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

Abstract

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. 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. 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. 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.