Pancreatic Cancer

Epidemiology and Etiology

Pancreatic cancer is the fourth most common cause of cancer-related death in the US, with an estimated 47,050 deaths in 2020.¹ Incidence increases with age, with median age at diagnosis between 60 and 80 years.

Pathology

Pancreatic adenocarcinoma is the most common subtype. Pancreatic neuroendocrine tumors are less common, associated with a better prognosis, and are managed differently.

Clinical Presentation

Most patients present with nonspecific symptoms including asthenia, anorexia, weight loss, epigastric pain, and back pain. Tumors of the pancreatic head may present with painless jaundice. Pancreatic cancer should be considered in patients gt;50 years with abrupt-onset diabetes mellitus.

Diagnostic Testing

Patients with a suspected pancreatic tumor should undergo initial imaging with CT scan or abdominal ultrasound. However, additional imaging with a pancreatic protocol CT is often necessary to define extent of tumor involvement. Metastatic disease, if present, should be biopsied when feasible. If there is still suspicion for pancreatic cancer but the CT or ultrasound do not show a suspicious lesion, endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP) may be indicated. MRI of the liver and PET CT may also be performed for further evaluation of indeterminate liver lesions. Staging laparoscopy may be indicated in select patients with tumors in the body or tail, large tumors, or severe abdominal pain. CA19-9 levels have an 80% sensitivity and 80%-

90% specificity in symptomatic patients.

Staging

Although TNM classification is used in pancreatic cancer, clinical management is often guided by resectability of the disease.

TREATMENT

• Surgical resection is the only treatment with curative potential. The most commonly performed surgery is pancreaticoduodenectomy (Whipple procedure), which is indicated for tumors of the pancreatic head. Patients may also receive perioperative neoadjuvant or adjuvant chemotherapy. Commonly used regimens include FOLFORINOX (leucovorin, 5-FU, irinotecan, and oxaliplatin) or gemcitabine plus capecitabine.

• Patients with unresectable locally advanced or metastatic disease are treated with combination chemotherapy including FOLFORINOX, and gemcitabine plus nab-paclitaxel. Patients with germline BRCA1 or BRCA2 mutations and no progression after at least 16 weeks of platinum-based chemotherapy may benefit from maintenance therapy with the PARP inhibitor, olaparib. Pembrolizumab is effective in patients with dMMR or MSI-high. Patients with NTRK fusion positive tumors may be treated with entrectinib or larotrectinib.¹⁷