Background: Only 15-20% of patients with pancreatic ductal adenocarcinoma (PDAC) have a resectable tumor at the time of diagnosis. Effective multimodal treatment concepts including neoadjuvant chemotherapy are therefore needed. Following upfront resection, adjuvant chemotherapy has become mandatory to prevent early tumor recurrence.
Purpose: The aim of this article was to summarize existing evidence on neoadjuvant and adjuvant chemotherapy in PDAC with a focus on high-level evidence based on randomized controlled phase III clinical trials.
Results and conclusions: Neoadjuvant chemotherapy represents an emerging concept for borderline resectable and locally advanced PDAC. To date, randomized trials have failed to provide proof-of-concept outcomes, mostly because of failure to achieve recruitment targets. Nevertheless, this approach needs to be further evaluated scientifically as recent data from a large single-arm cohort study showed that neoadjuvant multimodal therapy could achieve a resection rate in the order of 60% of patients with locally advanced PDAC. For patients with a primarily resectable tumor, however, study results remain unconvincing, and therefore, neoadjuvant therapy should not be used routinely outside of a clinical trial. Adjuvant chemotherapy with gemcitabine and capecitabine in unselected patients can double 5-year overall survival to around 30% compared to mono-chemotherapy with either 5-fluorouracil with folinic acid or gemcitabine. In selected patients, adjuvant modified FOLFIRINOX can produce a 5-year survival rate of around 50%. Further potential gains are to be made in the selection of patients for particular therapies based on the transcriptomic and genetic signature of individual tumors.
Keywords: Adjuvant chemotherapy; Evidence-based medicine; Neoadjuvant chemotherapy; Pancreatic cancer; Precision medicine; Transcriptomics.