.7% in high-PRS quintiles). Genetic testing also adjusts for biomarker variability (e.g., CA19-9 levels via FUT2/FUT3 genotyping) and optimizes chemotherapy through pharmacogenetics, reducing toxicity. Comprehensive platforms integrating genetic, clinical, and biomarker data enhance early detection and risk stratification.

Summary: Genetic testing is ready for prime time in PDAC screening. It stratifies patients into low-risk (no surveillance) and high-risk (surveillance warranted) groups, improving early detection, outcomes, and cost-effectiveness, thus transforming PDAC prognosis through targeted intervention.