Prevention Program Targets Pancreatic Cancer Before It Gains a Foothold

Rebecca M. Minter, MD

Alvin Baldwin Jr Chair in Surgery

Professor, Surgery

UT Southwestern Medical Center

Dallas, Texas

Nisa Kubiliun, MD

Director, Endoscopic Services

Assistant Professor, Department of

Internal Medicine

UT Southwestern Medical Center

Dallas, Texas

Pancreatic cancer is currently the fourth-leading cause of cancer death in the United States, with a 5-year survival rate of approximately 8%. Unfortunately, over the past decade, new cases have been increasing on average 0.5% a year, and pancreatic cancer is predicted to be the secondleading cause of cancer death by 2030.^1,2

In an effort to bend this mortality curve, the University of Texas Southwestern Medical Center and Harold C. Simmons Comprehensive Cancer Center in Dallas offer a far-reaching program aimed at detecting pancreatic malignancies early and/or preventing their development in high-risk patients. Currently, only 15% to 20% of patients present with an initially resectable tumor and more than half of pancreatic cancers are discovered after the cancer has widely metastasized.¹

In the UT Southwestern Pancreatic Cancer Prevention Program, radiologists, gastroenterologists, surgical oncologists, cancer genetic counselors, and other providers collaborate in a weekly clinic to evaluate patients with risk factors for pancreatic malignancies and to develop personalized treatment plans.

Patients in the program have an elevated risk for pancreatic cancer due to 1 or more of these risk factors:

• A family history of pancreatic cancer or of other malignancies that can be linked to the disease
• Genetic testing showing mutations associated with increased risk
• Presence within the pancreas of 1 or more mucinous cysts

A Targeted Population

Malignant transformation of pancreatic cysts is relatively uncommon; 1 study estimates an annual US rate of just 0.033%, or about 1137 mucin-producing adenocarcinomas among some 3.4 million total pancreatic cysts.³ However, the current absence of sensitive diagnostic studies to detect progression to cancer limits the ability to truly assess risk for these patients. A core component of the Pancreatic Cancer Prevention Program is ongoing assessment of mucinous cysts for characteristics indicating that they have, or are likely to undergo, malignant transformation.With a lifetime risk in the United States of 1.6%,¹ pancreatic cancer is relatively rare, making universal screening impractical. However, patients with precursor mucinous cystic lesions and those with a hereditary risk represent enriched populations in which screening and surveillance could prove more impactful.

A pillar of the UT Southwestern/Simmons Cancer Center Prevention Program is the incidental discovery of pancreatic lesions on abdominal imaging and the use of electronic medical records to ensure that patients with these lesions are not lost to follow-up.

Concentrated Care

Radiologists at the medical center embed templated language into the patient’s radiology imaging report that flags the often-incidental finding of a pancreatic cyst or other abnormality. This automatically populates a registry within the electronic medical record for the prevention program’s nurse navigator to manage. The nurse navigator then initiates the process for further care, contacting the patient’s primary care and ordering physician for the study that identified the abnormality, providing referral and contact information for the prevention program, alerting program team members, and directing referring physicians to management guidelines for pancreatic abnormalities.Patients referred from elsewhere access the prevention program through a patient intake specialist, who connects them with the nurse navigator. In collaboration with the program’s physician assistants, the navigator collects relevant internal and external medical records; reviews medical and family histories, plus any previous imaging and genetic tests; and gathers further details about cysts that have been detected and related symptoms, if present.

The program’s multidisciplinary team evaluates each case before a patient arrives for consultation. Any procedures needed to better visualize or sample a lesion, such as endoscopic ultrasound (EUS) or additional imaging, are scheduled in the interim, and appointments—all at 1 location—are set with the specific providers each patient needs to see.

Radiologists associated with the program are attuned to findings that may be indicative of cancer. These include whether a cyst has developed septations in its interior, whether the septations have changed since a prior examination, nodularity in the cyst’s walls, and whether the pancreatic duct is obstructed or dilated (Figure).

Figure. Pancreatic Cyst Surveillance Program

Multidisciplinary Review

For patients who undergo EUS, cyst fluid can be sampled and assessed for molecular markers or other precancerous features, and solid masses can be examined for the presence of tumor cells or atypia. Patients with a malignancy are referred directly to UT Southwestern’s Multidisciplinary Pancreatic Cancer Program for treatment. With patient consent, cyst fluid and blood samples are banked and paired with clinical records to support future biomarker research.Once testing is completed, cases are individually reviewed by a full range of specialists in the prevention program’s multidisciplinary conference. The conference includes the same group of experts reviewing each case over time, using imaging that is consistently acquired from visit to visit, allowing for optimal comparisons.

