myTomorrows Joins in Observing World Pancreatic Cancer Day

Today is World Pancreatic Cancer Day, which is recognized each year on the third Thursday of November. This awareness campaign was launched in 2014 by the World Pancreatic Cancer Coalition, which is comprised of 95 organizations from 35 countries around the world. These organizations raise public awareness, provide patients and physicians with information and drive research into pancreatic cancer. myTomorrows is proud to lend support to these efforts aimed at preventing, diagnosing and treating this complex and deadly disease.

What is pancreatic cancer?

Pancreatic cancer is the 11th most common cancer in the world. It is also one of the deadliest and is ranked seventh globally amongst cancer-related deaths. It is more common in older patients with half the total number of patients diagnosed at age 70 or older.

The pancreas is an organ found below the stomach and liver that has the dual role of producing hormones such as insulin, as well as enzymes that aid digestion. The respective functions of the pancreas are performed by two different types of cells and therefore two different types of cancer may arise:

• Pancreatic ductal adenocarcinoma arises from cells (exocrine) that produce enzymes and is responsible for 90% of cases.
• Pancreatic neuroendocrine tumors arise from the cells of the pancreas (endocrine) responsible for hormone production.

These cancers are distinct diseases with different treatment approaches and outcomes. Pancreatic neuroendocrine tumors (PanNET) grow slowly, tend to be diagnosed earlier (in part because of abnormal hormone secretion causing noticeable symptoms) and, once treated with surgery, have a much better prognosis. The rest of this article will focus on the challenges of diagnosing and treating the commoner and far more lethal pancreatic ductal adenocarcinoma (PDAC).

What are the symptoms of pancreatic ductal adenocarcinoma?

The growth of the tumor may go unnoticed until there is a significant change in digestive function and/or obstruction of surrounding structures. Both these scenarios produce symptoms that are not specific to PDAC. Patients may complain of:

• Upper mid-abdominal pain that radiates to the back.
• Weight loss related to cancer in general or as a result of poor absorption of nutrients from the intestine (malabsorption) as there is a lack of digestive enzymes. Patients with malabsorption may also complain of greasy stools or diarrhea.
• Lack of appetite, feeling full after small meals along with nausea and vomiting, especially if the tumor is growing in such a way as to block drainage from the stomach.
• Obstructive jaundice because of a tumor blocking drainage of bile from the gallbladder causing yellow discoloration of the skin and whitening of the stool.
• Symptoms of spread beyond the pancreas to other organs (metastases) such as the stomach, liver, and lungs.

As a result of non-specific symptoms developing without PDAC being suspected, patients are often diagnosed at a late stage with locally advanced or metastatic cancer (these terms are explained later in the section on staging).

How is pancreatic ductal adenocarcinoma diagnosed?

PDAC diagnosis involves a number of different types of tests which may include imaging studies, endoscopy (with biopsy), blood tests and biomarker testing. A combination of these tests is used to confirm the diagnosis and then determine the stage of disease.

Imaging studies

Typically when patients present with symptoms an attempt is first made to visualize the tumor using ultrasound or computed tomography (CT) scan. Magnetic resonance imaging (MRI) scans may also be used. Apart from determining the location of the tumor, CT and MRI scans are also used to look for spread to other organs.

Endoscopy with biopsy

This is also a type of imaging study and can be combined with a tissue biopsy of the tumor. It involves passing a camera (scope) through the mouth, esophagus, stomach and into the small intestine in order to try to directly visualize the tumor. Endoscopic ultrasound (EUS) can be used to locate the tumor, and then a probe attached to the scope is used to obtain a tissue sample from the tumor. Endoscopic retrograde cholangiopancreatography (ERCP) is a technique whereby a probe is passed into the ducts of the liver and pancreas and a dye that is visible on X-ray is injected into them. As with the EUS, an additional probe can be used to perform a biopsy. This may not always be possible as the tumor can sometimes be located out of reach of the scope. If a tissue sample is obtained, it is examined under a microscope to confirm the diagnosis of PDAC.

Laparoscopy

Like endoscopy, this test is used to see directly inside the body. In this instance the scope is passed through the skin of the abdomen in the same way as with keyhole surgery and the surgeon examines the abdominal cavity looking for signs of the spread of PDAC to intra-abdominal organs.

