Neoadjuvant Treatment versus Upfront Surgery for Primary Resectable Pancreatic Cancer: An Update Meta-Analysis of Comparative Studies

Abstract Background The role of neoadjuvant chemotherapy with or without radiotherapy in resectable pancreatic cancer has yet to be defined. Aims This meta-analysis aims to explore the benefit of a neoadjuvant treatment in resectable pancreatic cancer compared with upfront surgery in terms of overall survival. Methods MEDLINE, Embase and the Cochrane Library were searched for studies reporting median overall survival by intention to treat in patients with primary resectable pancreatic cancer treated with or without neoadjuvant treatment from January 2000 to December 2022. The quality assessment of the included studies was based on the Newcastle–Ottawa quality scale. Secondary outcomes included disease free survival, pathological lymph-node rate, overall and R0 resection rate. Results A total of eleven studies (seven randomized controlled trials and four cohort studies) with 9774 patients were included. Neoadjuvant treatment was found to be significantly associated to increased overall survival (p<0.001; OR: 0.82; 95% CI: 0.73–0.92) and disease-free survival (p<0.001; OR: 0.73; 95% CI: 0.59–0.89). The association of radiotherapy showed no additional benefit to chemotherapy alone in terms of overall survival in the subgroup analysis. Patients undergoing neo-adjuvant treatment were also found to be significantly associated with a higher R0 resection rate (p<0.001; OR: 1.67; 95% CI: 1.31–2.15) and negative lymph-node status (p<0.001; OR: 0.41; 95% CI: 0.26–0.64). Conclusions Neoadjuvant treatment seems to offer an advantage in terms of overall and disease-free survival in comparison to patients undergoing up-front surgery for primary resectable pancreatic cancer. Further RCTs should confirm these findings to generalize the indication of neoadjuvant treatment in this setting.