Focus on diagnosis and treatment of pancreatic cancer

If a doctor suspects pancreatic cancer, they will first review the patient's medical history and family medical history, then check for signs of the disease. A physical examination looks for jaundice — yellowing of the skin and eyes — as well as abnormal fluid accumulation in the abdomen, known as ascites. Blood tests check for abnormal levels of bilirubin and other substances, including CA19-9, a tumor marker that is often elevated in pancreatic cancer patients, though it can also be high in other conditions such as pancreatitis, liver cirrhosis, and obstruction of the common bile duct.

Imaging examinations help doctors determine where the cancer is located and whether it has spread. These include CT scans, PET scans, ultrasound, endoscopic ultrasound (EUS), endoscopic retrograde cholangiopancreatography (ERCP), and percutaneous transhepatic cholangiography (PTC). Tissue examination through fine needle aspiration (FNA) may also be performed, along with molecular detection of the tumor to identify biomarkers — specific proteins and genes — that can help guide treatment decisions.

Pancreatic cancer is commonly staged based on whether it can be surgically removed and how far it has spread. Resectable pancreatic cancer can be surgically removed, with the tumor confined to the pancreas or extending slightly beyond it but not reaching major arteries or veins. Only about 10% to 15% of patients are at this stage at diagnosis. Border resectable pancreatic cancer may be difficult to remove initially, but after chemotherapy and/or radiation therapy to shrink the tumor, surgical removal may become possible.

Locally advanced pancreatic cancer has grown into a nearby artery, vein, or organ and cannot be surgically removed, though it has not spread to distant parts of the body. Approximately 35% to 40% of patients are at this stage when diagnosed. Metastatic pancreatic cancer has spread beyond the pancreas to distant organs such as the liver, and accounts for about 45% to 55% of diagnoses. For patients who are surgical candidates, doctors also use the TNM staging system, ranging from Stage 0 (carcinoma in situ) through Stage IV (cancer spread to other parts of the body).

Surgery aims to remove all cancerous tissue with clean margins, meaning no cancer cells remain at the edges of the removed tissue. However, only about 20% of pancreatic cancer patients are eligible for surgery, as most cases have already spread by the time of diagnosis. Surgical options include the Whipple operation for cancer in the head of the pancreas, distal pancreatectomy for cancer in the tail, and total pancreatectomy when cancer has spread throughout the organ. Surgery may be combined with radiation therapy and/or chemotherapy — given after surgery as adjuvant therapy, or before surgery as neoadjuvant therapy to shrink the tumor.

Radiation therapy uses high-energy x-rays or particles to destroy cancer cells, with external radiation therapy being the most common type. Traditional radiation therapy is delivered in lower daily doses over 5 to 6 weeks, while stereotactic radiotherapy (SBRT or CyberKnife) delivers higher doses over a shorter period of about 5 days. Chemotherapy is often used alongside radiation to enhance its effects. FDA-approved chemotherapy drugs for pancreatic cancer include gemcitabine, fluorouracil (5-FU), paclitaxel, capecitabine, oxaliplatin, irinotecan, and others. First-line chemotherapy regimens for locally advanced or metastatic disease include FOLFIRINOX and gemcitabine plus paclitaxel, with second-line options available for patients whose disease progresses or who experience intolerable side effects.

Targeted therapy focuses on specific genes, proteins, or tissue environments that drive cancer growth. Erlotinib, which blocks the epidermal growth factor receptor (EGFR), is currently the only FDA-approved targeted therapy for pancreatic cancer, used in combination with gemcitabine. Tumor genetic testing helps identify the most effective targeted treatments for individual patients, and research into other targeted agents — including those addressing the commonly mutated Ras gene — is ongoing.

Immunotherapy seeks to enhance the body's natural defenses against cancer. Cancer vaccines, immune checkpoint inhibitors (such as PD-1 and CTLA-4 antibodies), and adoptive immunotherapy involving genetically modified T cells are all being studied. While checkpoint inhibitors have shown limited effectiveness for most pancreatic cancer patients, they may benefit a small subset with specific genetic mutations. Gene therapy, which delivers corrective genes to cancer cells using specially designed viruses, is another area of active investigation. Additionally, research into cancer stem cells — which may be particularly resistant to treatment — and newer chemotherapy formulations such as nanoliposome irinotecan continue to expand the options available for patients with advanced pancreatic cancer.