Upfront surgery vs. neoadjuvant therapy for resectable pancreatic cancer: a narrative review of available evidence

Though the use of neoadjuvant therapy (NAT) is increasing in the setting of borderline resectable (BRPC) and locally advance pancreatic cancer (LAPC), the role of NAT in resectable pancreatic cancer (RPC) remains uncertain.

This is a narrative review, summarising the contemporary evidence and emerging studies comparing neoadjuvant therapy to upfront resection and adjuvant therapy in RPC.

Upfront resection followed by adjuvant chemotherapy is currently the standard of care for RPC. Though BRPC and LAPC have reported significant overall survival benefits with NAT, those results have yet to be translated to RPC. Downstaging is only reported in a small proportion of patients who receive NAT; most have stable disease and a small number have progression. Preliminary trial data have largely been consistent with that observed in the past whereby a modest improvement in R0 resection rates and pathological findings is observed with NAT, however rates of distant recurrence and overall survival remain similar to upfront resection. A significant proportion further fail to achieve resection due to the side effects, deconditioning and delays to surgery. Most international recommendations have been guided by non-randomised data sets and long-term data from emerging phase III trials are yet to be published.

Although we have observed improved R0 resection rates with NAT, this has yet to translate to a robust improvement in overall survival. Concerns regarding delays to resection, and limited response to NAT remain a topic of ongoing investigation.