Ductal Adenocarcinoma of Pancreas

Pancreatic ductal adenocarcinoma is the most common and deadliest form of pancreatic cancer, affecting thousands of people each year. Understanding this disease, its symptoms, and treatment options can help patients and their families navigate the difficult journey ahead.

Table of contents

• What is Pancreatic Ductal Adenocarcinoma?
• How Common is This Cancer?
• Signs and Symptoms
• Risk Factors
• Diagnosis and Testing
• Treatment Options
• Outlook and Survival
• Living with Pancreatic Ductal Adenocarcinoma

What is Pancreatic Ductal Adenocarcinoma?

Pancreatic ductal adenocarcinoma, often called PDAC, is a type of cancer that begins in the cells that line the small tubes, or ducts, inside the pancreas^[1]. These ducts normally carry digestive juices containing enzymes (special proteins that help break down food) from the pancreas into the small intestine^[4].

• Pancreas
• Pancreatic ducts
• Small intestine

The pancreas is a small gland, about 6 inches long, that sits behind the stomach. It has three main parts: the head (wider end), the body (middle section), and the tail (narrow end)^[11]. This gland performs two important jobs: it makes digestive juices that help break down food, and it produces hormones like insulin and glucagon that help control blood sugar levels^[11].

PDAC is a type of exocrine cancer, meaning it develops from the cells that form the ducts and glands of the pancreas^[5]. It can grow anywhere in the pancreas, though it most often appears in the head of the pancreas^[3].

How Common is This Cancer?

Pancreatic ductal adenocarcinoma is the most common type of pancreatic cancer, making up more than 80% to 90% of all cases^[4][5]. About 95 out of 100 (95%) of all pancreatic cancers are exocrine cancers, and most of these are PDAC^[3].

This disease is the fourth most common cause of cancer-related deaths worldwide^[4]. In 2012, around 44,000 new cases were diagnosed in the United States alone, with more than 37,000 deaths from the disease, affecting both men and women^[4]. The number of cases is expected to rise in the future, with projections showing a more than two-fold increase within the next ten years^[6].

Pancreatic cancer rarely occurs before the age of 40, and more than half of cases happen in people over 70 years old^[12].

Signs and Symptoms

Unfortunately, pancreatic ductal adenocarcinoma does not usually cause symptoms in the early stages^[1][8]. Early-stage tumors don’t show up on imaging tests, which is why many people don’t receive a diagnosis until the cancer has spread to other parts of the body^[8]. This late detection makes the disease particularly difficult to treat.

As the cancer grows and begins to affect other organs in the digestive system, symptoms may start to appear. Common signs and symptoms include^[3][7][8]:

• Jaundice (yellowing of the skin and the whites of the eyes), which happens when the cancer blocks the bile duct
• Pain in the upper abdomen or stomach area that may spread to the back
• Unexplained weight loss
• Loss of appetite
• Light-colored or clay-colored bowel movements
• Dark-colored urine
• Itchy skin
• Nausea and vomiting
• Fatigue (extreme tiredness)
• Gas or bloating
• Swollen gallbladder
• Blood clots
• New-onset diabetes (high blood sugar that develops suddenly)

Some people develop vague symptoms up to one year before they receive a diagnosis^[8]. Many people report that their first symptoms were back pain or stomach pain. These symptoms can come and go at first, but may get worse after meals or when lying down^[8].

A doctor might suspect pancreatic cancer if a patient has recently developed diabetes or pancreatitis (a painful condition caused by inflammation in the pancreas)^[8].

Risk Factors

While the exact cause of pancreatic ductal adenocarcinoma is not fully understood, several risk factors increase the chance of developing this disease^[11]:

Tobacco smoking is a major risk factor. People who smoke are two times more likely to develop pancreatic cancer compared to those who have never smoked. About 20-35% of pancreatic cancers are caused by cigarette smoking^[7]. About 25% of cases are linked to smoking^[12].

Obesity and being overweight also increase risk. About 20% of obese people have an increased risk of developing pancreatic cancer, and the risk is even higher in people who have been obese since childhood^[7].

