Patient education: Pancreatic cancer (Beyond the Basics)

INTRODUCTION — The pancreas is an organ that is located behind the stomach (figure 1). It has two main functions:

●Making hormones, including those that regulate blood glucose (sugar) levels ("endocrine" function)

●Producing digestive juices that help the body break down food ("exocrine" function)

Pancreatic cancer is one of the leading causes of cancer-related death in the United States. Two types of cancer can affect the pancreas:

●Pancreatic ductal adenocarcinoma – The most common type is cancer of the exocrine pancreas that originates in the pancreatic ducts (figure 1). The ducts are responsible for carrying pancreatic digestive juice to the intestines. This type of pancreatic cancer, called "pancreatic ductal adenocarcinoma," is discussed in this article.

●Pancreatic neuroendocrine tumors – Another type of cancer consists of a group of tumors that originate from the cells that make hormones such as insulin. These tumors are called "pancreatic neuroendocrine tumors" and are not discussed in this article.

More detailed information about pancreatic cancer, written for health care providers, is available by subscription. (See 'Professional level information' below.)

SYMPTOMS — Most people with pancreatic cancer have abdominal pain and weight loss, with or without jaundice (yellowing of the skin):

●Pain – Pain is a common symptom. It usually develops in the upper abdomen as a dull ache that wraps around to the back. The pain can come and go, and it might get worse after eating.

●Weight loss – Some people lose weight because of a lack of appetite, feeling full after eating only a small amount of food, or diarrhea. The bowel movements might look greasy and float in the toilet bowl because they contain undigested fat.

●Jaundice – Jaundice causes yellow coloring of the skin and whites of the eyes. Bowel movements may not be a normal brown color and instead have a grayish appearance, and the urine may be dark. Jaundice is caused by blockage in the flow of bile through the ducts that come from the liver and gallbladder to the intestine (figure 2), where the bile assists in the digestion of food. The blockage is caused by the cancer.

DIAGNOSIS — If you develop symptoms that raise suspicion for pancreatic cancer, your doctor or nurse will order one or more tests. These might include:

●Blood tests

●Imaging tests – These may include an ultrasound, a computed tomography (CT) scan, or a magnetic resonance imaging study (MRI).

●Endoscopic procedures – Often, endoscopic or interventional procedures of the gastrointestinal tract may be performed including endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP). (See "Patient education: ERCP (endoscopic retrograde cholangiopancreatography) (Beyond the Basics)".)

The imaging and endoscopic tests can show if there is a mass (growth) in the pancreas, if it is involving neighboring structures, or if it has spread to other organs.

●Biopsy – In most cases, your doctor will recommend a biopsy to confirm the diagnosis of cancer. A biopsy involves removing a small piece of tissue from the mass. A clinician examines the tissue under a microscope to see if there are signs of cancer.

To perform the biopsy, a doctor will use a CT scan or ultrasound to pinpoint the location of the mass then insert a needle into the mass and take a sample of tissue. If the mass is located only in the pancreas, a biopsy is usually obtained via endoscopic procedures such as ERCP or EUS.

STAGING — Once pancreatic cancer is diagnosed, the next step is to determine its stage. Staging is a system used to describe the spread of a cancer. A pancreatic cancer's stage is based on the size of the cancer and location of the cancer in the body.

Staging is determined using the following tests:

●Imaging tests – Computed tomography (CT) scan, magnetic resonance imaging (MRI), or other imaging tests to look for spread of cancer outside the pancreas.

●Laparoscopy – Sometimes the staging of a pancreatic cancer is also based on what is found during surgery or a special procedure known as a laparoscopy. This is a type of "minimally invasive surgery." During a laparoscopy, a surgeon inserts a thin tube with a camera into small incisions in the belly to see the organs inside the abdomen. In some centers, a laparoscopy is recommended before an attempt to remove the cancer surgically to get more information on whether it has spread to the liver or other parts of the abdomen.

Pancreatic cancer stages range from stage I, the earliest stage, to stage IV, which means that the cancer has spread to distant organs (such as the lungs or liver). In general, lower stage cancers are more likely to be successfully treated than higher stage cancers. Most clinicians who care for people with pancreatic cancer refer to people as having surgically resectable cancer (stage I and II), locally advanced cancer (stage III), or metastatic cancer (stage IV). (See 'Stage IV (metastatic) pancreatic cancer' below.)