Blood tests

Blood tests, such as liver function tests, may be used to assess how badly the pancreatic tumor is obstructing drainage of bile or how metastases into the liver are affecting its function. PDAC may cause levels of an enzyme called CA 19–9 to rise in the blood but this can also occur with other cancers.

Biomarker testing

Understanding of the gene mutations that cause PDAC cells to develop and grow is progressing rapidly. Biomarker testing is a process that involves examining cells to identify molecules or proteins related to gene mutations in somatic cells (i.e. gene mutations in cells that cannot be passed down from generation to generation). Genetic testing also involves cells and genes, but in this instance the test identifies gene mutations in germline cells (i.e. gene mutations in cells that are passed down from generation to generation). The science involved in these tests is complex and evolving. In broad terms, biomarker testing can be used to identify genetic subtypes in a patient who has already developed PDAC. Genetic testing may be used to identify genetic subtypes that may place the children of patients with PDAC at risk of also developing the disease. Both these tests are increasingly being used to diagnose patients and may have a bearing on treatment options.

How is the stage of pancreatic ductal adenocarcinoma determined?

The results of diagnostic tests are used to classify PDAC into stage 0, and then stages I (1) to IV (4). The numbers define how far the cancer has spread. Within the stages there are three categories that describe: the extent of the tumor (T); the spread to lymph nodes (N) and distant spread or metastasis (M). This system was devised by the American Joint Committee on Cancer (AJCC) and can be viewed in detail on the American Cancer Society (ACS) page on pancreatic cancer stages. In broad terms and in relation to treatment options, patients with PDAC can have:

• Surgically resectable cancer i.e. the whole tumor can be surgically removed (stage I and II)
• Locally advanced cancer i.e. the tumor has spread but only to nearby lymph nodes (stage III)
• Metastatic cancer i.e. the tumor has spread to other organs (stage IV)

What is the survival rate for pancreatic ductal adenocarcinoma?

Generally speaking, the survival rate for pancreatic cancer is poor. This is based on the survival rate calculated in populations. The prognosis of individual patients depends on the unique circumstances of their disease and their treatment. The ACS uses a 5-year relative survival rate which compares the likelihood of patients surviving 5 years after being diagnosed with PDAC as compared to people who do not have the disease. The 5-year relative survival rate for patients with PDAC is 9% which is why it is considered to be one of the world’s more lethal cancers.

What are pancreatic ductal adenocarcinoma treatment guidelines?

Treatment of PDAC depends on the previously described stages, the severity of symptoms, such as obstructive jaundice, as well as the patient’s general condition of health (usually referred to as “performance status”). Patients, across stages of PDAC, may opt to receive palliative care. The National Comprehensive Cancer Network (NCCN) provides the following guidance on PDAC treatment options:

Resectable disease: Surgery aimed to remove the cancer entirely. This is usually followed by chemotherapy and/or radiotherapy. If disease returns after resection, chemotherapy is recommended.

Locally advanced disease: First-line treatment is chemotherapy aimed at trying to reduce the tumor size. Chemotherapy with radiotherapy (chemoradiation) is recommended as second-line treatment for patients with good performance status.

Metastatic disease: Chemotherapy is used as first-line treatment to treat these patients. For some in whom certain mutations are present, treatment with immunotherapy — drugs that help the immune system target and kill cancer cells — may be used.

Symptomatic treatment: Across the different stages of PDAC, surgical procedures may be needed to relieve obstruction to the gallbladder and/or the small intestine. Pain care and supplemental nutrition are also often needed.

The role of clinical trials in pancreatic ductal adenocarcinoma

The National Comprehensive Cancer Network’s guidelines recommend, among others, clinical trials be considered in for patients with:

• Resectable cancer and recurrence after surgery
• Locally advanced disease and good performance status, as a potential first-line or second-line treatment option
• Metastatic disease and good performance status as a potential first-line treatment option

The European Society for Medical Oncology also counts clinical trials among its treatment recommendations for certain groups of PDAC patients. There are a number of active clinical trials investigating drugs with a variety of different targets and modes of action. Providing timely and accurate information to patients and physicians may play a role in shared decision-making that is part of the process of considering, and potentially accessing treatment options.