The 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 >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: (1) loss of heterozygosity mutations among a panel of tumor suppressor genes, (2) Kras mutation, (3) and elevated DNA quantity.

RESULTS: 478 patients were included; 209 had surgical pathology derived outcomes and 269 had clinical follow-up of >2 years. 11% had malignant outcome. 42 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 (RR 5.2, P=0.002) and the absence of all DNA abnormalities significantly decreased risk (RR 0.4, P=0.040). Sensitivity analysis confirmed results of survival analysis over differing baseline malignancy probabilities.

CONCLUSION: 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 worrisome features.