Cancer of the pancreas is one of the deadliest cancer types. Most pancreatic cancer patients will die within the first year of diagnosis, and just 6% will survive five years.
Over the past decade, pancreatic cancer death rates have been slowly increasing among US men and women, in contrast to the downward trend in rates for most other major cancer sites, such as lung, colorectum, female breast, and prostate. The lack of progress in primary prevention, early diagnosis, and treatment underscores the need for additional efforts in pancreatic cancer research and has motivated us to address this disease in the current edition of Cancer Facts & Figures. Specifically, this section provides updated information on occurrence, prevention, early detection, diagnosis, and treatment of pancreatic cancer.
The pancreas contains two types of glands that each perform very different functions. The exocrine glands produce enzymes that help digest food; the endocrine glands produce important hormones such as insulin, which regulates blood sugar levels. Exocrine and endocrine cells form completely different types of tumors with distinct risk factors, symptoms, diagnostic tests, treatment, and survival rates. Exocrine tumors are the focus of this special section because they are by far the most common type of pancreatic cancer, representing about 95% of cases.
The causes of pancreatic cancer are not well understood, though there are several factors known to increase risk. Known modifiable risk factors include obesity, cigarette smoking, and other forms of tobacco use. Risk factors that are not modifiable include a family history of pancreatic cancer and certain inherited syndromes. Strategies for preventing pancreatic cancer include not smoking and maintaining normal body weight. Consuming adequate quantities of fruits and vegetables may also have a preventive effect, although strong evidence for this association is lacking.
Tobacco use is the most important known risk factor for pancreatic cancer; approximately 20% of pancreatic cancers are attributable to cigarette smoking. The risk of developing pancreatic cancer is about twice as high among smokers as among never smokers; risk increases with greater tobacco use and longer duration of smoking. Cigar and pipe smoking also increase risk. Quitting smoking rapidly reduces the risk of pancreatic cancer; after 5-10 years of cessation, the risk among former smokers returns to that of never smokers. Use of smokeless tobacco products also increases the risk of pancreatic cancer. Evidence on secondhand smoke exposure and pancreatic cancer is inconsistent.
Obesity has also been fairly consistently linked to increased risk of pancreatic cancer. Obese individuals have a 20% higher risk of developing pancreatic cancer than those who are normal weight. Being obese during early adulthood may be associated with an even greater risk of pancreatic cancer and a younger age of disease onset. Abdominal obesity may increase risk independent of general obesity, especially in women.
Results regarding the association between physical activity and pancreatic cancer risk are mixed. A slightly decreased risk of pancreatic cancer was linked to total and occupational physical activity in a recent literature review but not in a previous one. There is currently limited evidence to support a protective effect of recreational physical activity on risk of pancreatic cancer.
Whether alcohol use causes pancreatic cancer remains to be determined. A positive association between alcohol use and pancreatic cancer was found in several but not all studies. Accumulating evidence suggests that a moderate increased risk is limited to heavy alcohol users. A recent meta-analysis showed that consumption of three or more drinks of alcohol per day is associated with a 20% to 30% increased risk of pancreatic cancer. However, due to the strong relationship between alcohol consumption and tobacco use, it is difficult to eliminate the effect of smoking when studying the association between alcohol drinking and pancreatic cancer risk.
A number of dietary factors have been assessed regarding their association with pancreatic cancer risk. There is some evidence that the consumption of red and processed meat may slightly increase risk. Investigators have also found some evidence for increased risk among those who consume meat that has been cooked at very high temperatures. A protective effect of folate intake on pancreatic cancer risk has been reported in several studies; however, a recent large analysis found no association. At present, there is limited evidence supporting a protective effect of fruit and vegetable consumption on the risk of pancreatic cancer. No association between coffee consumption and pancreatic cancer was found in a recent analysis that combined many studies.
