Pancreatic cancer is the fourth leading cause of cancer deaths in the US and typically affects older individuals in the sixth to eighth decades of life. Underlying risk factors include smoking, obesity, heavy alcohol consumption, and chronic pancreatitis. Pancreatic carcinomas are mostly ductal adenocarcinomas and frequently located in the pancreatic head. The disease is commonly diagnosed at an advanced stage because of the late onset of clinical features (e.g., epigastric pain, painless jaundice, and weight loss). In many cases, the tumor has already spread to other organs (mainly the liver) when it is diagnosed. Treatment is often palliative as surgical resection is only possible in approx. 20% of cases. The most commonly used surgical technique is the pancreaticoduodenectomy (Whipple procedure). Five-year survival rates range from 3–40% depending on the extent, spread, and resectability of the tumor. Occasionally, small, potentially resectable pancreatic lesions can be discovered on imaging. These can represent benign, precancerous, or malignant lesions. Management varies by lesion type, e.g., pancreatic cystic lesions, pancreatic neuroendocrine tumors. Screening is not routinely performed but is recommended for select high-risk individuals.
- Age of onset: : 60–80 years 
- ∼ 3% of all new cancers in the US
- In 2020, 57,600 individuals in the US will be newly diagnosed with pancreatic cancer (♂ > ♀)
- Mortality: accounts for ∼ 8% of all cancer deaths in the US
High-risk groups 
- African Americans
- Individuals of Jewish ancestry
Epidemiological data refers to the US, unless otherwise specified.
Exogenous risk factors 
- Smoking (strongest risk factor)
- Chronic pancreatitis (especially when present for more than 20 years)
- High alcohol consumption
- Type 2 diabetes mellitus
- Occupational exposure to chemicals used in the dry cleaning and metalworking industries
- Possibly infections with:
- H. pylori (and excess stomach acid)
- Hepatitis B
Endogenous risk factors 
- Age > 50 years
Inherited genetic syndromes (10% of pancreatic cancers)
- Familial atypical multiple mole melanoma (FAMMM) syndrome
- Hereditary breast and ovarian cancer syndrome (BRCA1 and BRCA2 mutations)
- Von-Hippel-Lindau syndrome
- Neurofibromatosis type 1
- Multiple endocrine neoplasia type 1
- Familial pancreatic carcinoma
- Hereditary pancreatitis (mutations in the PRSS1 gene)
- Peutz-Jeghers syndrome
In most cases, there are no early symptoms suggestive of pancreatic cancer. 
- Poor appetite
- Weight loss
- Belt-shaped epigastric pain which may radiate to the back
- Malabsorption, diarrhea (possibly steatorrhea secondary to exocrine pancreatic insufficiency)
Jaundice caused by obstruction of extrahepatic bile ducts (especially in tumors of the pancreatic head)
- Courvoisier sign: enlarged, nontender gallbladder and painless jaundice
- Pale stools, dark urine, and pruritus
- Impaired glucose tolerance (rarely)
Trousseau syndrome: superficial thrombophlebitis (in 10% of cases)
- Recurring thrombophlebitis in changing locations (migratory)
- Red, tender extremities
- Classically associated with pancreatic cancer
- Thrombosis (e.g., phlebothrombosis, splenic vein thrombosis)
A thrombosis of unknown origin may be caused by an undiagnosed malignancy (especially pancreatic cancer, but also pulmonary, and prostatic carcinoma, the "3P's").
The symptoms of pancreatic cancer may be similar to those of chronic pancreatitis. Differential diagnosis is difficult since carcinoma may be accompanied by pancreatitis.
In the majority of instances, pancreatic cancer is diagnosed in symptomatic patients once it has already spread regionally or distally and is no longer resectable. If identified at an early stage (e.g., as an incidentaloma), lesions may be resectable. Initial testing is guided by clinical presentation. Consider screening for high-risk asymptomatic individuals (see “Prevention”). 
Unexplained epigastric pain, RUQ pain, and/or jaundice
- Obtain abdomen ultrasound as initial imaging.
- Include liver chemistries, lipase, and amylase in laboratory studies.
- See also “Abdominal pain” and “Jaundice and cholestasis”
- High clinical suspicion for abdominal malignancy : Consider CT abdomen and pelvis with IV contrast as initial imaging.
Indeterminate pancreatic lesions on imaging (e.g., found during workup or screening, including incidentalomas) 
- Obtain pancreas protocol imaging (CT or MRI).
- Consider advanced testing (e.g., EUS, MRCP) based on findings or if the diagnosis remains uncertain.
- Arrange tissue sampling for histopathology in most patients.
- See also “Pancreatic cystic lesions” and “Pancreatic neuroendocrine tumors.”
Confirmed pancreatic malignancy
- Obtain imaging for preoperative staging to assess local and distant spread and determine resectability.
- Measure baseline tumor markers.
- Perform genetic testing for individuals with a positive family history or suspected genetic syndrome (see “Endogenous risk factors”).
Pancreatic incidentalomas should be investigated early and evaluated for curative resection.
