Neo-Adjuvant Treatment in Primary Resectable Pancreatic Cancer: A Systematic Review and PRISMA-Compliant Updated Metanalysis of Oncological Outcomes

Abstract

Background: Despite advances in treatment, the prognosis of resectable pancreatic adenocarcinoma remains poor. Neoadjuvant therapy (NAT) has gained great interest in hopes of improving survival. However, the results of available studies based on different treatment approaches, such as chemotherapy and chemoradiotherapy, showed contrasting results. The aim of this systematic review and meta-analysis is to clarify the benefit of NAT compared to upfront surgery (US) in primarily resectable pancreatic adenocarcinoma. Methods: A PRISMA literature review identified 139 studies, of which 15 were finally included in the systematic review and meta-analysis. All data from eligible articles was summarized in a systematic summary and then used for the meta-analysis. Specifically, we used HR for OS and DFS and risk estimates (odds ratios) for the R0 resection rate and the N+ rate. The risk of bias was correctly assessed according to the nature of the studies included. Results: From the pooled HRs, OS for NAT patients was better, with an HR for death of 0.80 (95% CI: 0.72–0.90) at a significance level of less than 1%. In the sub-group analysis, no difference was found between patients treated with chemoradiotherapy or chemotherapy exclusively. The meta-analysis of seven studies that reported DFS for NAT resulted in a pooled HR for progression of 0.66 (95% CI: 0.56–0.79) with a significance level of less than 1%. A significantly lower risk of positive lymph nodes (OR: 0.45; 95% CI: 0.32–0.63) and an improved R0 resection rate (OR: 1.70; 95% CI: 1.23–2.36) were also found in patients treated with NAT, despite high heterogeneity. Conclusions: NAT is associated with improved survival for patients with resectable pancreatic adenocarcinoma; however, the optimal treatment strategy has yet to be defined, and further studies are required.

Neoadjuvant and Adjuvant Chemotherapy for Pancreatic Adenocarcinoma: Literature Review and Our Experience of NAC-GS

“…Our results were in line with those of a previous meta-analysis in some respects [ 8 ] but different from those of the Prep-02/JSAP05 study, which showed a survival benefit of NAC-GS [ 25 ]. A recent meta-analysis also suggested that NAT is associated with a lower risk of development of lymph node metastasis, an improved R0 resection rate, and improved recurrence-free and overall survivals in patients with resectable disease [ 11 ]. Our negative results may be ascribed to the small number of patients, the different NAC regimens used, and the short duration of NAT.…”

“…Recently, the application of NAC has been expanded to resectable PDAC [ 11 , 23 ]. The Prep-02/JSAP05 study showed that NAC using gemcitabine plus S-1 provided significant survival benefit, while the PREOPANC study showed that NACRT using gemcitabine-based NAC and radiotherapy was associated with an improved median survival period [ 24 , 25 ].…”

“…The five-year overall survival rates were 20.5% in the test arm and 6.5% in the control arm [ 25 ]. However, the results of meta-analyses have been conflicting [ 8 , 11 ]. More recently, the effectiveness of modified FOLFIRINOX in a neoadjuvant setting has been examined [ 26 ].…”

“…On the other hand, complications associated with NATs may also preclude curative resection in potentially resectable patients, and, at present, there are no measures to predict the benefits/disadvantages of NATs. A number of excellent reviews and meta-analyses have traced the development of NAT/AT for PDAC and discussed its significance [ 8 , 9 , 10 , 11 ]. Herein, we discuss some unresolved issues associated with NAT/AT for PDAC.…”

Pancreaticoduodenectomies with Concurrent Colectomies: Indications, Technical Issues, Complications, and Oncological Outcomes

“…A recent meta-analysis of randomized studies showed statistically significantly improved negative resection margin rates and overall survival of patients with pancreatectomies for borderline resectable PDAC with neoadjuvant therapies compared with up-front surgery [94]. For resectable PDAC, another meta-analysis showed significantly higher rates of negative resection margins and negative lymph nodes after neoadjuvant therapies than upfront surgery [95]. As mentioned earlier, negative lymph nodes appear to be an important determinant of survival after PD with concurrent colectomies [39].…”