SeminarPancreatic cancer
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.
Section snippets
Epidemiology and risk factors
According to the American Cancer Society, approximately 56 000 new cases of pancreatic cancer were diagnosed in the USA in 2019 with an estimated 45 000 deaths, ranking third after lung cancer and colorectal cancer.1 It is the seventh leading cause of cancer death in both men and women worldwide, accounting for roughly 459 000 new cases and 432 000 deaths according to GLOBOCAN 2018 estimates.3 It is predicted that pancreatic cancer will soon surpass breast cancer as the third leading cause of
Histological and molecular characteristics
Most pancreatic cancers are characterised as ductal adenocarcinoma and thus represent malignancy of the exocrine pancreas whereas a minority represent neuroendocrine tumours. Most pancreatic ductal adenocarcinomas arise from precursor lesions, termed pancreatic intraepithelial neoplasias, that progress in a stepwise process through acquisition of genetic alterations and culminate in development of overt pancreatic ductal adenocarcinoma. A minority of pancreatic ductal adenocarcinoma arises from
Presentation and symptoms
Consistent with the fact that only a minority of patients diagnosed with pancreatic cancer present with surgically-resectable disease, the disease frequently causes few, if any, symptoms before it develops to the advanced stage. Unfortunately, those who do develop symptoms often have non-specific complaints—epigastric or back pain, nausea, bloating, abdominal fullness or change in stool consistency—symptoms often understandably attributed to alternative, benign causes, which can delay diagnosis.
Resectable and borderline resectable
Despite 5-year survival rates of 10–25% for patients who can undergo surgical resection, surgery remains the only treatment that offers curative potential.65, 66 Resectability status should be determined by a multidisciplinary team after evaluation with high-quality cross-sectional imaging. Tumours in the pancreatic head are typically resected with a pancreaticoduodenectomy (Whipple procedure) which includes resection of the pancreatic head, duodenum, proximal jejunum, common bile duct, gall
Future directions
Pancreatic cancer remains one of the deadliest malignancies, responsible for substantial morbidity and mortality worldwide. The sobering reality is that most patients have advanced or metastatic disease at diagnosis, and thus efforts are underway to improve early detection. As detailed in our Seminar, current guidelines recommend screening only in patients deemed high risk for developing pancreatic cancer (defined as having two or more first-degree relatives with this cancer or carrying a known
Conclusion
Pancreatic cancer remains a devastating malignancy with limited options for effective therapy. Improvement in patient outcomes will depend on multidisciplinary advances in imaging, surgical techniques, radiation, and systemic therapies. Although clinical progress has been slow, our understanding of the molecular biology of pancreatic ductal adenocarcinoma and the tumour microenvironment continues to expand and will eventually inform rational therapeutic approaches that will result in clinical
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