Individuals at high risk for pancreatic cancer should at least be considered for screening for the disease, states a new clinical practice update from the American Gastroenterological Association that further defines what constitutes high risk for pancreatic cancer, when and how screenings should occur, and the role of genetic testing and counseling (Gastroenterology. 2020.).
Individuals who have a first-degree relative with two or more genetically related relatives with pancreatic cancer should be considered for screening, as should people with Peutz-Jeghers syndrome, a CDKN2A gene mutation, one or more first-degree relatives with pancreatic cancer with Lynch syndrome and mutations in the BRCA1, BRCA2, PALB2, and ATM genes, the clinical update stated. Screening in high-risk individuals should begin at age 50, but some groups should start having screening earlier: age 40 in carriers of the CKDN2A and PRSS1 mutations with hereditary pancreatitis; and age 35 in those with Peutz-Jeghers syndrome.
“Studies to date have demonstrated variability regarding definitions of high-risk groups and the age at which screening should be initiated,” wrote Harry R. Aslanian, MD, AGAF, of Yale New Haven (Conn.) Hospital, and coauthors. “The genetic basis of much of the inherited susceptibility to pancreas cancer remains unexplained (in approximately 90% of cases) and familial history is important in risk stratification.”
Genetic testing and counseling should be considered for any familial pancreas cancer relative – that is, a person with two or more first-degree relatives with pancreas cancer that’s outside the definition of other hereditary cancers. “A positive germline mutation is associated with an increased risk of neoplastic progression and may also lead to screening for other relevant associated cancers,” wrote Dr. Aslanian and coauthors.
The screening itself should consist of MRI and endoscopic ultrasonography (EUS) in combination, the clinical practice update states. It defines detectable targets as stage 1 pancreatic ductal adenocarcinoma and high-risk neoplasms such as intraductal papillary mucinous neoplasms with high-grade dysplasia and some enlarged pancreatic intraepithelial neoplasms.
High-risk patients having screening should also be enrolled in a registry and referred to a pancreas center of excellence.
The update suggests screening every 12 months when the baseline screening is negative for any suspect lesions, with shorter intervals for EUS when suspected lesions are found: 6-12 months for low-risk lesions; 3-6 months for intermediate lesions; and 3 months for high-risk lesions if the patient hasn’t had surgery to remove the lesions.
Regarding management of positive screening results, a multidisciplinary team should confer with the individual and family to determine therapy. If surgery is indicated, it should be done at a high-volume center.
The update also provides guidance for two scenarios when patients shouldn’t undergo screening: those at average risk; and those at high-risk more likely to die from another cause. Of course, the physician should review the limitations and risk of screening with patients beforehand.
Dr. Aslanian and coauthors noted that a number of areas require further study, including defining the highest-risk groups and refining screening tests with high sensitivity and specificity to detect high-grade precursors, along with more data on risks of precursor lesions themselves.
They also acknowledged the need for more study into the effectiveness of pancreatic cancer screening, although a randomized clinical trial comparing screening vs. no screening “might be challenging to conduct given implementation of clinical screening as standard of care in some practices.” Blood tests for pancreatic cancer screening in high-risk patients also need more study, they stated.
The authors did not report any funding sources or conflicts of interest.
SOURCE: Aslanian HR et al. Gastroenterology. 2020..