Pancreatic cancer and coexisting diabetes: Survival outcomes from a provincial Canadian cohort.

Abstract

674 Background: Diabetes mellitus (DM) is both a risk factor for and a potential consequence of pancreatic ductal adenocarcinoma (PDAC). Its prognostic role remains controversial, with conflicting evidence regarding its effect on survival. We evaluated the impact of DM on outcomes in a large, population-based cohort of patients (pts) with PDAC. Methods: We conducted a retrospective cohort study of patients with biopsy-proven PDAC diagnosed in Saskatchewan between 2016–2021. Kaplan–Meier estimates were compared by log-rank testing. Multivariate Cox proportional hazards regression identified independent predictors of overall survival (OS) and disease-free survival (DFS). Results: Of the 954 pts, 557 were eligible; 187 (34%) had DM (72% type II, 26% new-onset). Pts with diabetes were older (70 vs. 68 years, p=0.006), had lower BMI (20.1 vs. 21.0, p=0.01), more multimorbidities (84% vs. 42%, p<0.001), and longer symptoms (12 vs. 9 weeks, p=0.04). Surgery was performed in 91 (16%), including 36 diabetic pts. In the entire cohort, 305 (55%) had stage IV disease and 280 (50%) received chemotherapy (49% vs. 51%). In surgically resected sub-cohort, patients with diabetes had shorter DFS (7 months vs. 12 months, p=0.036) and OS (17 months vs. 24 months, p=0.01). DM independently predicted worse OS (HR 1.97, 95% CI 1.17–3.32, p=0.01). (Neo)adjuvant chemotherapy improved DFS (13 months vs. 4 months, HR 2.52, 1.48–4.39, p<0.001) and OS (24 months vs. 9 months, HR 3.38, 1.93–5.92, p<0.001), but pts with diabetes were less likely to complete treatment (48% vs. 67%, p=0.0003). Other adverse predictors were WHO performance status >1 (HR 1.99, 1.18–3.34), positive margin (HR 1.94, 1.16–3.26), lymphovascular invasion (HR 2.07, 1.25–3.41), high BUN (HR 4.47, 1.78–11.3), high bilirubin (HR 2.52, 1.31–4.85), and symptomatic presentation (HR 2.52, 1.02–6.35). Median OS for the entire cohort was 6 months (resectable 17, borderline 14, locally advanced 7, metastatic 3; p<0.001). DM showed a non-significant mortality increase (HR 1.15, 0.96–1.39, p=0.13). Moreover, lack of surgery (HR 2.09, .56–2.79), no chemotherapy (HR 2.49, 2.02–3.10, p<0.001), WHO performance status >1 (HR 1.49, 1.23–1.81), stage III/IV (HR 1.46, 1.13–1.90), abdominal pain (HR 1.23, 1.03–1.47), leukocytosis (HR 1.27, 1.02–1.57), high BUN (HR 1.37, 1.10–1.71), and elevated alkaline phosphatase (HR 1.60, 1.31–1.94) predicted inferior survival. Conclusions: Diabetes independently predicted inferior OS after resection and was associated with lower treatment completion rates. These findings signify that PDAC pts with diabetes represent a high-risk subgroup requiring tailored strategies to optimize treatment delivery and outcomes.