Neoadjuvant chemotherapy with gemcitabine plus S-1 (NAC-GS) is recommended in Japan for patients with resectable pancreatic ductal adenocarcinoma (resectable PDAC). The study aimed to assess the real-world feasibility of NAC-GS, examine treatment-related toxicity, and evaluate whether relative dose intensity (RDI) influences oncologic outcomes.
This was a retrospective review of 117 patients with resectable PDAC treated between January 2017 and December 2024. Patients were divided into two groups based on initial management: those who received NAC-GS (n = 46) and those who underwent upfront surgery (UFS; n = 71). Outcomes compared included resection rates, adverse events, recurrence-free survival (RFS), overall survival (OS), recurrence patterns, and the relationship between RDI and outcomes.
To reduce baseline differences between groups among patients who underwent curative resection, propensity score matching was performed. After matching, 32 pairs of patients were available for comparative survival analyses.
The full cohort comprised 46 patients in the NAC-GS arm and 71 in the UFS arm. The abstract reports that resection rates did not differ significantly between groups, indicating NAC-GS did not lead to a lower rate of proceeding to curative-intent surgery. Specific details of chemotherapy cycles, dosing schedules, and timing relative to surgery were not reported in the abstract.
Grade ≥3 adverse events occurred frequently in the NAC-GS group. Despite the frequency of these high-grade toxicities, no patient was rendered ineligible for surgery because of treatment-related toxicity. The abstract does not provide a detailed breakdown of the types or frequencies of individual adverse events or how toxicities were managed.
After propensity score matching (32 matched pairs), patients treated with NAC-GS experienced significantly longer RFS and OS compared with those who underwent UFS. Reported landmark estimates at five years were:
These findings indicate a durable survival advantage associated with neoadjuvant gemcitabine plus S-1 in the matched population.
The NAC-GS group had a lower early recurrence rate compared with the UFS group. The abstract does not specify the operational definition of "early recurrence" or provide numeric early-recurrence rates by site (local vs distant) or timing intervals.
Within the NAC-GS cohort, patients with an RDI below 70% tended to have poorer survival outcomes compared with those who maintained higher RDI. The abstract frames this as a tendency rather than a definitive statistical claim; precise hazard ratios, confidence intervals, and p-values were not reported in the abstract.
In this retrospective, single-institution–based cohort, NAC-GS was feasible in real-world practice for patients with resectable PDAC. Although high-grade toxicities were common, they did not prevent subsequent curative surgery. After matching for baseline characteristics, NAC-GS was associated with significantly improved long-term oncologic outcomes—both RFS and OS—and with a reduced rate of early recurrence.
The study highlights the potential importance of maintaining adequate relative dose intensity (RDI) during NAC-GS, as RDI <70% was associated with a trend toward worse survival. These observations support the therapeutic value of a neoadjuvant gemcitabine plus S-1 approach in this patient population and suggest dose intensity may affect benefit.
The abstract does not provide full details on several items clinicians may consider important when interpreting the results:
Because this summary is based on the abstract supplied, readers seeking comprehensive methods, full toxicity tables, and complete statistical analyses should consult the full text for those details.