Development of a Model for Differentiating PDAC from Benign Pancreatic Conditions: A Prospective Case-control Study

Background & aims Pancreatic ductal adenocarcinoma (PDAC) continues to be a devastating disease with late diagnosis and poor overall survival, complicated by clinical presentations similar to benign pancreatic diseases. We aimed to analyse clinical parameters with the goal of developing a prediction model for differentiating suspected PDAC from benign pancreatic conditions. Methods and results We used a prospectively recruited cohort of patients with pancreatic disease (n=762) enrolled at the Barts Pancreas Tissue Bank between January 1, 2008 and September 21, 2021 to perform a case-control study examining the association of PDAC (n=340) with predictor variables including demographics, comorbidities, lifestyle factors, presenting symptoms and commonly performed blood tests. Using a machine learning approach, candidate PDAC risk-prediction algorithms were trained on 75% of the cohort, using a subset of the predictor variables identified from a preliminary observational association study. Models were assessed on the remaining 25%. Multiple imputed datasets were used for both training and validation to accommodate for unknown data. Age (over 55), weight loss in hypertensive patients, recent symptom of jaundice, high serum bilirubin, low serum creatinine, high serum alkaline phosphatase, low lymphocyte count and low serum sodium were the most important features when separating putative PDAC cases from less severe pancreatic conditions. A simple logistic regression model had the best performance with an area under the curve (AUC) of 0.88. Setting a probability threshold of 0.17 guided by the maximum F 2 score, a sensitivity of 95.6% was reached in the full cohort which could lead to early detection of around 84% of the PDAC patients. Conclusion The resultant prediction model significantly outperformed the current UK guidelines for suspected pancreatic cancer referral and could improve detection rates of PDAC in the community. After further work this approach could lead to an easy to understand, utilisable risk score to be applied in the primary and secondary care setting for referring patients to specialist hepato-pancreatico-biliary services. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study is conducted under the umbrella research tissue bank Pancreatic Cancer Research Fund Tissue Bank, funded by Pancreatic Cancer Research Fund. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All data utilised for this research were collected from the Barts Pancreas Tissue Bank study, with written informed consent from patients recruited at Barts Health NHS Trust (BHNT) (Hampshire B Research Ethics Committee: 18/SC/0630). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to Barts Pancreas Tissue Bank. * AUROC : (area under the receiver operating characteristic) BHNT : (Barts Health NHS Trust) BMI : (body mass index) BPTB : (Barts Pancreas Tissue Bank) CDST : (cancer decision support tool) CI : (confidence interval) EHR : (electronic health records) HPB : (hepato-pancreatico-biliary) LR : (logistic regression) NICE : (National Institute for Health and Care Excellence) OR : (odds ratio) PDAC : (pancreatic ductal adenocarcinoma) PnC : (non-malignant pancreatic diseases) ROC : (receiver operating characteristic)