Adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma after pathologic complete response to neoadjuvant treatment: necessary or overtreatment?

BACKGROUND: Neoadjuvant treatment (NAT) followed by pancreatectomy is an important strategy to improve outcomes in patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma (PDAC). However, debate persists regarding the value of adjuvant chemotherapy (AC) in patients who receive NAT and achieve a pathologic complete response (PCR). We evaluated whether the use of AC in patients achieving a PCR after NAT and surgical resection is associated with survival.

METHODS: The National Cancer Database was queried for all patients with stage I to III PDAC diagnosed between 2010 and 2021 who received NAT and pancreatectomy. Kaplan-Meier and multivariable Cox hazard regression analyzes were performed to evaluate factors associated with overall survival (OS) based on a PCR status and AC administration.

RESULTS: Among 15,113 individuals who met the inclusion criteria, 509 (3.4%) patients achieved a PCR. Patients who achieved a PCR had a significantly higher median OS compared with those who did not (105.6 vs 25.9 months; P <.001). Among patients who achieved a PCR, the multivariable analysis revealed no significant difference in survival between those who received AC and those who did not (hazard ratio [HR], 0.95; 95% CI, 0.60-1.50; P =.83). However, among patients who did not achieve a PCR, receiving AC was associated with higher OS (HR, 0.80; 95% CI, 0.76-0.84; P <.001).

CONCLUSION: Among patients with PDAC who had a PCR after NAT, receiving AC was not associated with a higher OS. However, receiving AC was associated with a higher OS among patients without a PCR. These findings may help guide individualized treatment recommendations after surgery.