A number of studies have linked family history to an increased risk of pancreatic cancer. Generally, individuals with a family history of pancreatic cancer have a nearly 2-fold increased risk for developing pancreatic cancer, compared to those without such a history. The risk increases to 7- to 9-fold for individuals with at least 1 first-degree relative (a parent or sibling) with pancreatic cancer and 17- to 32-fold for individuals with 3 or more firstdegree relatives with pancreatic cancer. Risk is also increased if a first-degree relative was diagnosed with pancreatic cancer before age.
Accumulating evidence suggests that long-standing chronic pancreatitis is a strong risk factor for pancreatic cancer, though pancreatitis may also be an early indicator of pancreatic cancer. After excluding the pancreatic cancer cases diagnosed within 2 years from chronic pancreatitis diagnosis, a review study reported a 6-fold increased risk of pancreatic cancer among patients with chronic pancreatitis. The risk is especially strong in patients with rare types of pancreatitis, such as hereditary pancreatitis and tropical pancreatitis. The lag period between pancreatitis diagnosis and pancreatic cancer onset is usually about 10 to 20 years. Despite the strong association between chronic pancreatitis and pancreatic cancer, chronic pancreatitis is uncommon; moreover, only about 4% of these patients will develop pancreatic cancer within 20 years of diagnosis.
About 25% of patients with pancreatic cancer have diabetes mellitus at diagnosis, and roughly another 40% have pre-diabetes (higher than normal blood glucose levels). Compared with non-diabetic individuals, patients with long-term (≥ 5 years) type-II diabetes have a 50% increased risk of pancreatic cancer. Pancreatic cancer can cause diabetes, and sometimes diabetes is an early sign of the tumor. Elevated pancreatic cancer risk has also been reported among individuals with type-I diabetes. Recent reports also suggest that hyperglycemia (high blood glucose), abnormal glucose metabolism, and insulin resistance are associated with increased risk of pancreatic cancer.
Several studies have detected an increased risk of pancreatic cancer among people with chronic infections with hepatitis B virus, hepatitis C virus and Helicobacter pylori. Individuals with a history of cholecystectomy (surgical removal of the gallbladder) or partial gastrectomy (partial surgical removal of the stomach) have also been found to be at increased risk of developing pancreatic cancer. Other medical conditions that may increase risk include cystic fibrosis75 and periodontal disease.
Early stage pancreatic cancer usually has no symptoms. When symptoms do occur, the tumor has usually spread to surrounding tissues or distant organs. Common symptoms of pancreatic cancer include mild abdominal discomfort, mid-back pain, jaundice (yellowing of the skin or whites of the eyes), and weight loss. Nausea and vomiting may occur among patients with more advanced disease. In the US, only about 15% to 20% of pancreatic cancer cases are diagnosed early enough to be eligible for surgery.
To date, there is no single, reliable test for the early detection of pancreatic cancer; therefore, screening the general population is not recommended by any health agency. Existing screening programs have been limited to research settings with a focus on detecting precancerous lesions among high-risk individuals.
The most frequently tested techniques for pancreatic cancer screening include endoscopic ultrasound (EUS), helical computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic retrograde cholangiopancreatography (ERCP). Single use of EUS or various combinations of these imaging techniques are capable of detecting early pancreatic cancer or precancer in high-risk patients, such as those with chronic, hereditary, or tropical pancreatitis; Peutz-Jeghers syndrome; cystic fibrosis; or familial atypical multiple mole-melanoma. However, it remains unclear whether screening high-risk populations is effective in reducing pancreatic cancer mortality. Therefore, pancreatic cancer screening should currently be limited to high-risk populations within a research setting. Recent advances in understanding the molecular basis of cancer offer promise for the discovery of new methods for detecting pancreatic cancer early.