Sometimes you will hear clinicians describe a stage that technically doesn't exist called "borderline resectable." This occurs because some localized cancers can be resected completely, but many cannot. Imaging doesn't always accurately distinguish between the two. In such cases, chemotherapy, with or without radiation therapy, might be used initially to attempt to shrink the tumor and increase the chance that it might become resectable. (See 'Locally advanced pancreatic cancer' below.)

GENETIC TESTING — Anyone with pancreatic cancer should be offered genetic testing, which may affect treatment options (see 'Treatment of pancreatic cancer' below):

●Germline mutations – "Germline" refers to the genes that a person received (inherited) from their parents. The most common form of an inherited predisposition to pancreatic cancer is inheritance of the BRCA genes (also known as the breast cancer genes). Other inherited conditions can also be associated with the development of pancreatic cancer. Referral for genetic counseling is recommended for all patients with pancreatic cancer. (See "Patient education: Genetic testing for hereditary breast, ovarian, prostate, and pancreatic cancer (Beyond the Basics)".)

●Somatic mutations – "Somatic" mutations refer to the genetic changes of the DNA in the tumor as opposed to the DNA in healthy tissue. Identification of genetic changes unique to the tumor may allow options for treatment with specific targeted therapies, including through clinical trials.

●Microsatellite instability – All pancreatic cancers should be tested for something called "microsatellite instability." This involves looking at the tumor for loss of specific proteins involved in repairing tumor cell DNA.

TREATMENT OF PANCREATIC CANCER — Pancreatic cancer can be treated with several approaches, depending upon the stage of the tumor and the person's health. The main treatment options for pancreatic cancer include surgery, chemotherapy, and radiation therapy (RT).

Early stage (surgically resectable) pancreatic cancer — The earliest stage of pancreatic cancers (stages I or II) can often be treated, and even cured, with surgery. However, few people are in the earliest stage when their pancreatic cancer is found. (See 'Surgical approaches' below.)

After surgery, most people often need further treatment, also called "adjuvant therapy." This generally includes chemotherapy and may include radiation therapy. (See 'Adjuvant therapy (treatment after surgery)' below.)

Some people whose tumors could be resected initially may be referred for initial chemotherapy and/or radiation therapy to "downstage" or reduce the tumor and potentially improve outcomes from surgery.

Surgical approaches

Surgery for tumors in the head of the pancreas — The standard operation for tumors in the head of the pancreas (figure 1) is a Whipple procedure. This is also called a "pancreaticoduodenectomy."

In this procedure, the surgeon removes the pancreatic head, the duodenum (the first part of the small intestine), part of the jejunum (the next part of the small intestine), the common bile duct, the gallbladder, and part of the stomach (figure 2). A modification of the Whipple procedure (called a "pylorus-preserving" Whipple procedure) has been developed that preserves the part of the stomach (the pylorus) that is important for stomach emptying.

The Whipple procedure is a complex operation. Better treatment outcomes and less postsurgical complications are more likely in hospitals that perform many Whipple procedures and when the surgeon is experienced with the procedure.

Surgery for tumors in the body or tail of the pancreas — Because tumors in the body or tail of the pancreas do not cause the same symptoms as those in the head of the pancreas, these cancers tend to be discovered at a later stage when they are more advanced.

If the tumor can be removed with surgery, a laparoscopy is usually done first to make sure the cancer has not spread. If surgery is an option, part of the pancreas is removed, usually along with the spleen.

Adjuvant therapy (treatment after surgery) — Adjuvant (additional) therapy refers to chemotherapy, radiation, or a combination of both. Adjuvant therapy is recommended for people who are at high risk of having cancer reappear (termed a "recurrence" or "relapse") after a tumor has been removed surgically.

Even if the tumor has been completely removed, tiny cancer cells may remain in the body and grow, causing relapse after surgery. Adjuvant therapy can increase cure rates and prolong survival by eliminating the tiny cancer cells before they have a chance to grow.

