Neoadjuvant Chemotherapy With or Without Radiotherapy in Resected Pancreatic Ductal Adenocarcinoma

Importance: The role of preoperative radiotherapy after neoadjuvant chemotherapy for pancreatic cancer remains controversial. Objective: To evaluate whether the addition of radiotherapy to chemotherapy is associated with improved oncologic outcomes in patients undergoing resection for pancreatic cancer. Design, Setting, and Participants: This was a retrospective propensity score-matched cohort study of patients undergoing pancreatic cancer resection between 2015 and 2023, with a median follow-up of 44 months. Patients were recruited from 2 high-volume referral centers. Of patients undergoing pancreatectomy after neoadjuvant treatment for pancreatic ductal adenocarcinoma, those treated with fluorouracil, leucovorin, irinotecan, and oxaliplatin or gemcitabine/nab-paclitaxel with or without preoperative radiation met eligibility criteria. Patients with metastatic disease, surgery-related mortality, or follow-up less than 12 months were excluded. Treatment groups were matched 1:1 on age, sex, comorbidity, tumor characteristics, baseline carbohydrate antigen 19-9 level, resectability status, and chemotherapy exposure. Exposure: Neoadjuvant chemotherapy with or without radiotherapy. Main Outcomes and Measures: Event-free survival, pattern of recurrence, and overall survival. Results: Of 1201 consecutive patients undergoing pancreatectomy after neoadjuvant treatment for pancreatic ductal adenocarcinoma, 869 met eligibility criteria. Among 800 included patients (median [IQR] age, 65 [58-71] years; 402 men [50.2%]), 438 received neoadjuvant chemotherapy and radiotherapy and 362 chemotherapy alone. After matching, 226 patients per group were analyzed; most had resectable (117 of 226 [51.1%]) or borderline-resectable (104 of 226 [46.5%]) disease. Radiotherapy was associated with higher rates of pathologic complete response (15 of 226 [6.6%] vs 10 of 226 [4.4%]), node-negative disease (139 of 226 [61.5%] vs 76 of 226 [33.6%]), and R0 resection (192 of 226 [85.0%] vs 118 of 226 [52.2%]). Recurrence patterns were similar, with distant recurrence as the predominant first site of failure in both groups (116 of 226 [51.3%] vs 109 of 226 [48.3%]). In competing risk analysis, the cumulative incidence of locoregional recurrence did not differ (subdistribution hazard ratio [HR], 0.90; 95% CI, 0.53-1.54; P = .71). Radiotherapy was not associated with improved event-free survival (HR, 1.10; 95% CI, 0.88-1.37; P = .38) or overall survival (HR, 1.02; 95% CI, 0.79-1.32; P = .84). Conclusions and Relevance: Results of this cohort study suggest that although the addition of radiotherapy to neoadjuvant chemotherapy was associated with an improved pathologic response, it was not associated with survival benefit or reduced recurrence in resectable and borderline-resectable pancreatic cancer. These findings highlight the limited impact of locoregional control in a disease driven by systemic progression.