Pancreatic cancer treatment: better, but a long way to go

Abstract

Remarkable progress has been made in treating pancreatic cancer over the past century, including refinement of our surgical techniques and improvements in adjuvant and neoadjuvant therapies. Despite these advances, the incidence of pancreatic cancer is rising globally, and it remains a deadly disease. In this review, we highlight the historical perspectives of pancreatic cancer treatment and outline the areas of future advancement that will assist progression towards better outcomes. Areas of future advancement include improving prevention strategies and early detection, refining our molecular understanding of pancreatic cancer, identifying more effective systemic therapies, and improving quality of life and surgical outcomes. Furthermore, systems need to be put in place to ensure all patients with pancreatic cancer receive high quality care and are given the appropriate options and sequence of therapy. This is best achieved through multidisciplinary care.

Keywords: Adjuvant therapy; Neoadjuvant therapy; Pancreatic cancer; Pancreaticoduodenectomy.

Fig. 1.. Historical timeline of the treatment of pancreatic cancer.

The first recorded attempt at a partial pancreaticoduodenectomy was by Alessandro Codivilla in Italy in 1898. Walter Kausch performed the first successful 2-stage partial pancreaticoduodenectomy in 1909. Allen Whipple was the first to perform a one-stage complete pancreaticoduodenectomy in 1942. The Gastrointestinal Tumor Study Group (GITSG) trial heralded a new era of adjuvant therapy and operative mortality fell to below 3% in the 1980s. The JASPAC 01 and PRODIGE-24 trials in the 2010s demonstrated significant improvements in median OS to over 3 years with adjuvant S-1 and adjuvant FOLFIRINOX. In 2019, PREOPANC-1 was the first phase III clinical trial to evaluate the efficacy of neoadjuvnt therapy.

Fig. 2.. Improvements in operative mortality following pancreaticoduodenectomy and median survival of patients with resectable pancreatic cancer.

Operative mortality following pancreaticoduodenectomy was over 30% at its inception and did not improve significantly until the late 1980s when it fell below 3% (dashed line) at high volume centers. The median overall survival (OS) of patients with resectable pancreatic cancer was approximately 12 months in the 1960s, leading many to question the curative intent of pancreaticoduodenectomy. Clinical trials utilizing adjuvant chemotherapy and chemoradiotherapy resulted in steady improvements in median OS with dramatic improvements to 46.5 months and 54.5 months reported from the JASPAC 01 and PRODIGE-24 trials, respectively.