More data needed to guide pancreatic cyst management

The growing use of imaging tests in the last decade has led to a significant increase in diagnosed pancreatic cysts. Most are discovered in older adults undergoing abdominal imaging for symptoms unrelated to the pancreas, and may be present in as many as 25 percent of people over age 70.

The majority of incidental cysts, including serous cystadenomas and small branch duct cysts, are not malignant and have little to no malignant potential. Although mucinous cystic neoplasms (MCNs) and some intraductal papillary mucinous neoplasms (IPMNs) can display a range of neoplastic changes, the overall incidence of malignancy is very low.

In a retrospective study published in 2014 in the American Journal of Gastroenterology, Kaiser Permanente researchers reported that 53 (2.9 percent) of 1,815 patients with confirmed pancreatic cystic neoplasm (PCN) were diagnosed with cyst-related malignancy during the study period from 2005 to 2010.

Still, asymptomatic pancreas cysts present challenges for both patients and physicians; patients are understandably anxious about the possibility of cancer, and physicians are confronted with the clinical difficulty of identifying the small subset of cysts with high-grade dysplasia or early cancer. The challenge is complicated by a lack of diagnostic tools with sufficient sensitivity and specificity to identify high-risk patients. Thus, which cysts should undergo surveillance — and for how long — and which should be removed remains a matter of considerable debate.

Guidelines for management: Sendai, Fukuoka and AGA

To provide some guidance about management of IPMNs and mucinous cystic neoplasms, the Sendai consensus guidelines were formulated in 2006 and revised in Fukuoka, Japan, in 2012. Both sets of international consensus guidelines recommended resection of all main-duct IPMNs for patients safely able to tolerate surgery.

The Fukuoka revisions altered the indications for resection of branch-duct IPMNs (BD-IPMNs) when studies suggested that the Sendai size criterion (cysts greater than 3 centimeters) led to unnecessary surgeries. Although BD-IPMNs that aren't resected need ongoing surveillance, neither set of guidelines specified the optimal surveillance interval or method. Furthermore, the Fukuoka guidelines sent mixed signals by recommending surveillance intervals of both six months and two years using alternating CT and magnetic resonance cholangiopancreatography.

In 2015, the American Gastroenterological Association (AGA) published its own guidelines in the journal Gastroenterology. Differing significantly from Sendai and Fukuoka, the AGA recommendations included:

  • MRI surveillance at one year and then every two years for a total of five years for patients with pancreatic cysts less than 3 centimeters (cm) without a solid component
  • EUS-FNA examination of cysts with at least two high-risk features, such as a size greater than 3 cm, an associated solid component or dilated main pancreatic duct. Patients without concerning EUS-FNA findings should undergo MRI surveillance after one year and then every two years thereafter
  • Surgical resection at experienced centers for cysts with both a solid component and dilated pancreatic duct or concerning features on EUS and FNA, with no surveillance after surgery in the absence of invasive cancer or dysplasia
  • Discontinuation of surveillance of pancreatic cysts if there has been no significant change after five years

Suresh T. Chari, M.D., observes that the guidelines are problematic not only because they offer contradictory advice but also because all are based on poor evidence. Dr. Chari is a professor of medicine, a noted pancreas expert and member of the Pancreas Interest Group at Mayo Clinic's campus in Rochester, Minnesota.

"These guidelines, which are alarming for patients and confusing for providers, are mostly opinion because everybody is basing their suggestions on inadequate data and incomplete evidence," he explains. "If one set of guidelines recommends intensive surveillance and another recommends discontinuing it, then where does the truth lie? I'm not saying there is no place for expert opinion guidelines, which have both helped reduce the number of patients eligible for surgery and prevented cancers. I am saying that after 10 years, we should be basing our guidelines on data, not opinions."

One area of concern for Dr. Chari is the recommendation to discontinue surveillance after five years for cysts with no appreciable changes. "Many patients with asymptomatic cysts are elderly, and the cysts will never turn malignant in their lifetime. In the right patients, we should stop surveillance, as we do with colonoscopy. That's common sense. But it's also tricky because if something happens, if cancer does develop, we have to tell patients we can't help them," he says.

Still, the evidence is pointing toward less aggressive interventions. A multinational study published in Gut in 2015 looked at more than 2,600 patients with diagnosed serous cystic neoplasm. Fifty-two percent underwent surgery in the first year after diagnosis, 9 percent had resection after one year and 39 percent did not undergo surgery. Postoperative mortality was 0.6 percent compared with serous cystic neoplasm-related mortality of 0.1 percent. And cyst size did not increase in most patients who did not undergo surgery.

"Our diagnoses are wrong one-third of the time, and 15 percent of the time we remove a cyst that did not need to be removed," Dr. Chari says. "But this is all very nuanced, and it is hard to explain to patients. They are understandably concerned about pancreatic cancer, and even as we move in the direction of longer surveillance intervals, they are negotiating for shorter ones. We can explain to patients why we are following certain things and why other things are off the table because they will never turn into cancer, but there are some people who are never reassured.

"We need a specific test that will definitively identify risk, but we don't have that yet, so we continue using our best judgment. Right now, there is a great need for growth in research and guideline changes to reflect data, not opinion."

For more information

Wu BU, et al. Prediction of malignancy in cystic neoplasms of the pancreas: A population-based cohort study. The American Journal of Gastroenterology. 2014;109:121.

Tanaka M, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 2012;12:183.

Vege SS, et al. American Gastroenterological Association Institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology. 2015;148:819.

Jais B, et al. Serous cystic neoplasm of the pancreas: A multinational study of 2622 patients under the auspices of the Internatinal Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas). Gut. 2016;65:305.