Pancreatic Cancer

Precision Medicine - Biomarkers & Diagnostics

Pancreatic Cancer: An uncommon disease with few therapeutic options

According to Globocan 2018 estimates, Pancreatic Cancer representes 2.5% of all cancer cases. This disease usually causes no symptom early on, often resulting in death within a relatively short period of time. The causes and risk factors for this cancer are multiple. Since the chances of survival are low, treatments are generally aimed at slowing the development of the tumour. Progress are expected in the earlier detection of this cancer and in the development of new therapeutic approaches.

Pancreatic Cancer

About the Pancreas

The pancreas is a gland located deep in the abdomen, between the stomach and the spine. It is often described as having a head, body and tail. It is made up of 2 major components: the exocrine cells and the endocrine cells.

The pancreas produces enzymes that aid in digestion (thanks to exocrine cells) and makes insulin and other important hormones (thanks to endocrine cells) that help the body absorb sugar and control blood sugar.

What Is Pancreatic Cancer?
What are the types of Pancreatic Cancer?

Pancreatic cancer develops when cells in the pancreas grow out of control, developing a tumor. It can occurs in the head, body or tail of the pancreas.

About 95 % of pancreatic cancers are exocrine tumors, beginning in the exocrine cells of the organ. 80% of these exocrine tumors starts in the exocrine cells that line the ducts of the pancreas. Hence, these types of cancer are called pancreatic ductal adenocarcinomas.

Treatment for these tumors is based on stage of growth.

About 5% of pancreatic tumors are neuroendocrine tumors (NET), also called islet cell tumors. There are many subtypes of this type of tumor. They often grow slower than exocrine tumors, and are most often benign.

What is the incidence of Pancreatic Cancer?
How Many People Will Get Pancreatic Cancer?

The incidence of Pancreatic Cancer has markedly increased over the past decades. According to IARC (Globocan), about 485,000 individuals worldwide will be diagnosed with this condition in 2020, and this cancer will be the cause of 456,000 deaths in 2020: 131,000 people in Europe and 48,000 people in the USA.

Patients diagnosed with pancreatic cancer typically have a poor prognosis partly because the cancer usually causes no symptoms early on, leading to metastatic disease at the time of diagnosis.

Median survival from diagnosis is around 5-6 months; 5-year survival is about 5% and complete remission is still extremely rare (American Cancer Society, 2008).

Pancreatic cancer is the 12th most common cancer in the world (joint position with kidney cancer).

Pancreatic cancer is predicted to overtake breast cancer to become the third leading cause of cancer-related death in the EU.

The mortality associated with this disease is predicted to continue to increase worldwide, in some countries by as much as 120% between 2011 and 2025.

It is also important to note that Pancreatic Cancer is more common with increasing age, which is a major consideration in our modern society, and slightly more common in men than women.

What is the situation of pancreatic cancer in comparison to other cancers?

In the modern era of cancer research, Pancreatic Cancer has proven to be among the most unyielding of adversaries.

The UK charity Pancreatic Cancer Action’s impact report (2015) highlights the lack of progress being made against Pancreatic Cancer. Survival rate remains at similar levels to those seen in the 1970s (5-year survival around 5%). To compare with breast cancer (same stages III and IV), the 5-year survival rate for women is close to 72%.

By contrast, while overall cancer mortality in the UK has decreased in the past 10 years, Pancreatic Cancer mortality has increased by 8%.Across the EU, Pancreatic Cancer survival in 2017 is similar to that of the UK.

What are the causes of Pancreatic Cancer?
What are the risk factors increasing the risk of developing Pancreatic Cancer?

Cancers is often the result of one or several risk factors, even though this cancer can developed in people who don’t have any of the risk factors.

The scientific community established a list of risk factors that may increase the chances of developing a pancreatic cancer. But, as mentioned by Pancreatic Cancer UK, “it’s important to remember that having some of the risk factors doesn’t mean you will definitely get pancreatic cancer”.

The risk factors for pancreatic cancer are:
> Age (chances increase with age, most being 60+),
> Smoking,
> Obesity,
> Family history of pancreatic cancer,
> Chronic pancreatitis and hereditary pancreatitis,
> Diabetes (risk increased with long-term, 5+ years),
> Chronic, heavy alcohol use
> Diet (high in red and processed meats),
> Gender (More men are diagnosed with pancreatic cancer than women),
> Blood group (blood groups A, AB and B may have a higher risk),
> Race and ethnicity (Black people or Ashkenazi Jewish are more likely to develop pancreatic cancer).

What are the key symptoms of Pancreatic Cancer?
What are the Signs and Symptoms of Pancreatic Cancer?

Pancreatic cancer does not cause generally any signs or symptoms in the early stages. As the cancer grows, it may cause symptoms, due to the relationships of the pancreas to other organs of the digestive system.
Pancreatic cancer symptoms vary depending on its location in the pancreas: head, body or tail, and on the location of the tumor: exocrine cells or endocrine cells.

