Evaluating Susceptibility to Pancreatic Cancer

Publication Date: November 20, 2018
Last Updated: December 15, 2022

Assessment

Clinical evaluations of people (with or without pancreatic cancer) should include assessment for possible genetic predisposition syndromes, beginning with a review of family history of cancer (including tumor types and ages at diagnosis for all first and second-degree relatives). (IC, S, B)
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Individuals with a family history of pancreatic cancer affecting two 1st degree relatives meet criteria for familial pancreatic cancer. (IC, S, B)
  • 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.
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Genetic risk evaluation should be conducted in conjunction with health care providers familiar with the diagnosis and management of hereditary cancer syndromes to determine the most appropriate testing strategy and discuss implications of the findings for family members. (IC, S, B)
  • Germline genetic testing for patients with pancreatic cancer should be offered in the context of shared decision making.
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All patients diagnosed with pancreatic adenocarcinoma should undergo assessment of risk for hereditary syndromes known to be associated with an increased risk for pancreatic adenocarcinoma (Table 1). (IC, S, B)
  • 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.
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An individual with a cancer diagnosis is often the best candidate in whom to initiate genetic testing and has the highest likelihood of an informative test result. (IC, S, B)
  • 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
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Genetic testing in a patient with pancreatic cancer may confirm the diagnosis of a hereditary cancer syndrome and inform management of at-risk family members. (IC, M, B/H)
  • 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.
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Several genes have been linked to risk for pancreatic cancer (Table 1). Unless a genetic diagnosis has previously been confirmed in a family member, germline genetic testing should be performed using a multigene panel that includes the genes listed in Table 1. (IC, S, B)
  • 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.
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Pancreatic cancer surveillance can be considered for individuals who are first-degree relatives of individuals with familial pancreatic cancer and/or individuals with a family history of pancreatic cancer who carry a pathogenic germline variant in genes associated with predisposition to pancreatic cancer (Table 1). (IC, M, B/H)
  • 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.
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There is not yet consensus on pathologic targets for surveillance, but the Expert Panel agrees the ultimate goal should be detection and treatment of high-grade dysplasia to prevent invasive cancer. (IC, M, B/H)
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The potential risks of surveillance including the risk of overtreatment, and unnecessary resections should be discussed with the patient. (IC, M, B/H)
  • 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.
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Recommendation Grading

Overview

Title

Evaluating Susceptibility to Pancreatic Cancer

Authoring Organization

Publication Month/Year

November 20, 2018

Last Updated Month/Year

March 4, 2024

Document Type

Other

External Publication Status

Published

Country of Publication

US

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

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Ambulatory

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Assessment and screening

Keywords

pancreatic cancer, Pancreatic Adenocarcinoma, Evaluation, Susceptibility

Source Citation

DOI: 10.1200/JCO.18.01489 Journal of Clinical Oncology 37, no. 2 (January 10, 2019) 153-164.

Supplemental Methodology Resources

Data Supplement, Methodology Supplement

Methodology

Number of Source Documents
95
Literature Search Start Date
January 1, 1998
Literature Search End Date
June 1, 2018
Specialties Involved
Family Medicine, Gastroenterology, Internal Medicine General, Medical Genetics And Genomics, Oncology, Medical Oncology, Oncology