Progression of Unresected Intraductal Papillary Mucinous Neoplasms of the Pancreas to Cancer: A Systematic Review and Meta-analysis

BACKGROUND & AIMS: It is not clear how best to manage patients with low-risk intraductal papillary mucinous neoplasms (IPMNs) of the pancreas because little is known about IPMN progression to cancer. We sought to determine the cumulative incidence of development of pancreatic cancer in persons with unresected IPMNs (particularly low-risk IPMNs). METHODS: We performed a systematic search of the MEDLINE and Embase databases through November 30, 2016 for studies reporting the cumulative incidence of pancreatic cancer in patients with unresected IPMNs or studies that provided data in sufficient detail for us to calculate cumulative incidence values. We categorized patient series as studies on low-risk IPMNs (lesions without main pancreatic duct involvement or mural nodules) or non-low-risk IPMNs. We calculated meta-analytic cumulative incidence values for pancreatic cancer at 1, 3, 5, and 10 years of follow-up by using the inverse variance method and random-effects model. RESULTS: Among 1514 articles screened, we identified 10 studies of low-risk IPMNs (n=2411) and 9 studies of non-low-risk IPMNs (n=825). In studies of low-risk IPMNs, the meta-analytic cumulative incidence values for pancreatic cancer were 0.02% at 1 year (95% confidence interval [CI], 0.0%-0.23%; I-2=0.0%), 1.40% at 3 years (95% CI, 0.58%-2.48%; I-2=58.5%), 3.12% at 5 years (95% CI, 1.12%-5.90%; I-2=88.0%), and 7.77% at 10 years (95% CI, 4.09%-12.39%; I-2=79.8%). These values were much higher in studies of non-low-risk IPMNs; cumulative incidence values for pancreatic cancer were 1.95% at 1 year (95% CI, 0.0%- 5.99%; I-2=84.2%), 5.69% at 3 years (95% CI, 1.10%-12.77%; I-2=89.9%), 9.77% at 5 years (95% CI, 3.04%-19.27%; I-2=92.0%), and 24.68% at 10 years (95% CI, 14.87%-35.90%; I-2=74.3%). The pooled cumulative incidence steadily increased linearly as the follow-up duration increased. CONCLUSIONS: In a systematic review and meta-analysis, we found that low-risk IPMNs have almost 8% chance of progressing to pancreatic cancer within 10 years, and higher-risk IPMNs have almost 25% chance of progressing to cancer in 10 years; incidence values increase linearly with time. Continued long-term surveillance is therefore vital for patients with low-risk IPMNs.