Diabetes is another important risk factor. Having diabetes increases the chances of developing this cancer^[11]. The connection between diabetes, obesity, and type 2 diabetes is particularly concerning, as these are emerging public health challenges^[6].

Other risk factors include^[11][12]:

• A family history of pancreatic cancer
• History of chronic pancreatitis (long-term inflammation of the pancreas)
• Certain rare genetic conditions, such as hereditary breast and ovarian cancer syndrome, Lynch syndrome, familial atypical multiple mole melanoma syndrome, and ataxia-telangiectasia
• Alcohol abuse
• Tobacco abuse (including cigars and other forms)

The specific combination of smoking, diabetes, and poor diet increases the risk of pancreatic cancer the most beyond any one factor alone^[1].

For a small group of approximately 5-6% of all PDAC patients, genetic factors such as germline mutations (inherited changes in genes) in BRCA1/2, ATM, MLH1, TP53, or CDKN2A represent additional risk factors^[6].

Life style habits, including alcohol and tobacco abuse, which are well-known to increase the risk for several other types of cancer, also appear to be involved in PDAC development^[6].

Diagnosis and Testing

Pancreatic cancer is difficult to diagnose early because it typically doesn’t cause symptoms until it has reached an advanced stage^[11]. Early-stage pancreatic tumors don’t show up on imaging tests^[8].

Tests that examine the pancreas are used to diagnose and determine the stage of pancreatic cancer^[11]. These may include:

• Medical imaging tests such as CT scans (computed tomography), MRI scans (magnetic resonance imaging), and ultrasound to create pictures of the inside of the body^[5]
• Blood tests to check for certain markers or substances that might indicate cancer^[5]
• Tissue biopsy, where a small sample of tissue is removed and examined under a microscope to look for cancer cells^[5]
• Endoscopy procedures to look inside the digestive tract

A particular challenge for diagnosing PDAC is that pancreatic tumors contain a relatively low percentage of cancerous cells compared to normal or surrounding tissue^[4]. This makes it harder to get clear results from tests.

Some people decide to get a second opinion after receiving a diagnosis^[11]. Regular checkups can be important, especially for people with risk factors, as they may show subtle signs on bloodwork or a medical exam^[5].

Treatment Options

How well pancreatic ductal adenocarcinoma responds to treatment depends largely on the stage of disease at the time of diagnosis^[6]. Only 10-20% of PDAC patients have cancer that can be surgically removed at diagnosis, while the remaining 80-90% have locally advanced, non-removable stages or distant metastases (cancer that has spread to other parts of the body)^[6].

Surgery followed by chemotherapy is the only possibly curative therapy available^[6]. Surgery aims to remove the cancerous part of the pancreas. However, metastatic pancreatic cancer is not curable and cannot be completely removed by surgery^[7].

Chemotherapy uses drugs to kill cancer cells. It is commonly employed as first-line treatment in patients with non-resectable or borderline-resectable tumors^[6]. Common chemotherapy drugs include:

• Gemcitabine and capecitabine (nucleoside analogues)
• 5-fluorouracil or 5-FU (a pyrimidine analogue)
• FOLFIRINOX, a combination of folinic acid, 5-FU, irinotecan, and oxaliplatin, which has been reported to nearly double median survival in the metastasized stage compared to gemcitabine alone^[6]
• The combination of gemcitabine and nab-paclitaxel (nanoparticle albumin-bound paclitaxel), which has shown significant improvement in overall survival^[6]

However, these more intensive protocols are associated with higher toxicity, often preventing their use in elderly patients or those with poor overall health^[6].

Radiation therapy (also called radiotherapy) uses high-speed energy to kill cancer cells^[7]. Radio(chemo)therapy has been rather infrequently used for treating PDAC, since the majority of patients have disseminated stages where local treatment is of secondary importance^[6]. However, neoadjuvant radiotherapy (radiation given before surgery) has the potential to improve PDAC resectability in some cases^[6].

