Resectable Pancreatic Adenocarcinoma Adjuvant vs Neoadjuvant treatment

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. Curative-intended resection and adjuvant chemotherapy represents the current standard of care.Despite substantial improvements in surgical treatment and intensified adjuvant treatment with more powerful regimens over the last years, even clearly resectable pancreatic cancer still has an unfavorable prognosis with a high risk of relapse.Neoadjuvant or perioperative multimodal therapies have substantially improved the outcome of other resectable gastrointestinal (GI) cancers such as esophagus and gastric cancer.The aggressive nature of PDAC makes it a particularly challenging disease to treat. At the time of diagnosis, approximately 9% of cases will have localized disease and 29% regional disease; but in total only 15%–20% will be deemed resectable.Neoadjuvant therapy is an emerging paradigm in pancreatic cancer care; however, its role for resectable disease remains controversial in the absence of conclusive randomized controlled trials.Postulated benefits of NAT include: identifying aggressive tumor types hence avoiding futile surgery, elimination of micrometastesis, increased R0 resection rate and increased rate of completion of multimodal treatment considering that up to 50% of patients treated in SFadj pathway fail to receive adjuvant therapy.Bayesian network meta-analysis shows that NAT for treatment of RPC is no worse than traditional SFadj approach and may even hold benefit across outcomes of: R0 resection, 1, 2, 3, 4 and 5-year survival.Three important directions for future research1) rigorous head-to-head comparison of NAT and SFadj for treatment of RPC,2) cost-effectiveness analysis of NAT versus SFadj,3) exploring methods of predictive statistical modeling to identify patients who are more likely to receive and benefit from differing treatment modalities within competing pathways.A systematic review and meta-analysis (PRISMA flow chart of search strategy and results) revealed that NAT Prolonged survival and R0 resection rates compared to surgery first approach.To this end, we await the results of the randomised, controlled, multicentre randomised phase III PREOPANC trial by the Dutch Pancreatic Cancer Group (DPCG) and further multicentre feasibility trial (ESPAC 5F) currently recruiting in the UK.