Initial diagnostic imaging 
Used to identify potentially malignant lesions and evaluate for resectability
- Ultrasound abdomen: often the initial recommended test, especially if the patient presents with jaundice
CT abdomen (with PO water and IV contrast; pancreas-specific triphasic protocol)
- To confirm ultrasound findings if a pancreatic mass is detected
- To evaluate spread to adjacent structures and determine resectability
- If clinical suspicion remains high despite a negative ultrasound
- Performed as initial imaging if abdominal pain and weight loss are the initial presenting symptoms
- MRI abdomen: alternative if CT is contraindicated 
Findings of pancreatic adenocarcinoma (See “Pancreatic cystic lesions” for other findings.)
- Poorly defined, hypodense/hypoechoic and hypovascular mass
- Double-duct sign: dilation of the common bile duct and pancreatic duct due to tumors of the pancreatic head blocking bile drainage.
Routine laboratory studies 
Findings are variable and nonspecific but may show abnormalities caused by pancreatic cancer or related complications.
- Obtain CBC, BMP, pancreatic enzymes, liver chemistries, and liver function parameters.
- Increased lipase and/or cholestatic enzymes can occur due to the presence of obstructive tumors (typically of the pancreatic head).
- Other abnormalities may occur due to:
- Chronic illnesses such as anemia and malnutrition (abnormalities include coagulopathy and hypoalbuminemia)
- Pancreatic endocrine dysfunction (e.g., hyperglycemia can occur due to secondary diabetes mellitus)
- Liver or kidney dysfunction
Diagnostic confirmation 
Endoscopic ultrasound (EUS)
- Used to confirm the diagnosis and determine resectability when other studies are inconclusive
- Can be combined with FNA for tissue sampling
Tissue sampling: required for most patients with pancreatic masses or suspicious pancreatic cysts on imaging ; 
- Typically obtained EUS-guided
- Alternatives: percutaneous ultrasound- or CT-guided biopsy
- Can help differentiate pancreatic cancer from pancreatitis and other malignant and nonmalignant lesions (e.g., metastases, benign neoplasms)
A negative biopsy does not rule out pancreatic cancer in patients with highly concerning imaging findings; consider repeat preoperative or intraoperative sampling in such cases.
- Typically used to rule out choledocholithiasis and assess if biliary decompression is indicated
- Can be used adjunctively to evaluate local tumor extension 
- ERCP: usually used when biliary decompression is indicated
- Tumor markers: not recommended for diagnosis or screening ; 
Imaging for preoperative staging 
Required to assess the extent of the tumor, the involvement of local key vascular structures, and to identify metastatic disease
Once the diagnosis is confirmed, pancreatic cancer should be staged to determine management. The American Joint Committee for Cancer (AJCC) TNM classification is currently the standard staging system used in clinical practice.
|Pancreatic cancer staging system |
|T1||Maximum tumor diameter ≤ 2 cm|
|T2||Maximum tumor diameter > 2 cm and ≤ 4 cm|
|T3||Maximum tumor diameter > 4 cm|
|T4||Tumor involves the celiac axis, common hepatic artery, and/or superior mesenteric artery|
|N0||No regional lymph node involvement|
|N1||Involvement of 1–3 regional lymph nodes|
|N2||Involvement of ≥ 4 regional lymph nodes|
|M0||No distant metastases|
|Stage IA||T1, N0, M0|
|Stage IB||T2, N0, M0|
|Stage IIA||T3, N0, M0|
|Stage IIB||Up to T3, N1, M0|
|Stage III||Up to T3, N2, M0 or T4, any N, M0|
|Stage IV||Any T, any N, M1|
- Pancreatic head: 65% of cases
- Pancreatic body and tail: 15% of cases
- Diffuse: 20% of cases
Pancreatic exocrine tumors: originate from pancreatic acini and ducts 
Most common: ductal adenocarcinoma (95%)
- Altered ductal structures
- Cellular infiltration
- Less common
- Acinar adenocarcinoma (acinar cells produce digestive enzymes)
- Mucinous cystadenocarcinoma
- Most common: ductal adenocarcinoma (95%)
- Pancreatic endocrine tumors: originate from islet cells (See “Pancreatic neuroendocrine tumors” for details.)
The majority of pancreatic malignancies are located in the head of the pancreas and originate from epithelial cells within the tubules.
See “Subtypes and variants” for details on pancreatic cystic lesions and pancreatic neuroendocrine tumors.
- Focal pancreatitis 
- Pancreatic pseudocyst
- Metastasis: e.g., RCC (most common), breast carcinoma, bronchial carcinoma
- Ampullary cancer
- Lipoma 
The differential diagnoses listed here are not exhaustive.
General principles 
- Establish goals of care via shared-decision making.
- Multidisciplinary care is typically required.
- Treatment intent depends on:
- Tumor resectability
- Patient performance status and comorbidity profile
- Generally poor prognosis; all patients should be considered for clinical trials
- Provide supportive care and manage complications (e.g., biliary obstruction).
- See also “Principles of cancer care” for general information on treatment plans and goals of care.
