Pancreatic Cancer Risk in Patients With Low-Risk Cystic Lesions.

Importance: Low-risk pancreatic cystic lesions (PCLs) represent common incidental findings with potential for malignant transformation, warranting long-term surveillance. However, data on their long-term cancer risk are limited, leading to inconsistency in current surveillance strategies. Objective: To determine the long-term incidence of pancreatic cancer among patients with low-risk PCLs, and to identify baseline clinical and imaging factors associated with cancer development. Design, Setting, and Participants: This cohort study was conducted among adults (aged ≥18 years) who underwent contrast-enhanced abdominal computed tomography (CT) or magnetic resonance imaging (MRI) between January 1, 2009, and December 31, 2021, at a large, multisite health care system in Massachusetts. MRI or CT scans were screened for PCLs without high-risk stigmata, worrisome features, or coexisting pancreatic mass. Eligible patients with low-risk PCLs were longitudinally followed up. Data analysis was performed from February 2024 to May 2025. Exposures: Baseline demographic, clinical, and imaging characteristics of patients with low-risk PCLs. Main Outcomes and Measures: The outcome was incidence of pancreatic cancer (defined as pathologically confirmed adenocarcinoma, invasive mucinous neoplasms, or high-grade dysplasia). Censoring was defined as absence of pancreatic cancer on imaging follow-up for more than 1 year after the initial examination documenting the PCL. Multivariable cause-specific Cox proportional hazards regression models assessed the associations between baseline factors and incident pancreatic cancer, accounting for death as a competing risk. Associations were reported as hazard ratios (HRs). Risk stratification performance was assessed using Harrell C-statistic and net reclassification index (NRI). Results: Among 499 631 patients reviewed, 6064 with low-risk PCLs were identified and included in the analytic sample, contributing 20 145 person-years of follow-up. Patients had a mean (SD) age at diagnosis of 65.9 (12.3) years and included 3612 females (59.6%). Of the 6064 patients, 38 (0.6%) developed pancreatic cancer, with an incidence rate of 1.89 (95% CI, 1.29-2.49) cases per 1000 person-years, which was higher than the previously reported general population rate of 0.14 cases per 1000 person-years. Twenty-six of 38 patients (68.4%) had cancer that arose from the cyst site, while 12 (31.6%) developed cancer from a different region of the pancreas. Ten patients (26.3%) were diagnosed more than 5 years after initial PCL detection. In multivariable analysis, larger cyst size (HR, 2.24; 95% CI, 1.45-3.48), main pancreatic duct ectasia (HR, 2.84; 95% CI, 1.18-6.84), and older age (HR, 1.04; 95% CI, 1.01-1.07) were associated with cancer. Adding age to a cyst size-based risk stratification model improved estimation of pancreatic cancer risk (NRI, 0.20 [95% CI, 0.03-0.37]; change in C-statistic, 0.14 [95% CI, 0.07-0.22]). Conclusions and Relevance: This cohort study found that low-risk PCLs were associated with a sustained long-term pancreatic cancer risk and were best stratified by combining clinical and imaging factors. Longer than a 5-year follow-up of low-risk PCLs may be warranted to reduce missed or delayed diagnosis of pancreatic cancer.