Abstract
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.
Highlights
Introduction iationsPancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer mortality in developed countries and one of the most lethal malignant neoplasms across the world [1]
2911 relevant non-duplicated records were identified; 2892 of them were excluded based on the title or the abstract because they covered a variety of irrelevant topics
This is the first systematic review investigating the role of Total neoadjuvant therapy (TNT) and surgery with curative intent in pancreatic ductal adenocarcinoma (PDAC), with a comparison to Neoadjuvant chemotherapy (NAT) without CRT
Summary
Introduction iationsPancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer mortality in developed countries and one of the most lethal malignant neoplasms across the world [1]. Surgical resection in combination with adjuvant systemic chemotherapy is still the standard of care with curative intent [2,3]. At diagnosis, only 15–20% of patients are resectable and about 30% have locally advanced unresectable tumors and are generally given palliative measures only [4,5,6]. Neoadjuvant chemotherapy (NAT) is increasingly administered to borderline-resectable (BR) and locally advanced (LA) PDAC with the achievement of a higher percentage of resectability and improvement of oncological outcomes [7,8]. The concept of neoadjuvant rather than adjuvant treatment in PDAC is attractive for several reasons: downstaging of large tumors to allow margin negative resections, facilitate improved patient selection for Licensee MDPI, Basel, Switzerland.
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