Carcinoma of the Pancreas
Summary of Key Points
• Pancreatic adenocarcinoma is the tenth leading cause of cancer in the United States, but the fourth leading cause of cancer-related deaths.
• The overall 5-year survival for all patients is <5%: 15% to 20% of patients present with resectable/ borderline resectable disease with median survival of 20 to 24 months; 25% to 30% present with locally advanced/unresectable with median survival of 8 to 14 months; 50% to 60% present with metastatic disease with median survival of 4 to 6 months.
• Familial atypical multiple-mole melanoma syndrome, hereditary pancreatitis, Peutz-Jeghers syndrome, and a strong family history of pancreatic cancer are the strongest risk factors and these patients should undergo screening. Risk factors also include smoking, heavy alcohol consumption, chronic pancreatitis, obesity and diabetes.
• Screening of the general population is not indicated at this time.
• Mutations in the KRAS oncogene and the CDKN2A tumor suppressor gene are found in more than 80% of pancreatic tumors and are thought to be early mutations. Inactivation of tumor suppressor genes TP53 and SMAD4 are thought to occur later in the tumorigenesis process.
• Pancreatic intraepithelial neoplasms (PanINs) are microscopic precursor lesions. PanIN-3 lesions should be fully resected when found. Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are noninflammatory cysts that can lead to pancreatic cancer. All MCNs, main duct IPMNs, and symptomatic branch duct IPMNs should be resected.
• Jaundice, abdominal pain, malabsorption, weight loss, back pain, and nausea/vomiting are common manifesting symptoms.
• Pancreatic protocol computed tomography (or magnetic resonance imaging) should be used for diagnosing and staging. Endoscopic ultrasound may offer additional staging information. It is critical to determine resectability on imaging as that will determine the course of treatment.
• All patients should be evaluated in a multidisciplinary setting when possible.
• Surgery should be considered upfront in patients with resectable disease unless treated on a neoadjuvant clinical trial.
• Patients should receive adjuvant 5-FU– or gemcitabine-based chemotherapy with 5-FU– or gemcitabine-based chemoradiation when appropriate as adjuvant therapy leads to longer survivals.
• Neoadjuvant chemotherapy followed by chemoradiation can be given in patients with borderline resectable disease to increase the likelihood of R0 resections, treat micrometastatic disease earlier, and avoid surgery in patients who demonstrate early progression.
• Locally advanced and metastatic disease patients can be treated with the same systemic chemotherapy regimens. Approved regimens include gemcitabine single-agent therapy, gemcitabine combination therapy, and 5-FU combination therapy.
• Chemoradiation or stereotactic body radiotherapy can be considered for locally advanced patients with good performance status if there is no disease progression after initial systemic chemotherapy.
• Palliative measures should be introduced early for advanced patients and focus on relieving pain, biliary obstruction, gastric outlet obstruction, and malnutrition.
• Additional studies are needed to evaluate the ability of novel biomarkers to guide pancreatic cancer management.
