pproximately 60 430 new diagnoses of pancreatic cancer are anticipated in the US in 2021. 1 The incidence is rising at a rate of 0.5% to 1.0% per year, and pancreatic cancer is projected to become the second-leading cause of cancer death by 2030 in the US. 1,2 Pancreatic ductal adenocarcinoma (PDAC) accounts for the majority (90%) of pancreatic neoplasms, and the other subtypes include acinar carcinoma, pancreaticoblastoma, and neuroendocrine tumors. Most patients with pancreatic cancer present with nonspecific symptoms at an advanced stage with disease that is not amenable to curative surgery. 1 No effective screening exists. The 5-year survival rate approached 10% for the first time in 2020, compared with 5.26% in 2000. 1 The survival improvements have been modest and attributed primarily to multiagent cytotoxic therapies. [3][4][5] Recently, comprehensive germline and somatic ge-nomic sequencing became standard of care for small subgroups of patients with targeted treatment opportunities. 6,7 Olaparib, a poly (adenosine diphosphate [ADB]-ribose) polymerase inhibitor, can prolong cancer control in patients with a BRCA1/2 pathogenic germline variant. 8,9 This review summarizes current evidence regarding pathobiology, diagnosis, and management of PDAC.
MethodsA PubMed search was performed for English-language articles describing randomized clinical trials, meta-analyses, and systematic reviews of pancreatic cancer published between January 1, 2010, and July 5, 2021. We identified 43 randomized clinical trials, 85 meta-analyses, IMPORTANCE Pancreatic ductal adenocarcinoma (PDAC) is a relatively uncommon cancer, with approximately 60 430 new diagnoses expected in 2021 in the US. The incidence of PDAC is increasing by 0.5% to 1.0% per year, and it is projected to become the second-leading cause of cancer-related mortality by 2030.OBSERVATIONS Effective screening is not available for PDAC, and most patients present with locally advanced (30%-35%) or metastatic (50%-55%) disease at diagnosis. A multidisciplinary management approach is recommended. Localized pancreas cancer includes resectable, borderline resectable (localized and involving major vascular structures), and locally advanced (unresectable) disease based on the degree of arterial and venous involvement by tumor, typically of the superior mesenteric vessels. For patients with resectable disease at presentation (10%-15%), surgery followed by adjuvant chemotherapy with FOLFIRINOX (fluorouracil, irinotecan, leucovorin, oxaliplatin) represents a standard therapeutic approach with an anticipated median overall survival of 54.4 months, compared with 35 months for single-agent gemcitabine (stratified hazard ratio for death, 0.64 [95% CI, 0.48-0.86]; P = .003). Neoadjuvant systemic therapy with or without radiation followed by evaluation for surgery is an accepted treatment approach for resectable and borderline resectable disease. For patients with locally advanced and unresectable disease due to extensive vascular involvement, systemic therapy followed by radiati...