Background : The benefit of neoadjuvant treatment in resectable and borderline resectable pancreatic cancer has been demonstrated through randomized controlled trials. However, the optimal neoadjuvant treatment strategy remains controversial, especially for radiotherapy.

Methods : Between 2013 and 2022, consecutive patients with resectable or borderline resectable pancreatic cancer who received 5-fluorouracil with leucovorin, oxaliplatin, and irinotecan, with or without dose modifications or gemcitabine plus nanoparticle albumin-bound paclitaxel as initial treatment following surgery were included. Patients who received radiotherapy after chemotherapy were matched 1:1 by nearest neighbor propensity scores with patients who did not receive radiotherapy. Propensity scores were measured using the tumor size at initial image, duration of neoadjuvant chemotherapy, and responsiveness to neoadjuvant chemotherapy.

Results : Of 212 patients, 166 patients were retrieved for the matched cohort. Patients who received radiotherapy after chemotherapy showed significantly better overall survival and locoregional failure-free interval than those who did not. However, there was no difference in distant metastasis-free interval between the two groups. Regarding interval between radiotherapy and surgery, short (≤ 2 weeks) or intermediate (2–4 weeks) interval was associated with lower clinically relevant pancreatic fistula rates than long (> 4 weeks) interval. In addition, the intermediate interval showed relatively lower complication rates (Clavien-Dindo grade ≥ 3A) than short or long interval.

Conclusions : In patients with resectable or borderline resectable pancreatic cancer who were scheduled for curative-intent surgery after neoadjuvant chemotherapy, additional radiotherapy was associated with better prognosis. Furthermore, if at all feasible, scheduling surgery within 4 weeks following radiation therapy could enhance the postoperative outcomes.