In people with completely resected pancreatic cancer, there are two ways to give adjuvant therapy after surgery:

●Give chemotherapy alone.

●Give a combination of chemotherapy and radiation therapy (this strategy is called "chemoradiation").

In the United States, after successful surgical removal of a pancreatic cancer, chemotherapy alone is generally given. However, some people at high risk of local recurrence (ie, tumor coming back around the site of surgery) will also receive chemoradiation.

Locally advanced pancreatic cancer — In locally advanced pancreatic cancer, the cancer has extended into areas around the pancreas that make it difficult or impossible to remove it completely using surgery alone but has not yet spread to distant locations. Using imaging studies and standard guidelines, some of these cases may be classified as "borderline" resectable, while others are locally advanced and not resectable. (See 'Staging' above.)

Chemotherapy — The best treatment for locally advanced pancreatic cancer is to start with systemic therapy (specifically, chemotherapy). The purpose of the chemotherapy is to cause the tumor to shrink enough to allow for surgery. Often, a person will receive radiation therapy after chemotherapy and prior to an attempt at surgical removal.

The choice of regimen is based on several factors, including how healthy a person is before starting therapy, and involves discussion with the treating clinician. Two common regimens used to treat pancreatic cancer include:

●FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin)

●Gemcitabine plus nab-paclitaxel

Radiation therapy — Radiation therapy may be included in the treatment of locally advanced pancreatic cancer. Radiation therapy is delivered while the person lies on a table underneath or in front of the machine. The treatment takes only a few seconds, similar to having an x-ray.

The choice of radiation therapy delivery depends on tumor anatomy (ie, size, shape, contact with important internal structures) and the experience of the radiation oncologist. The radiation therapy schedule depends on whether the goal is to shrink the tumor and increase the chances of surgical removal, or to treat the tumor completely without surgery.

Radiation therapy can be delivered in several different ways.

●Chemoradiation – Chemoradiation combines radiation therapy with chemotherapy. Most people receive radiation therapy five days per week typically for five to six weeks, although the treatment duration could be as short as two to three weeks. Chemotherapy (administered either oral or intravenously) is also administered at the same time with radiation therapy to make it more effective.

●Stereotactic body radiotherapy – Stereotactic body radiation therapy (SBRT) is an alternative option for radiation therapy delivery. SBRT involves a shorter treatment course of five days and is given without chemotherapy.

Surgery — Increasingly, surgeons are attempting to remove locally advanced pancreatic cancer after several months of systemic therapy (and possibly radiation therapy). (See 'Surgical approaches' above.)

People who are unable to undergo surgery may continue systemic therapy, similar to those with stage IV (metastatic) disease. (See 'Stage IV (metastatic) pancreatic cancer' below.)

Stage IV (metastatic) pancreatic cancer — People who are diagnosed with stage IV (or metastatic) pancreatic cancer have disease that has spread to distant locations outside of the pancreas.

Systemic therapy — Systemic therapies (ie, drugs that are administered intravenously or orally) are typically used to treat these tumors.

●Chemotherapy – Chemotherapy is the most common form of systemic therapy used to treat pancreatic cancer. Many of the chemotherapy regimens used in pancreatic cancer are similar across different disease stages.

Depending on the specific kind of cancer and its genetic makeup (see 'Genetic testing' above), some people may be candidates for other types of treatment, such as:

●Immunotherapy – Immunotherapy refers to drugs that stimulate or unleash your immune system to attack and kill the cancer cells. "Immune checkpoint inhibitor" drugs, though not broadly effective in pancreatic cancer, can be used to treat certain rare subtypes of pancreatic cancer that show mismatch repair deficiency (also known as microsatellite instability).

●Poly adenosine diphosphate-ribose polymerase (PARP) inhibitors – For people with a mutation in the BRCA1, BRCA2, or PALB2 genes (which are associated with an increased risk of certain types of cancer, including pancreatic cancer), a PARP inhibitor drug such as olaparib may be recommended if the cancer did not progress after a period of chemotherapy.

These therapies do not cure metastatic pancreatic cancer, but they can relieve symptoms, slow the spread of the cancer, and prolong life. Talk to your doctor about the benefits and risks of chemotherapy. Your doctor might suggest participating in a clinical trial that compares new chemotherapy medicines or new combinations of treatment. (See 'Clinical trials' below.)