When pancreatic cancer is suspected, patients will be asked to provide a full medical history and be given a physical exam mainly focused on the abdomen, but also of the skin and eyes for indications of jaundice (yellow coloring). Pancreatic cancer is typically diagnosed with the use of an imaging test, usually a CT scan, often with a contrast dye, given by mouth or through injection, to better outline abnormal areas. This procedure is also often used to stage the tumor, with 70% to 85% accuracy for predicting whether or not the tumor can be surgically removed. If pancreatic cancer is highly suspected but a CT scan appears normal, additional diagnostic tests, such as endoscopic ultrasound or ERCP, may be performed. The ERCP technique is especially useful in patients with bile duct tumors and endoscopic ultrasound can often detect small tumors missed by CT scan. A cancer diagnosis is typically confirmed with a biopsy – a procedure in which a small sample of the tumor is removed and viewed under a microscope. The most common type of biopsy to confirm pancreatic cancer is called a fine needle aspiration biopsy. The needle is inserted into the pancreas guided by an endoscopic ultrasound or CT scan images to obtain tissues for evaluation. However, a tissue diagnosis is not needed for patients who are scheduled for surgery. Due to the deep location of the pancreas and the medical complications of biopsy, pancreatic cancer is the least likely of all major cancers to be microscopically confirmed.
Patients with pancreatic cancer are best managed by a multidisciplinary team, including surgeons, medical and radiation oncologists, radiologists, gastroenterologists, pain management experts, nutritionists, social workers, and others. The treatment choice is largely determined by whether the tumor can be surgically removed. Surgery remains the only treatment that offers a chance of cure for pancreatic cancer patients.
For those patients who are candidates for surgery (approximately 20% of all pancreatic cancer patients), the operative approaches include cephalic pancreatoduodenectomy (the Whipple procedure), distal pancreatectomy, or total pancreatectomy, depending on the location of the tumor. Postoperative (adjuvant) chemotherapy either alone or in combination with radiation has been proven to improve progression-free and overall survival in both randomized controlled trials and observational studies. The role of radiation therapy by itself in the adjuvant setting remains unclear. Treatment with chemotherapy or chemoradiotherapy prior to surgery (neoadjuvant) is an emerging strategy. The goal of neoadjuvant treatment is to increase the ability to successfully remove all of the tumor. However, there is no evidence that neoadjuvant therapy is superior to adjuvant therapy, especially among those patients who clearly have resectable disease. For this reason, neoadjuvant treatment is considered more relevant for patients with locally advanced or borderline resectable disease.
The treatment for patients with advanced disease focuses on managing symptoms and relieving pain and suffering (palliative care). Treatment options include chemotherapy alone or in combination with radiation. The combination of 5-FU, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) can help prolong life in patients with advanced disease, though many patients are too ill to tolerate this regimen. Other treatment options include gemcitabine alone or in combination with a platinum agent, erlotinib (Tarceva), or fluoropyrimidine.
Given the poor survival and persistent symptoms experienced by many pancreatic cancer patients who do not respond to treatment, care focusing on relieving and preventing suffering represents an important aspect of managing this disease. Palliative care should be offered at the initiation of any treatment regimen in order to relieve symptoms and side effects, which include pain, bile duct or gastric outlet obstruction, and loss of appetite. Palliative efforts may also include psychological support to relieve patients’ stresses associated with pancreatic cancer diagnosis and treatment.
Opioid analgesics (morphine and similar drugs) are often needed to help reduce pain. Radiation may be given to help relieve pain from locally advanced disease. Another pain management approach is nerve block, whereby a pain specialist injects either an anesthetic or a medication to block or destroy the nerves. For example, abdominal pain can sometimes be treated effectively by endoscopic ultrasound or CT guided celiac plexus block.
If the tumor is blocking the bile duct, a stent (a thin tube) can be placed to relieve the blockage using nonsurgical approaches, such as ERCP and percutaneous transhepatic cholangiogram (PTC). If a patient develops gastric-outlet obstruction, treatment may include duodenal wall stents or PEG (percutaneous endoscopic gastrostomy) placement for decompression. Sometimes, a patient may need surgery to create a bypass (biliary bypass or gastric bypass) to manage obstructive jaundice and gastric outlet obstruction.
If the pancreas is not working well or has been partially or entirely removed, a special diet and specially prescribed enzymes may help the patient’s digestion. Meeting with a nutritionist is also often very helpful for patients who are losing weight and have a poor appetite because of their disease.