Time to Treatment Initiation and Risk of Metastatic Progression in Pancreatic Ductal Adenocarcinoma

BACKGROUND AND OBJECTIVES: The association between time to treatment initiation (TTI) and metastatic progression in pancreatic ductal adenocarcinoma (PDAC) remains poorly characterized. We evaluated the association between TTI and subsequent metastasis among patients undergoing curative-intent resection for PDAC. METHODS: Medicare Fee-for-Service beneficiaries aged ≥ 66 years with nonmetastatic PDAC who underwent curative-intent resection from 2017 to 2021 were identified. TTI was defined as the interval from diagnosis to first cancer-directed treatment and modeled continuously per 30-day increase. Three-year metastatic progression was evaluated using Fine-Gray competing-risks regression, with death before metastasis as a competing event. RESULTS: Each 30-day increase in TTI was independently associated with a 14.2% higher subhazard of metastasis (subdistribution hazard ratio [sHR], 1.142; 95% CI, 1.119-1.166; p < 0.001). The association persisted across surgery alone (sHR, 1.130), neoadjuvant therapy followed by surgery (sHR, 1.187), surgery followed by adjuvant therapy (sHR, 1.144), and trimodality therapy (sHR, 1.125) (all p < 0.001). In sensitivity analysis restricted to TTI ≤ 90 days, the association was attenuated and not statistically significant (sHR, 1.064; 95% CI, 0.964-1.174; p = 0.22). CONCLUSIONS: Longer TTI was associated with increased metastatic progression across treatment pathways, although this association was attenuated among patients with TTI ≤ 90 days. Further studies are needed to determine whether treatment timing independently influences metastatic progression.