Hereditary Pancreatic Cancer Risk Management: Interpreting Surveillance Findings in High-Risk Patients

Mehul Trivedi, MD - Communications Committee Member

We were delighted to welcome Dr. Fay Kastrinos, Professor of Medicine at Columbia University and Director of the GI Cancer Risk and Prevention Clinic and Pancreatic Cancer Prevention and Genetics Program, who shared her expertise on current strategies, outcomes, and emerging approaches to pancreatic cancer screening in high-risk individuals.

We began by reviewing the goals of pancreatic cancer screening, emphasizing the importance of detecting early-stage pancreatic ductal adenocarcinoma (PDAC) and high-grade precursor lesions that may be amenable to resection. While population-wide screening is not recommended, individuals with a hereditary or familial predisposition to pancreatic cancer may benefit from surveillance. Dr. Kastrinos reviewed current criteria for identifying high-risk individuals, including those with pathogenic germline variants and significant family histories, highlighting the evolving role of genetic testing and expanding screening eligibility for certain mutation carriers even in the absence of a family history of pancreatic cancer.

Dr. Kastrinos then discussed current surveillance strategies, which primarily rely on annual MRI/MRCP and endoscopic ultrasound (EUS). She reviewed findings from the Cancer of the Pancreas Screening (CAPS) studies, which demonstrated that surveillance among high-risk individuals was associated with detection of smaller, earlier-stage cancers, improved survival, and reduced pancreatic cancer-related mortality. She also highlighted recent findings from the PRECEDE consortium, which evaluated pancreatic imaging abnormalities among carriers of pathogenic variants in BRCA1, BRCA2, PALB2, and ATM. Although nearly 60% of participants had pancreatic imaging findings, most were benign cystic lesions, underscoring the challenges of distinguishing clinically significant abnormalities from incidental findings. We then discussed the limitations of surveillance, including its relatively low diagnostic yield, resource-intensive nature, and inability to reliably identify high-grade dysplasia.

The discussion then shifted toward opportunities to improve risk stratification and early detection. Dr. Kastrinos highlighted new-onset diabetes as a potential early marker of pancreatic cancer, particularly among older individuals with lower body mass index or unexplained weight loss. She also reviewed emerging blood-based biomarkers, including cell-free DNA methylation assays and multi-analyte tests such as Avantect and PancreaSure, which have demonstrated promising sensitivity and specificity for early-stage PDAC in validation studies. While these technologies may eventually complement imaging surveillance, their clinical utility in asymptomatic high-risk populations remains uncertain. She emphasized the need for larger prospective studies to determine whether biomarkers could help personalize surveillance intervals, identify individuals requiring more intensive imaging, or reduce unnecessary procedures.

The Q&A session explored several challenges in pancreatic cancer risk assessment and surveillance, including the role of prediction models, the utility of HbA1c and new-onset diabetes, and screening considerations for individuals with less clearly defined familial risk. Dr. Kastrinos emphasized the importance of obtaining a comprehensive family history, particularly when germline testing is unavailable or patients do not meet established screening criteria. The discussion also addressed managing incidentally identified hereditary pancreatitis variants and applying pancreatic cyst guidelines in high-risk populations.

A recurring theme was the need to move beyond a uniform surveillance approach toward more individualized, risk-adapted strategies that incorporate genetic, clinical, imaging, and potentially molecular biomarkers.

Many thanks to Dr. Kastrinos for sharing her expertise and insights into the evolving landscape of pancreatic cancer screening, and to everyone who joined the discussion. We look forward to seeing you at the next CGA-IGC webinar!

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