Because pancreatic cysts are clinically challenging, the multidisciplinary group utilizes an evidence-based approach to assess each patient’s personal risk and then recommends a consensus treatment plan. In a minority of cases, the team will recommend removal of a portion or all of the pancreas to prevent the development of pancreatic cancer, or to treat lesions within or throughout the pancreas that are suspicious. More often, customized, long-term surveillance is recommended, and the patients are followed within the program at 6-month to 1-year intervals, depending on the level of concern.

The prevalence of pancreatic cysts noted on imaging typically performed for unrelated reasons is quite high. One study from a major center4 suggests that the rate of incidental detection of pancreatic cysts with magnetic resonance imaging (MRI) is 13.5%, and in patients age 70 and older the cumulative prevalence was 40%.⁴

Although most cysts are benign, 2 types of mucinous cysts are considered potentially premalignant: intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs). IPMNs can affect the entire pancreas, sometimes necessitating complete removal of the organ to excise all at-risk tissue. More frequently, only portions of the pancreas are involved, although ongoing surveillance is required because cystic lesions or pancreatic cancer can develop in the remnant gland post operatively. MCNs are less-common and are unifocal; following their surgical resection, ongoing surveillance of the remaining pancreas is not required if margins were not involved and there was no evidence of cancer.

Genetic Connections

Along with the structural features of a cyst, decisions to operate hinge on the presence of symptoms such as pancreatitis, involvement of the main pancreatic duct, and rapid growth of a cyst. Cysts larger than 3 cm also warrant closer attention, but size alone is not an indication for resection.Several hereditary cancer syndromes involve increased pancreatic cancer risk. These include mutations in the BRCA1 or BRCA2, P16/CDKN2A, or STK11 genes, Lynch syndrome, familial pancreatic cancer, and mutations associated with hereditary pancreatitis.

In appropriate patients, genetic testing is recommended to look for mutations in more than a dozen genes linked to pancreatic cancer, plus several associated with hereditary pancreatitis. Patients with a hereditary risk are counseled on lifestyle changes, such as quitting smoking and ceasing alcohol consumption. Such patients might also undergo annual MRI surveillance of the pancreas to identify any subtle changes that suggest the development of a potential cancer.

Prevention and surveillance measures can also be implemented for the other cancers linked to a hereditary syndrome, such as mammography or breast MRI in people with BRCA mutations, colonoscopy in Lynch syndrome, and skin cancer screenings and sun protection in familial atypical multiple mole melanoma syndrome. The prevention program’s genetic counselors also guide patients on how to talk with family members regarding the potential indications for and benefits of genetic testing.

Since the launch of UT Southwestern’s Pancreatic Cancer Prevention Program in January 2016, more than 350 patients with increased risk for pancreatic cancer have been evaluated. Two-thirds of these patients were referred for cystic neoplasms of the pancreas and approximately one-third for high-risk hereditary conditions.

References

Through this program, patients have been found to have previously unknown germline mutations predisposing them to pancreatic cancer, as well as high-risk lesions that were successfully resected prior to development of pancreatic cancer. The next step in preventing this disease is the identification of biomarkers that can predict which patients are at highest risk; programs such as this one will provide a platform for that critically important work.

References

1. SEER cancer stat facts: pancreas cancer. National Cancer Institute website. seer.cancer.gov/statfacts/html/pancreas.html. Published April 2017. Accessed July 6, 2017.
2. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the United States [erratum in Cancer Res. 2014;74(14):4006]. Cancer Res. 2014;74(11):2913-1921. doi: 10.1158/0008-5472. CAN-14-0155.
3. Gardner TB, Glass LM, Smith KD, et al. Pancreatic cyst prevalence and the risk of mucin-producing adenocarcinoma in US adults. Am J Gastroenterol. 2013;108(10):1546-1550. doi: 10.1038/ ajg.2013.103.
4. Lee KS, Sekhar A, Rofsky NM, Pedrosa I. Prevalence of incidental pancreatic cysts in the adult population on MR imaging. Am J Gastroenterol. 2010;105(9):2079-2084. doi: 10.1038/ajg.2010.122.