Pancreatic cancer

What is pancreatic cancer?^{1 2}

Pancreatic cancer is a much feared disease due to its notoriously late presentation, early metastases and poor survival rates. Only 26% present at stage 1 or 2 and the overall five-year survival rate is 7.8%. Pancreatic cancer survival has not shown much improvement in the last 50 years in the UK.

In the UK, pancreatic cancer is the 5th most common cause of cancer death, despite being the 10th most common cancer overall. 95% of pancreatic cancers are adenocarcinomas.

The pancreas has dual exocrine and endocrine function. Most pancreatic malignancies are exocrine tumours. There is a separate Pancreatic endocrine tumours article.

Infiltrating ductal adenocarcinomas account for around 80% of pancreatic cancers. The majority arise in the head, neck, or uncinate process. Pancreatic cancers arising from the distal common bile duct, the ampulla of Vater, and the duodenum carry a better prognosis as they present with obstructive jaundice at an earlier stage.

Pancreatic cancer epidemiology

Pancreatic cancer incidence¹

• Incidence rates for pancreatic cancer in the UK are highest in people aged 90 or older, who account for 6% of all new diagnoses. 47% of all new pancreatic cancer cases in the UK are diagnosed in people aged 75 and over.

• There is no significant difference in incidence between males and females - pancreatic cancer accounts for 3% of all new cancer cases in both males and females.

• Since the early 1990s, incidence rates have increased by 21% in the UK. Rates in females have increased by 24%, and rates in males have increased by 16%.

• Pancreatic cancer incidence rates in England are higher in deprived areas.

• Pancreatic cancer incidence occurs more commonly in Black ethnic groups than White ethnic groups, and less commonly than both of these in Asian ethnic groups.

Pancreatic cancer risk factors³²

• The main risk factors are smoking, diet (high BMI, red meat intake, low fruit and vegetables intake), diabetes and alcohol intake.

• Chronic and hereditary pancreatitis: chronic pancreatitis is associated with a 3-fold increase in risk and hereditary pancreatitis with a >50-fold increase.

• Family history of pancreatic cancer

• Familial cancer syndromes: BRCA1, BRCA2, familial adenomatous polyposis, Peutz-Jeghers syndrome, familial melanoma syndromes, Lynch syndrome, von Hippel-Lindau syndrome, multiple endocrine neoplasia type 1, Gardner's syndrome.

• Other medical conditions: inflammatory bowel disease,⁴ periodontal disease,⁵ and gastric (but not duodenal) ulcer disease.⁶

Pancreatic cancer symptoms⁷

Early pancreatic cancer symptoms are often vague and nonspecific (frequently epigastric discomfort or dull backache) and their significance is frequently overlooked. More than two thirds occur in the head of the pancreas and classically present with painless, progressive, obstructive jaundice.

Tumours in the body and tail of the pancreas generally occur in patients presenting with fatigue, nonspecific pain and weight loss and are much less likely to cause obstructive signs and symptoms.

Presentation may be due to paraneoplastic processes - eg, thromboembolic disease.

• Abdominal pain: typically located in the epigastric region, radiating through to the back. Can present as simple back pain. Back pain is typically dull and worse when supine and eased by sitting forward.

• Jaundice: obstructive jaundice causes dark urine, pale stools and pruritus.

• Acute pancreatitis: pancreatic cancer should be considered in the differential diagnosis of any elderly patient presenting for the first time with acute pancreatitis, particularly in the absence of known precipitating factors such as gallstones or alcohol abuse.⁸

• Unexplained weight loss, anorexia.

• Steatorrhoea due to malabsorption.

• Epigastric mass (late).

• Palpable gallbladder: Courvoisier's sign (a palpable gallbladder in the presence of painless jaundice) occurs in fewer than 25% of patients.

• Compression of the duodenum or the stomach may cause gastric outlet obstruction or delayed gastric emptying, leading to nausea and vomiting.

• Haematemesis, melaena or iron-deficiency anaemia.

Patients presenting with rapid weight loss, persistent back pain, ascites, an epigastric mass or enlarged supraclavicular node (Virchow's node) are likely to have advanced pancreatic cancer.

Pancreatic cancer differential diagnosis

The differential diagnosis of upper right-sided or epigastric abdominal pain is wide and can include:

• Gallstone disease.

• Peptic ulceration.

• Gastric cancer or colorectal cancer.

• Oesophagitis.

• Hepatitis.

• Liver abscess.

• Primary or secondary liver tumours.

• Right-sided heart failure.

• Pneumonia.

• Pulmonary embolism.

• Aortic aneurysm.

• Pancreatitis.

Differential diagnosis of obstructive jaundice or extrahepatic cholestasis includes:

• Bile duct strictures (benign or malignant).

• Common duct stone.

• Pancreatitis.

• Cholangiocarcinoma.

Investigations

Initial blood tests

The following tests may be appropriate, but referral on a suspected cancer pathway should not be delayed to wait for the results.

• FBC - normochromic anaemia, thrombocytosis or both.

• LFTs - to confirm jaundice (raised bilirubin, usually with predominantly raised alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) or hepatocellular involvement.

• Tumour markers are not appropriate for use in primary care.

