Evaluating Susceptibility to Pancreatic Cancer
- Individuals whose family history meets criteria for familial pancreatic cancer, those with 3 or more diagnoses of pancreatic cancer in same side of the family, and individuals meeting criteria for other genetic syndromes (Table 1) associated with increased risk for pancreatic cancer have an increased risk for pancreatic cancer and are candidates for genetic testing.
Qualifying Statement. It is important to note that for 90% of families meeting criteria for familial pancreatic cancer, genetic testing does not detect a pathogenic mutation, therefore there may be additional shared epigenetic, genetic, or environmental factors that contribute to pancreatic cancer risk.
- Germline genetic testing for patients with pancreatic cancer should be offered in the context of shared decision making.
- Assessment of risk includes obtaining a personal cancer history and family history of cancers in 1st and 2nd degree relatives. However, recent data demonstrate that many individuals who develop pancreatic cancer in the setting of genetic predisposition lack clinical features or family cancer history typically associated with the corresponding hereditary syndrome. Therefore, germline genetic testing may be discussed with patients with personal history of pancreatic cancer, even if family history is unremarkable.
- However, if a cancer-affected individual is not available, testing may be performed in a pancreatic cancer-unaffected individual following genetic risk assessment with the understanding that a negative test result is considered clinically uninformative.
- The following cancer-unaffected individuals should be offered genetic risk evaluation:
- Members of families with an identified pathogenic cancer susceptibility gene variant
- Pancreatic cancer-unaffected individuals from families that meet criteria for genetic evaluation for known hereditary syndromes that are linked to pancreatic cancer
- Pancreatic cancer-unaffected individuals from families that meet criteria for familial pancreatic cancer, as outlined in PCO 1.2
- Given the possibility that certain germline variants could potentially be used to guide therapeutic decision-making and the limited prognosis of many pancreatic cancer patients, the Expert Panel recommends that consideration of germline testing for inherited cancer susceptibility should be performed early in the disease course for patients with pancreatic cancer.
- A finding of a pathogenic or likely pathogenic germline variant can confer increased risks of cancers beyond the pancreas for the proband and their families.
- Finding a germline variant of uncertain significance is not considered to be causative of increased cancer susceptibility.
- The potential risks, benefits, uncertainties, and limitations of surveillance for pancreatic cancer should be discussed in detail with individuals who are being considered for pancreatic cancer surveillance prior to beginning such surveillance.
- When possible, pancreatic surveillance should be performed at centers with the appropriate expertise to manage individuals at increased risk for pancreatic cancer.
- Surveillance may be performed with various modalities, including pancreas protocol MRI/MRCP and/or endoscopic ultrasound.
- There are currently no approved biomarkers for screening and surveillance.
- CA 19-9 is not recommended as a screening test in the general population due to low specificity and sensitivity; its potential utility in pancreatic screening of high risk individuals has not been established.
Qualifying Statement. Although large studies confirming mortality benefit of pancreatic screening are lacking, emerging data suggest screening in individuals at high risk is associated with downstaging of incident cancers.
- Given the challenges, patients should optimally be managed by an expert multi-disciplinary team with experience in pancreatic cancer surveillance.
- Additional clinical studies are needed to determine the optimal approach for pancreatic surveillance.
Evaluating Susceptibility to Pancreatic Cancer
November 20, 2018
Last Updated Month/Year
December 15, 2022
Supplemental Implementation Tools
External Publication Status
Country of Publication
Target Patient Population
People diagnosed with pancreatic adenocarcinoma and families or individuals with concern for genetic predisposition to pancreatic cancer
Target Provider Population
Primary care physicians, medical oncologists, nurse practitioners, surgeons, gastroenterologists, internists, and other
Female, Male, Adult, Older adult
Health Care Settings
Nurse, nurse practitioner, physician, physician assistant
Assessment and screening
pancreatic cancer, Pancreatic Adenocarcinoma, Evaluation, Susceptibility
DOI: 10.1200/JCO.18.01489 Journal of Clinical Oncology 37, no. 2 (January 10, 2019) 153-164.