Benefit of Adjuvant Therapy After Neoadjuvant Therapy and Resection for Patients with Pancreatic Cancer: A Systematic Review and Meta-analysis

Abstract Background In recent years, neoadjuvant therapy (NAT) has received growing interest and is now the standard of care for borderline resectable (BR) pancreatic cancer (PC) and locally advanced (LA) PC. Despite the proven benefits of both NAT and adjuvant therapy (AT), a critical question remains: whether patients undergoing pancreatectomy after NAT still benefit from additional adjuvant chemotherapy. In this systematic review and meta-analysis, we aimed to answer that question and explore potential subgroups and regimens that increase or decrease a potential survival advantage. Methods A comprehensive systematic literature search was performed. The primary outcome measure was overall survival (OS), expressed as hazard ratios (HRs). HRs and their corresponding 95% confidence intervals (CIs) were collected to compare survival between patients who did and did not receive AT. The ROBINS-I-tool was used to assess the risk of bias for all included non-randomized studies. Results Overall, 29,119 patients from 30 articles with PC who underwent NAT and surgical resection with reporting of AT were included. Patients who received AT after NAT and surgical resection demonstrated a significantly longer OS, with a pooled HR of 0.85 (95% CI 0.8–0.89; p<0.0001). Patients with N0 disease gained benefit from AT, with an HR of 0.87 (95% CI 0.80–0.94; p=0.0008). AT after NAT in patients with N+ disease demonstrated an even clearer improved OS, with an HR of 0.74 (95% CI 0.65–0.85; p<0.0001). Conclusion AT after NAT and surgical resection may improve OS, especially for patients with a positive nodal status, but, importantly, also for patients with a negative nodal status. Future studies should focus on detailed reporting of chemotherapy regimens and resectability criteria.