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Pancreatic Cancer Surveillance: Who Should Be Screened and How Should Screening Be Conducted?

March 15, 2022

Pancreatic adenocarcinoma is notoriously difficult to detect and is often diagnosed at a late stage. As a result, the five-year survival from pancreatic adenocarcinoma is only 10.8%. Population screening for pancreatic cancer is not feasible. Therefore, the first step in identifying pancreatic cancer at an early and potentially resectable stage is narrowing the population to be tested so that surveillance is possible.

Randall E. Brand, MD, Beth Dudley Yurkovich, MS, MPH, CGC, and Eve Karloski, MS, CGC, of the UPMC Hereditary GI Tumor Program, are experts at assessing pancreatic cancer risk based on known risk factors, and are exploring how to improve risk assessment, surveillance protocols, and outcomes in patients with pancreatic adenocarcinoma.

Pancreatic cancer is rare, accounting for only 3.2% of new cancer diagnoses but for 7.9% of cancer deaths in the United States. Finding pancreatic adenocarcinoma when it is potentially resectable and aggressively treating systemic disease is currently the best approach to reduce mortality from pancreatic adenocarcinoma, but this is a formidable challenge. One approach used by the UPMC Hereditary GI Tumor Program is offering pancreatic cancer surveillance to patients who have an increased risk for pancreatic cancer based on family history or hereditary syndromes.

Risk Assessment

There are several situations when a physician might want to refer a patient to the UPMC Hereditary GI Tumor Program based on a family history of pancreatic cancer. Some patients may benefit from risk assessment because they have a first-degree relative (parent, sibling, or child) with pancreatic adenocarcinoma, because there are several family members with pancreatic cancer, or because there is a mix of pancreatic adenocarcinoma and related cancers, including breast, colorectal, and ovarian cancers. Others may be referred to discuss surveillance because they are already known to have an increased risk for pancreatic cancer due to a hereditary syndrome or pathogenic gene variant.

To begin the process of assessing the pancreatic cancer risk in an individual with a genetic syndrome or a family history of pancreatic adenocarcinoma and related cancers, the patient should be referred to the UPMC Hereditary GI Tumor Program, located at UPMC Shadyside. They will meet with a genetic counselor who will compile a detailed personal history and family history to formally assess risk. The genetic counselors can then determine whether genetic testing, if not already performed, is likely to give actionable information that may help the patient. This is a highly individualized process, and genetic testing is not always part of the risk assessment. The patient will also meet with Dr. Brand to discuss a management plan.

The Role of Genetic Testing

All patients with pancreatic adenocarcinoma are offered genetic testing in accordance with current clinical guidelines, which allows for the possibility of targeted therapeutics. Additionally, genetic testing helps identify at-risk family members. Pancreatic cancer risk is associated with pathogenic germline variants in at least 13 genes: APC, ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, and TP53. When an actionable pathogenic gene variant is found in an affected individual, this information can be used to test their family members. First-degree relatives are eligible for testing if their affected family member is not available for testing.

Who Should Be Offered Surveillance?

For many individuals, the risk assessment leads to counseling on preventive strategies, such as healthy eating, not smoking, and exercise. For some, however, we also offer pancreatic cancer surveillance. When considering surveillance, it is crucial that we first evaluate whether the patient could benefit from surveillance. If the individual is not a candidate for surgery, then they are not a candidate for surveillance, because the care team would not be able to act on any findings. The genetic profile and family history then further define candidacy.

All surveillance should be based on expert opinion at a specialty center and should be conducted in the setting of research. We never perform surveillance without first counseling the individual who is concerned about developing pancreatic cancer. Each person needs to understand the risks, benefits, and limitations of surveillance for pancreatic adenocarcinoma. Most proceed with surveillance, but some decline. We are mindful of the emotional stress caused by each round of surveillance and the fact that we cannot guarantee that surveillance will detect pancreatic adenocarcinoma at a potentially resectable, early stage.

Surveillance Protocols

We generally begin surveillance when the high-risk individual is 45-55 years of age or 10 years younger than the youngest age of pancreatic cancer diagnosis in the family, depending on the criteria met. We initiate surveillance at younger ages in individuals with Peutz-Jeghers syndrome or familial atypical multiple mole melanoma (FAMMM) syndrome. Additionally, if an individual determined to be at high risk for pancreatic adenocarcinoma develops new-onset diabetes, surveillance should be initiated.

