Could Total Neoadjuvant Therapy Followed by Surgical Resection Be the New Standard of Care in Pancreatic Cancer? A Systematic Review and Meta-Analysis

Background. Total neoadjuvant therapy (TNT), intended as induction chemotherapy (IC) followed by radio-chemotherapy (RCT), has been taking hold in the treatment of pancreatic ductal adenocarcinoma (PDAC). The aim of this review is to summarize the available evidence on the role of TNT followed by curative surgery. Methods. Eligible studies were those reporting on patients with PDAC undergoing curative surgery after TNT. The primary endpoint was overall survival (OS). Results. A total of 1080 patients with PDAC who had undergone TNT were analyzed. The most common IC regimen was Gemcitabine (N 620, 57%). Toxicity during IC varied from 14% to 51%. Disease progression during IC varied from 3% to 25%. 607 (62%) patients underwent curative surgery after IC + CRT. In meta-analysis, the available data on lymph node metastases radicality and 2 years OS had better results in favor of TNT groups (OR 1.77, 95% CI 1.20-2.60, p = 0.004 and OR 2.03, 95% CI 1.19-3.47, p = 0.01 and OR 1.64, CI 1.09-2.47, p = 0.02, respectively). Conclusions. Despite the heterogeneity of the studies, different selection criteria, and non-negligible drop-out rate, TNT demonstrated a potential superiority to NAT without CRT in oncological and pathological outcomes, even if the main differences seem to depend on the IC regimen.