Referral⁹

The National Institute for Health and Care Excellence (NICE) recommends that those aged 40 or over with jaundice are referred on a suspected cancer pathway referral for pancreatic cancer. Those on this pathway should have a cancer diagnosed or excluded within 28 days.

It also suggests that an urgent direct access CT scan (or ultrasound if CT is not available) be requested in those aged 60 or over with weight loss and any of the following:

• Diarrhoea.

• Back pain.

• Abdominal pain.

• Nausea or vomiting.

• Constipation.

• New-onset diabetes.

CT scan is more sensitive than ultrasound for the diagnosis of pancreatic cancer.

Pancreatic cancer staging

Staging is based on the TNM system

• TIS = in situ carcinoma; T1 = tumour limited to pancreas but <2 cm; T2 = tumour limited to pancreas but larger than 2 cm; T3 = tumour extends beyond the pancreas but not into the coeliac axis or superior mesenteric artery; T4 = tumour involves coeliac axis or superior mesenteric artery.

• N0 = no regional lymph node metastasis; N1 = regional lymph node metastasis.

• M0 = no distant metastasis; M1 = distant metastasis.

Pancreatic cancer histology

Primary solid non-endocrine epithelial tumours

• Ductal adenocarcinoma (75-90%).

• Adenosquamous carcinoma.

• Acinar cell carcinoma.

• Giant cell carcinoma.

• Pancreatoblastoma.

Primary cystic non-endocrine epithelial tumours

• Serous cystic neoplasms.

• Mucinous cystic neoplasms.

• Intraductal papillary-mucinous neoplasms.

• Solid and cystic papillary neoplasms.

• Acinar cell cystadenocarcinoma.

Most non-inflammatory pancreatic cysts are malignant or pre-malignant - the main differential diagnosis is a pancreatic pseudocyst. Patients with pancreatic cysts are at an increased risk of developing other cancers of the pancreas but also extrapancreatic cancer. Serous cystadenomas are nearly always benign and are usually managed conservatively under radiological surveillance.

Pancreatic cancer treatment and management¹⁰

When pancreatic cancer is suspected on the basis of clinical and radiological findings, patients should be referred to designated pancreatic cancer centres for further assessment and treatment. Management will include not only treating the tumour but also psychological support, pain management and relief of biliary obstruction as required.

Specifics of management will depend on the stage at diagnosis and the patient's fitness for surgery. It may include surgery, chemotherapy or chemoradiotherapy. For some patients who present with advanced disease, management will be palliative from the start.

Palliative care

See also the separate Palliative care article.

Pain control

• Pain occurs in over 50% and may be severe and difficult to manage.

• Where opiates fail to control pain or are contra-indicated/poorly tolerated, early referral to a specialist palliative team is important - alternative analgesia, ablation of the coeliac ganglia, or external beam radiotherapy may provide significant improvement.

• Coeliac plexus block (an injection of local anaesthetic into or around the coeliac plexus of nerves) is effective for the treatment of severe upper abdominal pain associated with pancreatic cancer.¹¹

Malabsorption and weight loss

Quality of life and steatorrhoea can be improved by the use of pancreatin supplements, titrated to prevent diarrhoea. See also the separate Nutritional support in primary care article.

Nausea and vomiting

Nausea and vomiting often occur. They are often due to slowed gastric emptying and are improved by prokinetic agents such as metoclopramide or domperidone. If due to duodenal obstruction, duodenal stenting or bypass may be required.

Depression

There is a stronger association with pancreatic cancer compared with other malignancies so a low threshold for intervention and treatment may be appropriate.

Complications

• Obstructive jaundice.

• Duodenal obstruction.

• Deep vein thrombosis, pulmonary embolus.

• Intractable pain (due to parenchymal pressure secondary to ductal obstruction, neural infiltration, pancreatic inflammation and associated biliary stenosis).

Prognosis¹

• Average survival is as follows:

  • Ten years - 4.3% (UK).

  • Five years - 7.8% (England).

  • One year - 24.8% (UK).

• Survival is strongly related to age - for example 17.6% of men diagnosed at 44 or younger survive for ten years, compared to only 1.7% of men diagnosed at 75 or older.

Prevention

• Reducing tobacco and alcohol consumption is likely to reduce cases of pancreatic cancer.

• Physical activity, high fruit and vegetable intake, and avoiding central obesity may have a protective effect.

Pancreatic cancer surveillance¹⁰

Secondary screening has been recommended for high-risk patients (chronic pancreatitis, hereditary pancreatitis, familial pancreatic cancer, ovarian and breast cancer familial syndrome and familial multiple mole melanoma syndrome).

NICE recommends surveillance for pancreatic cancer to people with:

• Hereditary pancreatitis and a PRSS1 mutation.

• BRCA1, BRCA2, PALB2 or CDKN2A (p16) mutations, and one or more first-degree relatives with pancreatic cancer.

• Peutz-Jeghers syndrome.

Consider surveillance for pancreatic cancer for people with:

• Two or more first-degree relatives with pancreatic cancer, across two or more generations.

• Lynch syndrome (mismatch repair gene [MLH1, MSH2, MSH6 or PMS2] mutations) and any first-degree relatives with pancreatic cancer.

The EUROPAC trial¹² is investigating inherited pancreatic cancer - it closed to new registrations in January 2026.