Early detection of concomitant pancreatic cancer during intraductal papillary mucinous neoplasms surveillance

Pancreatic cancer is known for its rapid progression and often dismal prognosis. The recently published study by Oyama et al., “Intraductal Papillary Mucinous Neoplasm Surveillance Leads to Early Diagnosis and Better Outcomes of Concomitant Cancer”, sheds light on a potential strategy for early detection of pancreatic ductal adenocarcinoma (PDAC) and improved survival rates (1).

This study is the largest to date, prospectively monitoring patients with intraductal papillary mucinous neoplasms (IPMNs) over a 25-year period. It uniquely compares the disease courses of carcinomas arising in three ways: IPMN-associated, non-IPMN-associated, and concomitant with IPMNs. In this context, concomitant PDAC refers to carcinoma occurring alongside an IPMN, but with distinct radiographic and pathological separation. IPMN-associated carcinomas develop directly from an existing IPMN, while non-IPMN-associated carcinomas are diagnosed in patients without IPMNs.

This analysis included 4,620 patients with pancreatic cysts, including 3,638 with IPMNs. Among the IPMN cohort, 132 (3.63%) patients were diagnosed with PDAC, 63 (1.73%) with concomitant PDAC, and 69 (1.90%) with IPMN-derived carcinoma. The study employed a surveillance program with regular specialist visits (every 6–12 months) and relevant tests. The authors adopted a matched-pair study design to compare outcomes between 46 patients with concomitant PDAC and 460 patients with non-IPMN-associated PDAC. The groups were matched on age, sex, and year of diagnosis. Concomitant PDACs were associated with longer overall survival (OS) [median 23.7 months, 95% confidence interval (CI): 14.8–68.3] compared to non-IPMN-associated PDACs (17.1 months, 95% CI: 14.8–19.9) (P=0.034).

The concomitant PDAC incidence rate of 1.73% is lower than reported incidences in existing literature, despite the long follow-up period. The incidence of concomitant PDAC ranges from 2% to 11.2% (2,3). This rate is also slightly lower than the incidence reported by the same study group in 2020 from a different cohort, where 2.14% of a cohort of 1,404 patients with branch-duct (BD)-IPMN developed concomitant PDAC (4). The 2020 study had a shorter follow-up period of 20 years and included only patients with BD-IPMN, which typically have a lower risk of concomitant PDAC than main-branch (MD)-IPMNs (5,6).

Concomitant IPMNs were diagnosed at earlier stages and exhibited higher rates of R0 resection, along with higher OS, in comparison to non-IPMN-associated carcinomas. These distinctions remained significant even after adjusting for lead-time bias. These findings align with a smaller study published in 2011 by Yamaguchi et al., which discovered that IPMN-derived and concomitant carcinomas were notably smaller in size at resection than non-IPMN-associated PDAC (7). Interestingly, non-IPMN-associated PDAC displayed shorter survival durations even when comparisons were restricted to patients with equivalent tumor sizes. The authors inferred that concomitant PDAC might manifest more indolent behaviors. However, Oyama et al. found similar OS times between stage-matched PDAC types, suggesting that survival differences are more likely attributable to earlier diagnosis and candidacy for curative treatment (1).

In this cohort, 57% of concomitant PDAC cases (n=26 of total N=46) had margin-negative (R0) resection, compared to only 21 (n=95 of total N=460) for non-IPMN associated PDACs (P<0.001). R0 resection is the only potentially curative treatment for PDAC and rates vary widely in the literature, ranging from 15% to 53% of patients diagnosed with PDAC (8-15). This highlights the efficacy of the IPMN surveillance program used in this study.

Additionally, existing literature highlights different biological behaviors of MD-IPMNs versus BD-IPMNs. While this study did not specify IPMN morphologies, the original patient population likely included both subtypes. Further analysis exploring the association between IPMN subtypes (gastric, intestinal, or pancreatobiliary) and concomitant PDAC, as well as outcomes based on ductal involvement, would offer valuable insights.

More research is needed to develop and validate an effective surveillance program for concomitant carcinoma. Refined predictive algorithms based on existing clinical data can also identify patients at higher risk of either concomitant PDAC or progression of pancreatic cysts to malignancy.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Gland Surgery. The article has undergone external peer review.

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-24-158/prf

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-24-158/coif). S.G.K. reports research grant funding from Mauna Kea Technologies and Taewoong Medical USA and honoraria for lecture from Mauna Kea Technologies. The other author has no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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