Screening for Pancreatic Ductal Adenocarcinoma: Are We Asking the Impossible?-Letter.

Abstract

Caldwell and colleagues (1) highlight several challenges associated with employing a pancreatic cancer screening test. Several questionable assumptions in their study, especially regarding individuals at high risk of pancreatic cancer, limit their conclusions.First, patients with a positive screening test would not proceed immediately to endoscopic ultrasound/fine-needle aspiration (EUS/FNA). Before clinical implementation, the main causes of false-positive screening tests would need to have been determined. Before broad-scale implementation of a screening test, studies would be undertaken to evaluate strategies to limit complications that arise from aggressively pursuing positive screening tests, such as identifying comorbidities that cause false positives and/or repeating screening tests. Furthermore, a test with 90% specificity would generate too many false positives and would be unlikely implemented for pancreatic cancer screening. If a 99%-specificity test was used, patients testing positive could proceed to EUS, where an FNA, which is the main cause of EUS-related complications, would only be performed if a suspicious lesion was detected. Even with a high specificity test, many positive screening tests would be false positives; therefore suspicious-looking, false-positive lesions would rarely be seen on EUS. Second, the authors oversimplify by imposing a scenario whereby all patients with a positive EUS, including false positives, would proceed directly to surgical resection. Pancreatic surgeons do not resect the pancreas indiscriminately. In some cases, pancreatic surveillance imaging identifies worrisome lesions, but clinicians are well aware of the risk benefits of proceeding to surgery. In this setting, the decision to undertake surgery is best decided in a multidisciplinary discussion. As a result, the authors overestimate the morbidity of pancreatic cancer screening. Third, the authors assume all high-risk individuals with germline mutations would undergo pancreatic cancer screening. Pancreatic cancer surveillance is not recommended until middle age (age 50+ for most mutation carriers) when the incidence of pancreatic cancer is greater than the 0.2% the authors estimate.Currently, high-risk individuals typically undergo annual surveillance with pancreatic imaging, with acceptable morbidity, as outlined in the most recent CAPS consensus conference (2). This surveillance strategy is associated with downstaging to resectable disease of diagnosed pancreatic cancers (3, 4), including the detection of stage I cancer, with preliminary evidence of improved survival (3). The pursuit of early detection of pancreatic cancer is still a work in progress, but patients diagnosed with stage I pancreatic cancer who undergo surgical resection have excellent 5- and 10-year survival (5). Therefore, early detection research remains an important strategy to improve the prognosis of pancreatic cancer, especially amongst high-risk individuals.See the Response, p. 975B.W. Katona reports grants from NIH/NIDDK during the conduct of the study; other support from Janssen and Exact Sciences outside the submitted work. R.E. Brand reports grants from Immunovia and Freenome during the conduct of the study. E.M. Stoffel reports the CAPS5 pancreatic cancer screening consortium is funded by NIH (principal investigator: M. Goggins). Many of the authors of this letter are part of this consortium. S. Syngal reports personal fees from Myriad Genetics outside the submitted work. No disclosures were reported by the other authors.This study is supported by Smith Family Research Fund (B.W. Katona), Bowen-Chapman Family Fund (S. Syngal), NIH/NCI grant U01CA210170 (M. Goggins).