The impact of chemotherapy sequencing on resectable pancreatic cancer by stage.

Introduction: While chemotherapy is an important therapeutic modality for pancreatic cancer (PDAC), the optimal sequence of chemotherapy to surgery remains unclear. Further, the precise added benefit of including chemotherapy at each (especially early) stage has not been quantified.

Methods: The National Cancer Database (NCDB) was queried for patients with PDAC who underwent pancreaticoduodenectomy between 2004 and 2016. Cox multivariable and Kaplan-Meier survival analyses were performed for disease-specific survival (DSS) and overall survival (OS) after correcting for confounders. Permutations of chemotherapy/surgery were compared: preoperative only (NCT), postoperative only (ACT), pre- and post-operative (perioperative, PCT), and no therapy (NoT).

Results: 22975 patients met inclusion criteria. 13944(61%) received ACT, 1793(8%) received NCT and 946(4%) received PCT, while 6292(27%) did not receive chemotherapy. Log-rank test showed inferior survival in the NoT group compared to NCT, ACT, and PCT. Compared to the NoT group, PCT had the lowest rate of death (HR 0.704, p < 0.001) followed by NCT (HR 0.721, p < 0.001) and ACT (HR 0.759, p < 0.001).).

Conclusion: PDAC patients receiving chemotherapy, independent of their stage, will result in better DSS and OS. NCT should be given consideration for resectable disease including early stage PDAC and ideally complemented with postoperative chemotherapy. While there was a trend towards improved survival for PCT, NCT and ACT are reasonable options for stages IB-III.