Identifying symptoms associated with diagnosis of pancreatic exocrine and neuroendocrine neoplasms: A nested case-control study of the UK primary care population

Background: Pancreatic cancer has the worst survival rate among all cancers. Almost 70% of patients were diagnosed at Stage IV. Aim: This study aimed to investigate the symptoms associated with the diagnoses of pancreatic ductal adenocarcinoma (PDAC) and neuroendocrine neoplasms (PNEN), comparatively characterise the symptomatology between the two tumour types to inform earlier diagnosis. Design and Setting: A nested case-control study was conducted using data from the QResearch database. Patients aged ≥25 years and diagnosed with PDAC or PNEN during 2000-2019 were the cases. Up to 10 controls from the same general practice were matched with each case by age, sex, and calendar year using incidence density sampling. Methods: Conditional logistic regression was used to investigate the association between the forty-two shortlisted symptoms and the diagnoses of PDAC/PNEN in different timeframes relative to the index date, adjusting for patients’ sociodemographic characteristics, lifestyle, and relevant comorbidities. Results: There were 23,640 patients diagnosed with PDAC and 596 with PNEN. Twenty-three symptoms were significantly associated with PDAC, and nine symptoms with PNEN. Jaundice and gastrointestinal bleeding were the two alarm symptoms for both tumours. Thirst and dark urine were the two new identified symptoms for PDAC. The risk of unintentional weight loss may be longer than two years before the diagnosis of PNEN. Conclusion: PDAC and PNEN have overlapping symptom profiles. The QCancer (Pancreas) risk prediction model could be updated by including the newly identified symptoms and comorbidities, which could help GP identify high-risk patients for timely investigation in primary care