Neoadjuvant Gemcitabine Plus S-1 for Resectable Pancreatic Ductal Adenocarcinoma: A Propensity Score-matched Study

Neoadjuvant chemotherapy with gemcitabine plus S-1 (NAC-GS) is recommended for patients with resectable pancreatic ductal adenocarcinoma (PDAC) in Japan. However, its real-world feasibility, the impact of treatment-related toxicity, and the influence of relative dose intensity (RDI) on outcomes remain unclear. This study evaluated the safety and efficacy of NAC-GS for resectable PDAC.

We retrospectively reviewed 117 patients with resectable PDAC who underwent treatment between January 2017 and December 2024. Outcomes were compared between patients treated with NAC-GS and those who underwent upfront surgery (UFS). Propensity score matching was performed among patients who underwent curative resection to adjust for baseline characteristics. Recurrence-free survival (RFS), overall survival (OS), recurrence patterns, adverse events, and the association between RDI and outcomes were analyzed.

The study included 46 patients in the NAC-GS group and 71 in the UFS group. Resection rates did not differ significantly between the groups. Although grade ≥3 adverse events occurred frequently in the NAC-GS group, no patient became ineligible for surgery because of treatment-related toxicity. After propensity score matching, 32 pairs were analyzed. The NAC-GS group had significantly longer RFS and OS than the UFS group. The 5-year RFS rates were 57.2% and 26.0%, respectively, and the 5-year OS rates were 60.2% and 37.2%, respectively. NAC-GS was also associated with a lower early recurrence rate. In the NAC-GS group, an RDI <70% tended to be associated with poorer survival.

NAC-GS was feasible and was associated with improved long-term outcomes and reduced early recurrence in patients with resectable PDAC. Maintaining adequate RDI may be important for maximizing its therapeutic benefit.