Cancer Risk After Initial Surveillance of Intraductal Papillary Mucinous Neoplasms (IPMNs): Are We Missing the Window for Prevention?

Background: The management of intraductal papillary mucinous neoplasms (IPMNs) has evolved through successive International Association of Pancreatology guidelines, aiming to refine surgical indications and improve cancer prevention. With broader adoption of surveillance, the oncologic outcomes of patients resected after follow-up-and the effectiveness of current strategies in preventing malignancy-remain unclear. This study examined how evolving management has influenced surgical selection and cancer prevention, particularly by comparing patients resected at diagnosis versus after surveillance. Methods: Patients with presumed IPMN across four International Association of Pancreatology guideline periods (pre-2006, 2006-2012 [Sendai], 2012-2017 [Fukuoka], and 2017-2024 [Fukuoka revisions]) were analysed by clinical trajectory: follow-up without surgery, upfront surgery (resection within 12 months of diagnosis), and post-surveillance resection (PR). Endpoints included surgical indications and rates of low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive carcinoma (IC). Results: Across guideline periods, patients managed with surveillance increased from 172 before 2006 to 828 in 2006-2012, 1,572 in 2012-2017, and 1,193 after 2017, while PR increased from 11 to 29, 60, and 204, respectively. Overall, among 3,304 patients, 2,452 (74%) were managed with surveillance, 548 (17%) underwent upfront surgery, and 304 (9%) had PR. In the PR group, resections for a single high-risk stigmata (HRS) increased from 9% to 48%, and those with multiple HRS up to 20% after 2017. At pathology, LGD decreased from 46% to 17%, whereas HGD and IC increased from 18 to 28% and from 36 to 45%, respectively. In the upfront surgery group, LGD decreased from 49% to 26%. Development of HRS during follow-up was associated with a higher risk of HGD/IC (odds ratio 2.18, p = 0.008). Conclusions: While evolving IPMN management has reduced rates of LGD and increased detection of HGD, invasive carcinoma remains frequent at resection after surveillance, as surgery is often delayed until HRS emerge. Improved tools are needed to optimize timing and define appropriate oncologic outcomes.