Pancreatic cancer

Summary

Pancreatic cancer is a highly fatal disease with a 5-year survival rate of approximately 10% in the USA, and it is becoming an increasingly common cause of cancer mortality. Risk factors for developing pancreatic cancer include family history, obesity, type 2 diabetes, and tobacco use. Patients typically present with advanced disease due to lack of or vague symptoms when the cancer is still localised. High quality computed tomography with intravenous contrast using a dual phase pancreatic protocol is typically the best method to detect a pancreatic tumour and to determine surgical resectability. Endoscopic ultrasound is an increasingly used complementary staging modality which also allows for diagnostic confirmation when combined with fine needle aspiration. Patients with pancreatic cancer are often divided into one of four categories based on extent of disease: resectable, borderline resectable, locally advanced, and metastatic; patient condition is also an important consideration. Surgical resection represents the only chance for cure, and advancements in adjuvant chemotherapy have improved long-term outcomes in these patients. Systemic chemotherapy combinations including FOLFIRINOX (5-fluorouracil, folinic acid [leucovorin], irinotecan, and oxaliplatin) and gemcitabine plus nab-paclitaxel remain the mainstay of treatment for patients with advanced disease. Data on the benefit of PARP inhibition as maintenance therapy in patients with germline BRCA1 or BRACA2 mutations might prove to be a harbinger of advancement in targeted therapy. Additional research efforts are focusing on modulating the pancreatic tumour microenvironment to enhance the efficacy of the immunotherapeutic strategies.

Introduction

Pancreatic cancer remains a highly fatal malignancy and is projected to become the second leading cause of cancer death in the USA in the next twenty to thirty years. The 5-year survival rate at the time of diagnosis is 10% in the USA, as approximately 80–85% of patients present with either unresectable or metastatic disease.1, 2 Even for the small subset of patients who are diagnosed with a localised, resectable tumour, the prognosis remains poor with only 20% surviving 5 years following surgery. Over the past decade, advances in diagnostic approaches, perioperative management, radiotherapy techniques, and systemic therapies for advanced disease have made relevant but only modest incremental progress in patient outcomes. New strategies for screening high-risk patients to detect pancreatic tumours at earlier stages are desperately needed to make a clinically significant impact. In this Seminar, we discuss the latest developments in pancreatic cancer with respect to epidemiology and risk factors, pathology, diagnosis, and treatment, and we conclude with future directions in the field over the next several years.