People who meet pancreatic cancer surveillance criteria are advised to undergo annual imaging of their pancreas by endoscopic ultrasound (EUS) or magnetic resonance imaging (MRI). While a blood test for CA 19-9 is a good marker for pancreatic cancer progression and response to treatment, it is not useful and should not be used in pancreatic cancer screening or surveillance.

Care at UPMC’s Specialty Center

When a pancreatic abnormality is found during imaging, the care team develops a management plan for the patient. At UPMC, we employ a multidisciplinary team approach to pancreatic cancer surveillance and treatment that integrates the expertise of surgeons, gastroenterologists, radiologists, pathologists, certified genetic counselors, and other specialists. Reaching a consensus on treatment as a multidisciplinary team ensures all aspects of patient care are considered for patients. This multidisciplinary approach may also mitigate socioeconomic disparities in care that can affect survival. The team approach at UPMC is helpful when pancreatic cysts are detected during pancreatic cancer surveillance. The expertise accessed through the multidisciplinary clinic is a better resource than any single physician or surgeon in determining how cysts should be managed.

Additionally, when patients come in to see us at UPMC, they are offered the ability to participate in research studies, clinical trials, and research consortiums. We participate in two major pancreatic cancer consortiums—the Cancer of the Pancreas Screening (CAPS) consortium, led by Michael Goggins, MD, at Johns Hopkins University School of Medicine, and the Pancreatic Cancer Early Detection (PRECEDE) consortium. We also participate in the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC). Within the CPDPC, led by our colleague Dhiraj Yadav, MD, MPH, in the Division of Gastroenterology, Hepatology and Nutrition, the new-onset diabetes (NOD) cohort is particularly relevant when considering surveillance in patients at risk for pancreatic adenocarcinoma.

Outcomes of Surveillance

Surveillance with imaging promotes detection of pancreatic adenocarcinoma at an earlier stage in a subset of high-risk individuals. Of 354 high-risk individuals who underwent pancreatic cancer surveillance from 1998 to 2014 as part of the CAPS 1-CAPS 4 consortiums, 24 developed pancreatic adenocarcinoma or high-grade dysplasia. Most (10 adenocarcinoma and 10 high-grade dysplasia) were detected during routine surveillance, but four adenocarcinomas were detected due to symptoms in patients who were either late for annual surveillance or who had discontinued surveillance. Of 10 adenocarcinomas detected during surveillance, nine were resectable. Only one of the tumors detected outside of surveillance was resectable. Additionally, three-year survival for all the patients in this cohort who developed pancreatic adenocarcinoma was 57%, an improvement over three-year survival of approximately 9% for patients with pancreatic adenocarcinoma in the United States during the same timeframe. Whether surveillance will improve survival in larger populations of at-risk individuals is not yet clear, but this data is promising.

Improving Surveillance and Outcomes in the Years Ahead

The success of current surveillance protocols in detecting pancreatic adenocarcinoma at an earlier stage in highly selected patients is encouraging, but the protocols only capture a fraction of pancreatic cancer cases each year. Additional biomarkers for early diagnosis and risk prediction are needed, and their identification, funded through the National Cancer Institute’s Early Detection Research Network, is one of our current research focuses at UPMC. Our Pancreatic Adenocarcinoma Gene Environment Risk (PAGER) study will reveal biomarkers to determine who is at risk for pancreatic adenocarcinoma and who is a good candidate for more invasive tests. Through our research studies and consortium participation, we are striving to develop ways to detect pancreatic cancer earlier, when it may be easier to treat. This is an essential step to improve outcomes for patients with pancreatic cancer and individuals at risk for this deadly disease.

References and Further Reading

Cancer Stat Facts: Pancreatic Cancer: National cancer institute surveillance, epidemiology, and end results program [Available from:]

Hu C, Hart SN, Polley EC, et al. Association between inherited germline mutations in cancer predisposition genes and risk of pancreatic cancer. JAMA. 2018;319(23):2401-9.

Goggins M, Overbeek KA, Brand R, et al. Management of patients with increased risk for familial pancreatic cancer: Updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut. 2020;69(1):7.

Hoehn RS, Rieser CJ, Winters S, et al. A pancreatic cancer multidisciplinary clinic eliminates socioeconomic disparities in treatment and improves survival. Ann Surg Oncol. 2021;28(5):2438-46.

Canto MI, Almario JA, Schulick RD, et al. Risk of neoplastic progression in individuals at high risk for pancreatic cancer undergoing long-term surveillance. Gastroenterology. 2018;155(3):740-51 e2.