Pancreatic cystic neoplasms occur in up to 20 percent of the U.S. adult population, and the incidence increases with more advanced age.1 In recent years, the prevalence of cystic neoplasms of the pancreas appears to be increasing as more patients undergo cross-sectional imaging in both the ambulatory and emergency setting. A recent study of patients undergoing magnetic resonance imaging (MRI) for unrelated symptoms or medical issues identified pancreatic cysts incidentally in nearly 10 percent of patients.2
Pancreatic cystic neoplasms include mucinous cystic neoplasms (MCN) and intraductal papillary mucinous neoplasms (IPMN), which can involve the main pancreatic duct, a side-branch of the main pancreatic duct, or both (mixed type). Main duct IPMN have a 50 percent to 75 percent risk of malignancy; therefore, resection is indicated. The risk of malignancy within side-branch IPMN is more variable and depends on clinical and radiographic features. High-risk features include cysts that are symptomatic, greater than 3 cm in size, associated with regional adenopathy, or have an associated solid component.
In a surgical series of resected high-risk sidebranch IPMN or MCN, approximately 15 to 25 percent harbor malignancy and another 10 percent high-grade dysplasia.3 However, for low-risk cystic neoplasms, the risk of malignancy may be as low as 0.25 percent per year.4 Because of the potential risk of cancer, surveillance imaging for cystic lesions under 3 cm in size in the absence of high-risk features is recommended. However, given the prevalence of cystic lesions in the general population, frequent surveillance testing could result in tremendous health care costs, in addition to patient radiation exposure and scan-related anxiety. Alternatively, pancreatic resection results in significant perioperative morbidity and mortality—approximately 30 percent and 2 percent, respectively (see Figure 1).3,5
Figure 1. Example of a pancreatic cyst (3 cm side-branch IPMN with high-grade dysplasia) on cross-sectional imaging and photograph from surgical resection
Current consensus guidelines
Two major existing consensus guidelines for the management of pancreatic cystic neoplasms are used in the U.S.: the Sendai/ Fukuoka guidelines, published initially in 2012 and revised in 2017, and the American Gastroenterological Association (AGA) guidelines, published in 2015.6-8 Significant differences between the approaches in these two guidelines have led to variations in clinical practice.
The Sendai/Fukuoka guidelines recommend more intensive surveillance and that cysts without high-risk stigmata or worrisome features undergo regular surveillance imaging at appropriate intervals based on cyst size. For lesions 2 to 3 cm in size, endoscopic ultrasound (EUS) is recommended, followed by alternating EUS and MRI at six- to 12-month intervals. For lesions greater than 3 cm, alternating EUS and MRI is recommended at three- to six-month intervals, with careful consideration for resection in young, healthy patients.
In contrast, for low-risk lesions, AGA guidelines recommend MRI one year after initial diagnosis and then MRI every two years for up to five years. Surveillance may be discontinued at five years if no radiographic change occurs in cyst size or features. As evidenced by these very different guideline recommendations, controversy persists regarding the frequency and intensity of surveillance.
New trial seeks to end the controversy
Given the clinical equipoise and lack of a prospectively validated cyst surveillance strategy, researchers have developed the ECOG-ACRIN 2185: Comparing the Clinical Impact of Pancreatic Cyst Surveillance Programs Trial (NCT04239573). In this pragmatic trial, 4,606 patients meeting inclusion criteria will be randomized to either a low-intensity or high-intensity surveillance strategy based on the Sendai/Fukuoka and AGA guidelines, respectively (see Figure 2). This study is unique in its scope and mechanism as candidates can be identified by a range of physicians and providers including not just surgeons, but also primary care, radiology, and gastroenterology physicians—many of whom may be unaccustomed to enrolling patients in cooperative group clinical trials (ECOG-ACRIN, SWOG, NRG, and Alliance).
Figure 2. ECOG-ACRIN 2185 trial schema
The primary endpoints also are distinct, as they have been categorized as either favorable or unfavorable results. Favorable endpoints include high-grade dysplasia and/or resectable very early-stage cancer (T1a N0) at surgery or benign disease and no operation. Unfavorable endpoints include any pancreatic cancer without surgery; >T1a, N0 cancer at surgery; or benign disease at surgery.
Important secondary endpoints will examine all cause pancreatic cancer incidence and mortality, surgical morbidity, resource utilization, and patient-reported outcomes (quality of life, cancer risk perception, and anxiety). The study protocol also includes the collection and banking of radiographic images and tissue and fluid specimens (serum, cyst, urine) at baseline and during the surveillance period for patients who consent to this aspect.
These adjuncts will provide the basis for future correlative science and translational studies to better understand the biology of pancreatic cysts and their progression. Patients will be followed for five years after enrollment.
For any questions about the trial or to accrue, contact the study staff at EA2185_SCOPE@ecog-acrin.org or visit the study page.
1. Stark A, Donahue TR, Reber HA, Hines OJ. Pancreatic cyst disease: A review. JAMA. 2016;315(17):1882-1893.
2. de Oliveira PB, Puchnick A, Szejnfeld J, Goldman SM. Prevalence of incidental pancreatic cysts on 3 tesla magnetic resonance. PLoS One. 2015;10(3):e0121317.
3. Scheiman JM, Hwang JH, Moayyedi P. American gastroenterological association technical review on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology. 2015;148(4):824-848.e822.
4. Wu BU, Sampath K, Berberian CE, et al. Prediction of malignancy in cystic neoplasms of the pancreas: A population-based cohort study. Am J Gastroenterol. 2014;109(1):121-129; quiz 130.
5. Gaujoux S, Brennan MF, Gonen M, et al. Cystic lesions of the pancreas: Changes in the presentation and management of 1,424 patients at a single institution over a 15-year time period. J Am Coll Surg. 2011;212(4):590-600; discussion 600-593.
6. Tanaka M, Fernandez-del Castillo C, Adsay V, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 2012;12(3):183-197.
7. Tanaka M, Fernandez-Del Castillo C, Kamisawa T, et al. Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. Pancreatology. 2017;17(5):738-753.
8. Vege SS, Ziring B, Jain R, Moayyedi P, Clinical Guidelines Committee, American Gastroenterology Association. American Gastroenterological Association Institute guideline on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology. 2015;148(4):819-822; quiz e12-13.