Screening for Pancreatic Cancer in People with Genetic Risk
Recently updated clinical practice guidance from the American Gastroenterological Association (AGA) recommends identifying and screening people for pancreatic lesions and pancreatic cancers who are at high risk for the disease due to inherited gene variants or strong family history of pancreatic cancer.
Pancreatic cancer is the third most common cause of cancer death in the United States. It is expected to become the second-leading cause of cancer death by the year 2030. These cancers are hard to detect at an early stage because symptoms are usually subtle or absent and tumors cannot usually be seen or felt during a physical exam. By the time symptoms such as jaundice appear, the cancer has often extended beyond the pancreas or spread to other parts of the body (metastasized).
In recent years, research has highlighted the role of genetics in pancreatic cancer risk. According to the updated AGA guidance, about 3 to 5% of pancreatic cancer cases are caused by inherited genetic syndromes, while 5 to 10% of cases are due to familial pancreatic cancer (a strong family history of pancreatic cancer but doesn’t meet criteria for inherited syndromes). The average lifetime risk of pancreatic cancer in the general population is about 1.3%. The lifetime risk in people with two first-degree relatives (parents, siblings, children) with pancreatic cancer is 8 to 12%. The lifetime risk increases to 40% in people with three or more affected first-degree relatives.
Magnetic resonance imaging (MRI) and endoscopic ultrasonography (EUS) are the primary recommended screening methods. These imaging tests have been shown to be sensitive for finding pancreas lesions. Screening aims to find both early pancreatic cancers and lesions likely to become cancerous before signs and symptoms appear and before the cancer spreads.
The clinical practice update emphasizes opportunities for early detection and increasing chances of survival in patients with genetic risk. People at average risk for pancreatic cancer do not need screening, the guidance notes. However, healthcare practitioners should consider pancreatic screening for parents, siblings, and children of individuals with pancreatic cancer, particularly those who have more than two affected biological family members.
Healthcare professionals should also consider screening in patients with Peutz-Jeghers syndrome (PJS), an inherited cancer predisposition disorder associated with a STK11 gene variant that causes gastrointestinal polyps and skin freckling, as well as increased risk of other cancers. Very high risk is also associated with familial pancreatitis, caused by a PRSS1 gene variant. Individuals with one or more close biological relatives with Lynch syndrome, the most common cause of hereditary colon cancer, may also warrant screening. The guidance suggests that healthcare practitioners also consider screening patients with known pathogenic (disease-causing) variants in the genes CDKN2A, BRCA1, BRCA2, PALB2, and ATM.
The guidance recommends that genetic counseling and testing be considered for relatives in cases of familial pancreatic cancer; however, it does not comment on use of any specific genetic testing to uncover genetic risk factors. The guidance also notes that identifying an inherited genetic change associated with an increased risk of pancreatic cancer may be a reason to screen for other associated cancers. (For information on examples of genetic tests, see the links in Related Content.)
Screening for pancreatic cancer should begin at age 50, or 10 years before the age when the youngest affected family member was diagnosed. People with pathogenic variants in the CDKN2A and PRSS1 genes should be screened starting at age 40 and people with PJS should begin pancreatic cancer screening by age 35.
The timing of subsequent screening depends on the result of the initial screen. For example, if a first screening shows no concerning lesions, patients are typically re-screened every year, whereas re-screening for those with high-risk lesions is typically performed every 3 months (if no surgery is planned). If a pancreatic lesion is found, a fine-needle aspiration biopsy may be performed in follow-up.
The guidance notes that further research is needed to define those who are at high risk for pancreatic cancer in order to improve the sensitivity and specificity of screening tests, as well as to develop blood tests, such as tests for circulating tumor DNA, that could be useful screening tools for pancreatic cancer.
Aslanian HR et al. AGA clinical practice update on pancreas cancer screening in high risk individuals: Expert review. Gastroenterology. Available online at https://doi.org/10.1053/j.gastro.2020.03.088. Published May 13, 2020. Accessed June 17, 2020.
Douglas G. Adler. Expert Guidance on Pancreatic Cancer Screening in High-Risk Individuals. NEJM Journal Watch. Available online at https://www.jwatch.org/na51753/2020/06/08/expert-guidance-pancreatic-cancer-screening-high-risk?ijkey=WQwjAFex_. Published June 8, 2020. Accessed June 17, 2020.
Harry R. Aslanian, Jeffrey H. Lee, and Marcia Irene Canto. AGA Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals: Expert Review. Gastroenterology. 2020; 1-5.