Pancreatic ductal adenocarcinoma, or PDAC, is the most common type of pancreatic cancer, accounting for over 90% of cases. It originates in the cells lining the ducts of the pancreas, which are small tubes that carry digestive enzymes out of the organ. These cancerous cells can multiply uncontrollably, forming a mass or tumor. The cancer can develop anywhere in the pancreas but is most frequently found in the head of the organ.
Associated Risk Factors and Symptoms
Certain factors can increase the likelihood of developing PDAC. These include:
- Chronic conditions such as long-standing type 2 diabetes and pancreatitis (chronic inflammation of the pancreas).
- Lifestyle choices, particularly smoking, with smokers being two to three times more at risk.
- Obesity.
- A family history of the disease or related genetic syndromes, such as mutations in the BRCA2 gene.
The symptoms of PDAC are often subtle and non-specific, appearing only after the tumor has grown large enough to affect surrounding organs. One of the most common indicators is jaundice, a yellowing of the skin and eyes, which occurs when a tumor in the head of the pancreas blocks the bile duct. Other signs include persistent abdominal pain that may radiate to the back, unexplained weight loss, and a loss of appetite. Digestive changes may manifest as light-colored stools and dark urine, and some individuals experience a new diagnosis of diabetes. General feelings of fatigue, weakness, and nausea are also associated with the disease.
The Diagnostic and Staging Process
Diagnosing PDAC begins with a review of symptoms and a physical exam, followed by imaging tests to visualize the pancreas. High-resolution imaging, such as a computed tomography (CT) scan, is often the first step to detect tumors and assess if the cancer has spread. Magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) may also be used. EUS is effective at identifying small tumors and allows for a guided biopsy.
While imaging provides evidence, a biopsy is required for a definitive diagnosis. During an EUS-guided procedure, a thin needle extracts a small tissue sample from the suspicious area for a pathologist to examine. The pathologist confirms the presence of cancer cells by examining the tissue under a microscope. Blood tests may also check for tumor markers like CA 19-9, though this marker is not definitive on its own.
Staging determines the extent of the cancer’s spread and guides treatment planning. The TNM system is used, assessing the tumor’s size (T), lymph node involvement (N), and whether it has metastasized (M) to distant organs. Based on these findings, the cancer is classified into stages ranging from 0 to IV. For treatment planning, doctors categorize the disease as resectable (operable), locally advanced (unresectable but not spread to distant organs), or metastatic (spread to other parts of the body).
Current Treatment Modalities
For the small percentage of patients with localized, resectable tumors, surgery offers a chance for long-term survival. The most common procedure is the pancreaticoduodenectomy, or Whipple procedure. This involves removing the head of the pancreas, part of the small intestine, the gallbladder, and the bile duct. For tumors in the body or tail of the pancreas, a distal pancreatectomy may be performed.
Chemotherapy is used in nearly all stages of PDAC. It can be given before surgery (neoadjuvant) to shrink the tumor or after surgery (adjuvant) to eliminate remaining cancer cells. For locally advanced or metastatic cancer, chemotherapy is the primary treatment. Combination regimens like FOLFIRINOX are often more effective than single-drug treatments.
Radiation therapy is often used with chemotherapy for locally advanced tumors. It uses high-energy beams to destroy cancer cells, which can shrink tumors and manage pain. This approach can sometimes shrink a tumor enough to make it operable.
Targeted therapies attack specific genetic mutations within cancer cells. Immunotherapy uses the body’s immune system to fight cancer and has shown promise in a small subset of patients whose tumors have specific molecular characteristics. These evolving therapies are part of ongoing clinical research to improve outcomes.
Understanding Prognosis and Disease Aggressiveness
The prognosis for PDAC is challenging due to late detection and the tumor’s biology. Symptoms do not appear until the disease is advanced, meaning the cancer has often spread beyond the pancreas at diagnosis. This late-stage diagnosis limits treatment options, as surgery with curative intent is only possible when the tumor is confined to the pancreas.
The tumor’s biology contributes to its aggressive behavior and treatment resistance. PDAC tumors are characterized by a dense, fibrous tissue known as stroma. This stroma makes up a large portion of the tumor mass and acts as a physical barrier. It shields cancer cells and prevents chemotherapy drugs from reaching their target effectively, creating a difficult tumor microenvironment.
The cancer cells themselves possess mechanisms that help them resist treatment and facilitate their spread. The interplay between the cancer cells and the surrounding stromal cells creates a supportive environment that promotes tumor progression. Research is focused on targeting this interaction to disrupt the protective barrier and make cancer cells more vulnerable to therapy.