Background Elderly patients or those with poor performance status are underrepresented in clinical trials of pancreatic ductal adenocarcinoma (PDAC), and optimal treatment strategies for this frail population remain unclear. In real-world practice, gemcitabine, S-1, and stereotactic ablative radiotherapy (SABR) are used as first-line options in patients unfit for intensive combination chemotherapy. We compared these strategies in frail patients with advanced PDAC. Methods This single-center retrospective cohort study included frail patients with histologically confirmed PDAC diagnosed between February 2014 and February 2024. Frailty was defined as age ≥80 years or an Eastern Cooperative Oncology Group performance status ≥2. Patients with resectable disease were excluded. Eligible patients received first-line gemcitabine, S-1, or SABR. Overall survival (OS) was the primary endpoint. Propensity score–based overlap weighting was applied, and survival was analyzed using Kaplan–Meier methods and Cox regression. Results Among 63 patients, including 36 with metastatic disease and 27 with borderline resectable or locally advanced PDAC, median OS in metastatic PDAC was 7.70 months with gemcitabine and 4.33 months with S-1, with no significant difference after overlap weighting (HR, 1.31). In borderline resectable or locally advanced PDAC, SABR was not associated with inferior OS compared with systemic chemotherapy (HR, 1.78). Gemcitabine was associated with improved survival compared with S-1 in patients with tumor size ≥4 cm or peritoneal metastasis. Hematologic adverse events were more frequent with chemotherapy, whereas non-hematologic events were more common with SABR. Conclusions In frail patients with PDAC, gemcitabine and S-1 showed comparable survival in metastatic disease, and SABR showed no statistically significant difference in overall survival compared with systemic chemotherapy in borderline resectable or locally advanced disease, supporting individualized treatment.
Kim et al. (2026) studied this question.