Incremental value of DNA analysis in pancreatic cysts stratified by clinical risk factors

Background and Aims: We determined the incremental predictive value of pancreatic cyst fluid molecular analysis to assessing malignancy risk over long-term follow-up of a well-characterized cohort, given the underlying predictive value of imaging parameters routinely used to triage such patients. Methods: Patients who lacked initial cytologic malignancy in cyst fluid and had final pathology or a follow-up period of more than 2 years were included. Patient outcomes determined the malignancy-free survival of patients with high-risk stigmata (HRS), worrisome features (WFs), and DNA abnormalities. DNA analysis included 3 abnormalities: loss of heterozygosity mutations among a panel of tumor suppressor genes, Kras mutation, and elevated DNA quantity. Results: Included were 478 patients; 209 had surgical pathology derived outcomes and 269 had clinical follow-up of >2 years. Eleven percent had malignant outcome. Forty-two patients had HRS, 272 lacked both HRS and WFs, and 164 lacked HRS but had WFs. DNA abnormalities did not statistically change long-term malignancy risk in patients with HRS or in patients lacking both HRS and WFs. Among patients with WFs, the presence of >2 DNA abnormalities significantly increased malignancy risk (relative risk, 5.2; P=.002) and the absence of all DNA abnormalities significantly decreased risk (relative risk,.4; P=.040). Sensitivity analysis confirmed results of survival analysis over differing baseline malignancy probabilities. Conclusions: Our study defines the clinical characteristic of patients in which DNA abnormality testing has the greatest impact on patient outcomes. Use of DNA abnormality testing is supported in a carefully selected patient population limited to cysts with WFs.