Immunotherapy activates or suppresses the immune system to fight cancer^[7]. Targeted therapy uses drugs directed at blocking certain genes or proteins^[7]. Research showed that 42% of tumors studied had a genomic alteration that may qualify for a current clinical trial^[4].

Supportive (palliative) care may help control symptoms and side effects caused by the disease and treatments, and can impact quality of life^[5].

Outlook and Survival

Pancreatic ductal adenocarcinoma is one of the deadliest forms of cancer^[5]. The disease is almost always fatal^[4]. The 5-year overall survival rate is less than 8%^[6]. Five-year survival rates are around 8%, though some sources indicate even lower rates^[5].

Late detection and a particularly aggressive biology are the major challenges which determine therapeutic failure^[6]. Because most pancreatic cancers are not found until advanced stages, the outlook is poor^[5].

However, survival rates are constantly changing with new treatments, and the main factor determining survival is whether it is possible to surgically remove the cancer^[5]. Certain factors affect prognosis (chance of recovery) and treatment options^[11].

A person with PDAC should discuss the outlook with their doctor because each case varies^[5]. A variety of treatment options can slow the disease, reduce pain, and in less common cases, cure the cancer in its early stages^[5].

Metastatic pancreatic cancer is defined as Stage 4 pancreatic cancer and is not curable^[7].

Living with Pancreatic Ductal Adenocarcinoma

A diagnosis of pancreatic cancer requires a patient to adapt to many life changes. The disease brings a wide range of new emotions, various physical symptoms, and numerous decisions regarding care^[18].

Developing a strong support system is crucial. This includes family, friends, clergy, and a good medical team. A support network will help patients deal with different aspects of pancreatic cancer^[18]. Patients may find comfort in talking to their support network about emotions and physical feelings on a day-to-day basis. They may also need help with practical aspects of house chores and daily living during periods of care^[18].

Connecting with others who have been in similar situations can be valuable. This can happen through one-on-one connections or support groups. Other patients can often validate feelings, share experiences, and provide companionship^[18].

Dietary needs will change. Resources are available to help patients adjust to these changes and better understand nutritional needs^[5]. Eating healthy and maintaining a healthy weight may help. A balanced diet that includes a variety of fruits and vegetables, choosing whole grains over processed grains, and limiting or avoiding intake of red and processed meats, alcohol consumption, and reducing intake of sugary and high-fat foods is recommended^[17].

Staying physically active can be beneficial. Regular exercise has many benefits for those with pancreatic cancer, including improved mood, energy levels, and overall physical health. Types of exercise recommended include walking, swimming, and yoga. Gradually incorporating exercise into a daily routine can help to build strength and endurance^[17]. Aim for at least 30 minutes of physical activity per day^[17].

Quitting smoking can have many benefits, including reducing the risk of cancer recurrence. Strategies to quit smoking include nicotine replacement therapy, counseling, and support groups^[17].

Managing stress is important, as stress can have a negative impact on cancer treatment. Techniques for stress management such as meditation, deep breathing, and yoga can help to reduce stress and improve overall well-being^[17].

Self-care should be a priority. This includes enjoying the little things and taking time to do things you enjoy. You may need to adapt an activity, but it doesn’t mean activities are impossible. A change in life events can also spark interest in new hobbies and pursuits. Consider journaling, meditation, yoga and other relaxation exercises, as well as social activities in the community^[5].

Maintaining a positive outlook can be difficult but important. Staying positive and hoping for the best can push a patient to continue battling the disease and follow medical advice. A positive outlook can help a patient take better care of themselves and appreciate meaningful things in the present^[18].

Regular follow-up appointments are important. Monitoring for recurrence is essential for early detection and treatment^[17].

Remember that you are not your cancer. Even though you have the disease, you get to decide how you want to live the rest of your life. You can choose to live with hope^[16].

It is important to recognize when you need additional support. If you’re feeling consistently overwhelmed, anxious, or depressed, it may be time to speak with a healthcare professional. Mental health care is an important part of cancer recovery^[17].