Timing of adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma: A nationwide analysis

BACKGROUND: Guidelines recommend a time to adjuvant chemotherapy (TTC) within 12 weeks after pancreatic ductal adenocarcinoma (PDAC) resection. The aim of this study to evaluate the association between TTC and clinical outcomes in patients undergoing PDAC resection in the Netherlands. METHODS: Patients undergoing upfront, macroscopically radical PDAC resection (2014-2019) in the Netherlands were included. Patients were stratified into receiving no adjuvant chemotherapy, TTC 0-6 weeks, TTC 6-12 weeks, and TTC ≥12 weeks. Multivariable cox and logistic regression analyses were used to assess the association between TTC and overall survival (OS), and between TTC and adjuvant chemotherapy completion. RESULTS: Of 1459 patients, 543 (37 %) did not receive adjuvant chemotherapy, while TTC was 0-6 weeks in 245 (17 %), 6-12 weeks in 612 (42 %), and ≥12 weeks in 59 (4 %) patients. TTC in weeks (HR 0.99, 95 %CI 0.97-1.01, P = 0.39) and different TTC groups were not associated with OS (TTC 6-12 weeks vs TTC 0-6 weeks: HR 1.06, 95 %CI 0.76-1.49, P = 0.72, TTC ≥12 weeks vs TTC 0-6 weeks: (HR 0.62, 95 %CI 0.32-1.21, P = 0.16). Adjuvant chemotherapy completion was associated with improved OS (HR 0.81, 95 %CI 0.51-0.98, P = 0.04). Compared to TTC 0-6 weeks, TTC 6-12 weeks was associated with adjuvant chemotherapy completion (OR 1.57, 95 %CI 1.33-1.84, P < 0.001), while TTC ≥12 weeks was not (OR 1.13, 95 %CI 0.85-1.51, P = 0.39). CONCLUSION: TTC in patients with upfront PDAC resection was not associated with survival, but TTC 6-12 weeks was associated with adjuvant chemotherapy completion. These findings support prioritizing postoperative recovery rather than pushing early adjuvant chemotherapy initiation.