The following symptoms may indicate the development of a pancreatic cancer:
> Pain, usually in the abdomen or back,
> Unexplained Weight loss,
> Jaundice,
> Recent-onset diabetes,
> Loss of appetite,
> Indigestion,
> Nausea,
> Changes in stool,
> Pancreatitis,
> Blood clots
> Abdominal bloating or Stomach bloating.
> Fatigue, weakness and depression are also symptoms.

But all these symptoms are always associated with the development of a pancreatic cancer.

How Is Pancreatic Cancer Diagnosed?

Depending on the signs and symptoms caused by a suspicion of a pancreatic cancer, several exams and tests will be done to find the cause to make a diagnosis. If the cancer is confirmed, more tests will be done to help determine the stage (extent) of the cancer.

It is important to note that there is no standard test to diagnose pancreatic cancer, this makes its diagnostic difficult to establish.

In the current practice, Pancreatic Cancer diagnosis is usually given by a combination of clinical examination, imaging tests (computed tomography (CT) scan, magnetic resonance imaging (MRI), Positron Emission Tomography (PET) Scan, Endoscopic Retrograde Cholangiopancreatography (ERCP), endoscopic ultrasound (EUS), Laparoscopy), a blood test with Carbohydrate antigen 19-9 (CA19-9, not specific) and an invasive biopsy to get a sample of the tumor tissue to figure out the exact diagnosis.

There is no specific blood test or tumor marker to find or diagnose a pancreatic tumor.

A pancreatic exocrine tumor can cause higher bilirubin and liver enzyme levels in the blood. High levels of these substances in blood can suggest a pancreatic cancer, but these markers do not happen in all pancreatic cancer patients.

A pancreatic neuroendocrine tumors (PNETs) can be detected in measuring the following markers:
> Chromogranin A (cgA, high in most people with PNETs),
> Pancreatic polypeptide (PP, often high in people with PNETs),
> Other specific hormones made by pancreatic neuroendocrine tumors.

What are the stages of a Pancreatic Cancer?

The stage of a cancer describes how the disease has been developing, how it is serious and how best to treat it.

The earliest stage pancreas cancers are stage 0 (carcinoma in situ), and then range from stages I (1) through IV (4). In general, the lower the number, the less the cancer has spread or is difficult to treat.

 In Pancreatic Cancer, the stage of the disease is based on 3 data:
1 – The extent of the tumor (T)
2 – The spread to nearby lymph nodes (N) 3 – The spread (metastasized) to distant sites (M)

Other factors are measured to determine the prognosis of the disease:
 the tumor grade (from 1 to 3),
b) the extent of resection (from R0 to R2).

What are the main therapies to treat Pancreatic Cancer?
What Treatments exist for Pancreatic Cancer?

Standard treatments are surgery, chemotherapy, radiation, or a mix of these.

As pancreatic cancer is generally detected when tumor cells are spread over the pancreas or when the tumor is began metastatic, the decision-making model is a balance between the patient’s medical condition (side effects, patient’s preferences, and overall health) and the intrinsic characteristics of the cancer (type, spread and stage of the tumor).

The surgery option is chosen to remove the tumor or when a part of the tumor can be resected with the objective to relieve symptoms. About 20% of patients with pancreatic cancer can benefit from a surgery. Surgery is the only potentially curative treatment option in pancreatic cancer treatment.

In cancer treatment, the chemotherapy option is used to kill cancer cells or to shrink a tumor before surgery or radiation therapy.
Several chemotherapy drugs are used for pancreatic cancer: 5-fluorouracil (F-5U), Capecitabine, Gemcitabine, Nab-paclitaxel, Irinotecan, Oxaliplatin, etc., alone or in combination like: Gemcitabine + nab-paclitaxel, Gemcitabine+ Erlotinib, Folfirinox (5-flurouracil, leucovorin, irinotecan and oxaliplatin).

Here is a comparison of clinical results and the associated costs between Gemcitabine and Folfirinox treatments.

Current clinical trials study new types of treatments in the domain of immunotherapy, targeted therapy, precision medicine, etc.

What kinds of progresses are forecasted to improve the therapy efficiency and the patient quality of life during treatment?

As surgery offers today the best chance of controlling or treating pancreatic cancer, the early detection of this tumor is one of the major issues to improve treatment outcomes.

Another challenge is that pancreatic tumors are surrounded by a dense tissue layer, called the stroma. This makes it difficult for treatment to reach the tumor. Researchers are studying ways to get treatment through the stroma to make it more effective.
Also, some cancers have been successfully treated with targeted therapies which block specific mutations. But, these drugs have not been developed specifically for pancreatic cancer yet.

Molecular profiling can give information about the biology of the tumor. Results may align with targeted treatments that work well in other cancer types. As more studies are done, more targeted treatments will be developed and approved for pancreatic cancer patients whose tumors have specific molecular changes.

In their current practice of treating Pancreatic Cancer, physicians describe the situation as “a race against time”: they must quickly choose one of the available treatments, hoping it will be the most effective or the most adapted. Molecular biomarkers (and diagnostic devices) are capable to predict patient response to a particular drug regimen. This approach could help choosing the most efficient therapy or the treatment with the less side effects, with the benefit to increase the patient overall survival and its quality of life during treatment.