Most pancreatic cancers are exocrine tumors, typically adenocarcinomas, with only 7% (https://www.pancan.org/facing-pancreatic-cancer/about-pancreatic-cancer) being neuroendocrine tumors. Overall survival depends on many factors, including stage and type. Five-year survival rates for localized disease are about 37%, but overall survival (https://www.cancer.org/cancer/pancreatic-cancer.html) for all stages is only 9%. Approximately one-third (https://www.cancer.gov/types/pancreatic/hp/pancreatic-treatment-pdq) of patients with pancreatic cancer present with locally advanced disease.

Risk Factors and Presentation

Individuals with a personal history of smoking, diabetes, pancreatitis, older age, obesity, African American or Ashkenazi Jewish ethnicity, or family history of pancreatic cancer are at higher risk to develop pancreatic cancer (NCI, 2020). Initial presenting symptoms may be vague but include abdominal pain, jaundice, anorexia, nausea, light-colored stools, tea-colored urine, or pancreatitis (NCI, 2020). Patients may also present with ascites or thrombosis.

Diagnostic studies typically include (https://www.pancan.org/facing-pancreatic-cancer/about-pancreatic-cancer) imaging such as computed tomography, magnetic resonance imaging, or endoscopic ultrasound. Endoscopic retrograde cholangiopancreatography may be indicated (https://www.cancer.org/cancer/pancreatic-cancer.html) to visualize disease, obtain biopsy, or place a stent if the disease is obstructing the bile or pancreatic duct. Elevated liver function tests and biomarkers (e.g., CA19-9, carcinoembryonic antigen) can sometimes aid in disease assessment. Germline testing is recommended (https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf) in patients with confirmed diagnoses to assess for hereditary cancer syndromes.

Biomarkers

Germline variants associated with hereditary susceptibility to developing pancreatic and other cancers may occur in the APC, ATM, BRCA1, BRCA2, CDK4, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, TP53, and VHL genes. BRCA2 pathogenic variants account for 5%–17% (https://voice.ons.org/www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf) of hereditary pancreatic cancers; those patients should be referred for genetics professionals for counseling. Identifying families who carry a pathogenic variant enables them to make decisions about intensive prevention and screening.

BRCA1, BRCA2, and PALB2 may predict response (https://doi.org/10.4081/oncol.2019.410) to platinum-based treatments and are predictive of response to PARP inhibitors. CA 19-9 is the only approved (http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5883088) biomarker for monitoring response to treatment. If patients present with metastatic disease, somatic testing should focus on actionable variants and may include ALK, NRG1, NTRK, or ROS1 fusions, BRAF, BRACA1/2, HER2, KRAS, PALB2 variants, and mismatch repair (MMR) deficiency. Cell-free DNA testing through liquid biopsy can be considered (https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf) if tumor tissue testing is not possible.

Treatment

Treatment options depend on the cancer’s type and stage. General surgery with the complex whipple or other procedures is standard for resectable disease. Most of the time, pancreatic cancer requires additional chemotherapy or radiation. Systemic therapy is a part of the treatment plan for pancreatic cancer in any stage and can be given adjuvantly, first-line, subsequently, or palliatively. Chemotherapy or radiation may also be given neoadjuvantly to improve surgical options for unresectable advanced disease.

Chemotherapy options include gemcitabine, FOLFIRINOX, abraxane, capecitabine, or others. Targeted agents (e.g., erlotinib) may be indicated for advanced disease. NTRK gene fusion-positive disease may respond to (https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf) larotrectinib or entrectinib and germline BRCA1 or BRCA2 variants to olaparaib. If patients' tumors are MSI-H or MMR deficient, they may respond to a PD-L1 inhibitor. Ablation and embolization treatment may be used (https://www.cancer.org/cancer/pancreatic-cancer.html) palliatively. Clinical trial options should be reviewed.

Side Effects and Toxicities

Local and systemic therapies can cause a variety of physical and psychosocial effects. Side effects from surgery include (https://doi.org/10.1188/18.ONF.E36-E52) postoperative or chronic pain, fatigue, poor appetite, infection, bleeding, or weight. Patients may experience (https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf) difficulty with digesting foods and require pancreatic enzyme replacement to aid with malabsorption. Radiation may lead to skin irritation, nausea or vomiting, diarrhea, stomatitis, fatigue, and other side effects. Systemic chemotherapy can cause (https://doi.org/10.1188/15.cjon.751-757) nausea or vomiting, myelosuppression, diarrhea or constipation, hair loss, peripheral neuropathy, and fatigue.

Targeted agents have unique side effects and toxicity risks that must be routinely monitored after reviewing the package insert or other drug reference resources. Identifying toxicities and adjusting therapies is critical to keeping patients on treatment and improving outcomes.

Survivorship

Long-term side effects (https://doi.org/10.1188/18.ONF.E36-E52) from surgery, radiation, and systemic therapy can cause prolonged symptoms and must be assessed regularly. Biliary obstruction may require stenting or drainage. Tumor-related pain is not uncommon, and appropriate analgesic management is critical. Palliative radiation or nerve blocks may be useful in some situations.

Patients must also be screened for distress, depression, anxiety, and other psychosocial effects and referred to other providers as indicated. Early referral to palliative care is important (https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf) to help to manage symptoms and improve quality of life.