Understanding the nature of a serious disease

Pancreatic cancer (PDAC) is a type of cancer that starts in the pancreas, a small gland that sits behind the stomach and in front of the spine. It is shaped like a small banana and extends horizontally across the abdomen from the duodenum to the spleen. It is only around 10 inches in length and is divided into four regions: the head, neck, body and tail.

The pancreas plays two important roles: One in the digestion of food, its exocrine function, and two, its role in glucose regulation, an endocrine function. These functions are performed by different cell types that exist in the pancreas. The exocrine cells (ducts and exocrine glands) of the pancreas make and secrete digestive enzymes into the intestine (duodenum) to help with the digestion of food. The endocrine cells of the pancreas produce hormones such as insulin that are released into the bloodstream to add in the regulation of glucose.

Types of Pancreatic Cancer

The exocrine and endocrine compartments of the pancreas can both give rise to distinct cancers. Tumors of the endocrine pancreas, known as pancreatic neuroendocrine tumors (PNET), account for less than 2% of all pancreatic tumors. The greater majority, 95%, of cancers that arise in the pancreas are pancreatic ductal adenocarcinoma (PDAC). PDAC is usually what is meant when the term pancreatic cancer is used and is the type of cancer discussed in the remaining sections of this article.

Pancreatic cancer is considered a relatively infrequent tumor with an estimated lifetime risk of 1.5% (1 in 64).

Unfortunately, it is the third leading cause of cancer deaths in the U.S. In 2021, it is estimated that 60,430 people will be diagnosed with pancreatic cancer in this country.

Risk Factors for PDAC

The causes of pancreatic cancer are poorly understood, but studies suggest that certain genetic, lifestyle and environmental factors have been associated with increased risk.

Most pancreatic cancers are sporadic with no identifiable cause. However, several risk factors known to increase the risk of pancreatic cancer include:

1) Smoking (2x more likely)

2) Obesity (BMI> 30 are 20% more likely)

3) Chronic pancreatitis

4) Diabetes

5) Family history of pancreatic cancer

Approximately 10% of pancreatic cancer cases occur in patients with a family history of pancreatic cancer or are associated with a known genetic syndrome. Although family history is a risk factor, most pancreatic cancer is diagnosed in patients with no family history and considered sporadic.

Familial Pancreatic Cancer (FPC) is considered if there are two first-degree family members or three members of a family with pancreatic cancer. Furthermore, several inherited cancer syndromes also increase your risk for pancreatic cancer. These include known inherited mutation in a gene known to cause breast (BRCA2), colon (Lynch) and familial melanoma cancer syndrome.

These inherited cancer syndromes have been identified to increase your risk for pancreatic cancer. Talk with your doctor to determine if you should be considered for genetic testing or pancreatic cancer screening.

Is there screening and early detection for pancreatic cancer?

The majority of pancreatic cancers are found at late stages. The reason for this delay in diagnosis is multifactorial. First, pancreatic cancer has few symptoms, and if symptoms occur, they mimic more common disorders such as back pain or gallbladder disease.

Symptoms that might suggest pancreatic cancer include painless jaundice (yellow eyes and skin, dark brown urine), unexplained weight loss or new-onset diabetes in the elderly. Presently, there are no recommendations to screen people of average risk for pancreatic cancer. However, recommendation of people at high risk are presently being studied and could be offered in the right clinical context.

Diagnosis

Once suspected, pancreatic cancer is usually diagnosed by imaging, such as pancreatic protocol CT or Pancreatic MRI with MRCP. Patients will most likely undergo secondary studies such as ERCP and endoscopic ultrasound to define the cancer’s extent further and obtain a biopsy. Once a diagnosis is confirmed, patients should be seen by a multidisciplinary team in a high-volume cancer center to receive a comprehensive treatment plan. This has been shown to provide improved outcomes. Genetic testing should be considered for anyone with a new diagnosis of PDAC.

Treatment

Treatment will depend on the stage of cancer. Although there are many detailed staging systems such as AJCC. Your treatment will depend on being placed into one of four treatment groups: 1) resectable, 2) borderline resectable; 3) locally advanced; 4) distant disease. Depending on your group, your treatment may include chemotherapy, surgery, radiation therapy, immunotherapy and dietary changes.

Many patients will likely require a multimodality approach; not everyone will receive the same treatment. You and your treatment team will need to choose the best treatment regime for you and your tumor.

A multimodality approach can include chemotherapy, chemo-radiation (either before or after surgery), and surgery to achieve optimal outcomes. Surgery remains the only way to remove the tumor and offer a chance for cure. Unfortunately, approximately 20% of patients are surgical candidates. The type of surgery you require is based on the location of your tumor. Presently, if your tumor is at the head of the pancreas, you will need a pancreaticoduodenectomy (Whipple procedure). If the tumor is located in the body or tail of the pancreas, it may require a distal pancreatectomy. These procedures can be performed as a minimally invasive or open surgical approach. Operating on the pancreas requires experience and skill; the best results are achieved by a high-volume surgeon at a high-volume institution.

Survival depends on the stage of your disease. Patients with localized disease now have a five-year survival rate of 39%, while patients with regional disease have a 13% five-year survival rate.

Tomorrow’s Therapies Depend on Today’s Research

Basic and clinical research remains critically important to advance our understanding of preventing, detecting and treating pancreatic cancer. Presently, NCI-funded teams coordinate through the Pancreatic Cancer Detection Consortium (PCDC), and are trying to create blood tests to detect pancreatic cancer in the general population. Other NCI-funded researchers are trying to identify new, more effective targets and drugs to better treat patients with early and advance stage disease.

Some of the most exciting work for patients with metastatic disease is the potential to activate the immune system to identify and attack a patient’s cancer with the hope of long-term and durable effects. Because of the complex nature of pancreatic cancer, many experts believe that it is important for all patients to consider joining a clinical trial, even if they have early treatable disease.

Sarah Thayer, MD, Ph.D., FACS, is the director of Feist Weiller Cancer Center.