Evidence-Based Adjuvant Treatment of Resectable Pancreatic Adenocarcinoma

Abstract

Pancreatic adenocarcinoma (PAC) remains one of the most lethal cancers. The overall 5-year survival rate (all stages) remains <5%. Most people present with advanced disease and even the minority who present with resectable disease still, predominantly, die of recurrent metastatic cancer. Adjuvant treatment after surgical resection has been proposed as a method of increasing the cure rate of patients with PAC, but despite developments in new systemic and radiation treatment techniques, the optimal adjuvant therapy, according to the available evidence, is yet to be clearly defined. Adjuvant systemic chemotherapy, radiotherapy or chemoradiotherapy have all been investigated as strategies to improve locoregional and distant recurrence rates following resection of PAC. Whilst the early trials concentrated on combined modality adjuvant treatment, the large randomized controlled trials published to date have compared the various modalities and have concluded that chemoradiation therapy does not significantly improve survival, whereas adjuvant chemotherapy alone does. Despite the large numbers of patients involved in these trials, statistical and methodological flaws have lead to skepticism regarding these results. This review examines published trials of adjuvant therapy for resectable PAC, with particular emphasis on randomized studies. However, there is still ample room for further developments. Only a better understanding of the underlying biology contributing to the aggressive phenotype of PAC and the development of targeted molecular agents will finally allow significant progress to be made in the area of adjuvant therapy for resectable PAC.