TREATMENT OF CANCER-RELATED SYMPTOMS — Pancreatic cancer often causes bothersome symptoms like jaundice, intestinal blockage, pain, and weight loss. Treatments are available to relieve these symptoms.

Jaundice — Jaundice is caused by a blockage of the flow of bile from the liver into the intestine (figure 2). The most common treatment is a stent, which is a small tube that is inserted into the bile duct to keep it open. The stent is usually placed in a procedure called endoscopic retrograde cholangiopancreatography (ERCP). More information on this procedure is available separately. (See "Patient education: ERCP (endoscopic retrograde cholangiopancreatography) (Beyond the Basics)".)

Intestinal blockage — Some people with pancreatic cancer will develop a blockage in the upper intestine (duodenum) caused by the tumor (figure 1). Surgery can be done to create a detour between the stomach and a lower part of the intestine. An alternative to bypass surgery is placement of a stent (tube) in the duodenum. The stent helps to hold open the blocked area.

Pain — Pain is a common problem with pancreatic cancer. In some cases, prescription pain medicine alone is all that is needed. Radiation therapy can also help relieve pain by shrinking the tumor.

A procedure called a "celiac plexus block" might also be a good option to control pain. This procedure uses injections of alcohol into nerves that transmit pain signals. The alcohol kills the nerves, preventing them from telling the brain to feel pain.

Weight loss — Weight loss is common with pancreatic cancer. Taking a pancreatic enzyme replacement can help your body to digest and absorb fat and protein. Enzyme replacements are usually taken in the form of capsules during meals. A nutrition consultation may be appropriate.

If nausea and vomiting are a problem, there are several medicines that can reduce these symptoms and improve the appetite.

ADVANCED CANCER AND END OF LIFE CARE — In many people with pancreatic cancer, the disease cannot be cured. Deciding when to stop treating the cancer can be difficult, and the decision should involve the individual, their loved ones, and the health care team.

Ending cancer treatment does not mean ending care for the person. Hospice care is frequently recommended when a person is unlikely to live longer than six months. Hospice care involves treatment of all aspects of a patient and family's needs, including the physical (eg, pain relief), psychological, social, and spiritual aspects of suffering. This care may be given at home or in a nursing home or hospice facility, and it usually involves multiple care providers, including a clinician, registered nurse, nursing aide, chaplain or religious leader, social worker, and volunteers.

These providers work together to meet the patient and family's needs and significantly reduce their suffering. For more information about hospice, see www.nhpco.org/hospice-care-overview.

CLINICAL TRIALS — Progress in treating cancer requires that better treatments be identified through clinical trials, which are conducted all over the world. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask for more information about clinical trials, or read about clinical trials at:

●www.cancer.gov/clinicaltrials/

●http://clinicaltrials.gov/

Videos addressing common questions about clinical trials are available from the American Society of Clinical Oncology (https://www.cancer.net/research-and-advocacy/clinical-trials/welcome-pre-act).

WHERE TO GET MORE INFORMATION — Your health care provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Pancreatic cancer (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient education: ERCP (endoscopic retrograde cholangiopancreatography) (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Treatment for potentially resectable exocrine pancreatic cancer
Initial systemic chemotherapy for metastatic exocrine pancreatic cancer
Clinical manifestations, diagnosis, and staging of exocrine pancreatic cancer
Endoscopic ultrasound in the staging of exocrine pancreatic cancer
Supportive care for locally advanced or metastatic exocrine pancreatic cancer
Initial chemotherapy and radiation for nonmetastatic, locally advanced, unresectable and borderline resectable, exocrine pancreatic cancer
Overview of surgery in the treatment of exocrine pancreatic cancer and prognosis
Hospice: Philosophy of care and appropriate utilization in the United States

The following organizations also provide reliable health information.

●National Cancer Institute

1-800-4-CANCER

(www.cancer.gov)

●American Society of Clinical Oncology

(www.cancer.net/pancreatic)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges David P Ryan, MD, who contributed to earlier versions of this topic review.