Abstract
BackgroundIntegrated molecular pathology (IMP) approaches based on DNA mutational profiling accurately determine pancreatic cyst malignancy risk in patients lacking definitive diagnoses following endoscopic ultrasound imaging with fine-needle aspiration of fluid for cytology. In such cases, IMP ‘low-risk’ and ‘high-risk’ diagnoses reliably predict benign and malignant disease, respectively, and provide improved risk stratification for malignancy than a model of the 2012 International Consensus Guideline (ICG) recommendations. Our objective was to determine if initial adjunctive IMP testing influenced future real-world pancreatic cyst management decisions for intervention or surveillance relative to ICG recommendations, and if this benefitted patient outcomes.MethodsAnalysis of data from the previously described National Pancreatic Cyst Registry. Associations between real-world decisions (intervention vs. surveillance), ICG model recommendations (surgery vs. surveillance) and IMP diagnoses (high-risk vs. low-risk) were evaluated using 2 × 2 tables. Kaplan Meier and hazard ratio analyses were used to assess time to malignancy. Odds ratios (OR) for surgery decision were determined using logistic regression.ResultsOf 491 patients, 206 received clinical intervention at follow-up (183 surgery, 4 chemotherapy, 19 presumed by malignant cytology). Overall, 13 % (66/491) of patients had a malignant outcome and 87 % (425/491) had a benign outcome at 2.9 years’ follow-up. When ICG and IMP were concordant for surveillance/surgery recommendations, 83 % and 88 % actually underwent surveillance or surgery, respectively. However, when discordant, IMP diagnoses were predictive of real-world decisions, with 88 % of patients having an intervention when ICG recommended surveillance but IMP indicated high risk, and 55 % undergoing surveillance when ICG recommended surgery but IMP indicated low risk. These IMP-associated management decisions benefitted patient outcomes in these subgroups, as 57 % had malignant and 99 % had benign outcomes at a median 2.9 years’ follow-up. IMP was also more predictive of real-world decisions than ICG by multivariate analysis: OR 11.4 (95 % CI 6.0 − 23.7) versus 3.7 (2.4 − 5.8), respectively.ConclusionsDNA-based IMP diagnoses were predictive of real-world management decisions. Importantly, when ICG and IMP were discordant, IMP influence benefitted patients by increasing confidence in surveillance and surgery decisions and reducing the number of unnecessary surgeries in patients with benign disease.
Highlights
Integrated molecular pathology (IMP) approaches based on DNA mutational profiling accurately determine pancreatic cyst malignancy risk in patients lacking definitive diagnoses following endoscopic ultrasound imaging with fine-needle aspiration of fluid for cytology
International and European groups have published consensus recommendations for pancreatic cyst management based on first-line test results [3, 4], recommendations are based mainly on specific cyst histology, which is frequently indiscernible without surgery [5]
An evidence-based approach was recently proposed by the American Gastroenterological Association, the authors noted that the available evidence was of very low quality [5, 6]
Summary
Integrated molecular pathology (IMP) approaches based on DNA mutational profiling accurately determine pancreatic cyst malignancy risk in patients lacking definitive diagnoses following endoscopic ultrasound imaging with fine-needle aspiration of fluid for cytology. In such cases, IMP ‘low-risk’ and ‘high-risk’ diagnoses reliably predict benign and malignant disease, respectively, and provide improved risk stratification for malignancy than a model of the 2012 International Consensus Guideline (ICG) recommendations. A recent estimate derived from a pooled analysis of published literature indicated an invasive adenocarcinoma frequency of 15 % (95 % confidence interval [CI], 12–18 %) in patients with any type of pancreatic cyst undergoing surgery [5]. There is a need for a diagnostic approach that can reliably distinguish cysts that are malignant or likely to become malignant from those that will remain benign, in order to better ascertain which patients require surgery
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