Most patients are not candidates for surgery and require nonoperative management because they have inoperable tumors (∼ 80%), distant metastases, or are not medically fit for a major procedure. 
Approximately 10–20% of patients present with resectable tumors, 30–40% present with borderline resectable disease, and 50–60% present with locally advanced or metastatic disease. 
|Treatment of pancreatic cancer by disease stage|
|Treatment intent||Resectability status ||AJCC stage||Typical treatment approach|
|Potentially curative||Resectable disease|| || |
|Borderline resectable disease|| || |
|Usually palliative||Locally advanced unresectable disease|| || |
|Palliative||Metastatic disease|| || |
The only potentially curative treatment for pancreatic cancer is surgical resection, usually in combination with other treatments. Neither chemotherapy nor radiation therapy can be curative without surgery.
Potentially curable disease 
Curative treatment is primarily surgical and may involve neoadjuvant and/or adjuvant therapy.
- Primary surgical resection: recommended in patients with nonmetastatic disease who meet certain criteria.
- Neoadjuvant therapy prior to resection: for patients with features suggestive of metastatic disease and/or less favorable performance status
Surgical resection 
See also “Pancreatic surgery.”
Pancreatic head carcinoma: pancreaticoduodenectomy and lymphadenectomy
- Whipple procedure: resection of pancreatic head, distal stomach, duodenum, gallbladder, and common bile duct
- Traverso-Longmire procedure: pylorus-preserving pancreaticoduodenectomy 
- Reconstruction methods include enterostomy, Roux-en-Y, and Billroth-II.
- Pancreatic body and tail carcinoma: : Typically involves resection of the left side of the pancreas with splenectomy
Chemotherapy and radiotherapy for potentially curable disease 
Neoadjuvant therapy: to improve resectability
- Indication: considered in patients with a high likelihood of metastatic disease or margin-positive resection 
- Regimen: usually FOLFIRINOX or gemcitabine-based regimens, though no clear consensus exits 
Adjuvant therapy: to increase long-term survival
- Indication: all patients following surgical resection who did not receive preoperative treatment
- Regimen: up to 6 months of chemotherapy (e.g., mFOLFIRINOX) with or without chemoradiation
Following preoperative therapy, patients require full restaging to assess for resectability. 
Locally advanced and metastatic disease
Treatment intent is usually palliative. Patients with locally advanced disease may be able to undergo curative surgery if preoperative treatment leads to improved resectability; however, this is rare. 
Locally advanced disease
- Combination of chemotherapy (e.g., FOLFIRINOX), chemoradiotherapy, and/or stereotactic body radiation therapy
- Patients with a dramatic response to chemotherapy may be able to undergo surgical resection.
- The approach depends on ECOG performance status (ECOG PS), symptom burden, comorbidity profile, and the presence of actionable genomic alterations. 
- Regimens: e.g., FOLFIRINOX, nab-paclitaxel PLUS gemcitabin
Supportive care 
For general guidance on supportive care for cancer and/or treatment-related complications, see “Principles of cancer care” and “Overview of palliative medicine.”
Pain management 
Severe pain is common in the course of tumor progression. See “Treatment of pain” and “Pain management in palliative care” for additional guidance.
- Follow the WHO analgesic ladder and consider early consultation with a pain specialist.
- Anticipate side effects and consider interventions for their treatment and prevention (e.g., laxatives and antiemetics for patients who require opioids).
- Radiotherapy: Consider for patients with symptomatic metastases, especially to the brain and bones (rare).
Advanced interventions: Consider for patients with refractory abdominal pain. 
- Celiac ganglion block (celiac plexus neurolysis): EUS-guided transgastric puncture of the celiac ganglion with instillation of 98% ethanol to destroy the nerve tissue
- Thoracoscopic splanchnicectomy: unilateral or bilateral sectioning of the splanchnic nerve to interrupt pain-conducting nerve fibers
Cancer anorexia-cachexia syndrome 
- Obtain nutrition counseling.
- Consider nutritional supplements and appetite stimulants (e.g., megestrol acetate, dronabinol).
- Treat exocrine pancreatic insufficiency with pancreatic enzyme replacement.
Monitoring and follow-up 
Data to guide monitoring for recurrence and follow-up recommendations after curative treatment for pancreatic cancer is limited. The following recommendations are based on expert opinion and consistent with the 2016 American Society of Clinical Oncology (ASCO) guidelines. 
- Follow-up frequency: every 3–6 months for 2 years, then every 6–12 months
- Patient history and physical examination
- CA 19-9 levels if elevated at baseline
- Cross-sectional abdominal imaging (e.g., CT abdomen)
Lymphogenic and hematogenous metastases are often already present at the time of diagnosis.
- Early stage: liver, nearby lymph nodes
- Advanced stage: surrounding visceral organs (duodenum, stomach, colon), lungs
Management of GI complications 
Biliary obstruction: e.g., stenosis of the common bile duct
- ERCP with stent implantation (preferred)
Percutaneous transhepatic bile duct drainage (PTCD)
- Involves placement of an external drain that drains the bile into a collection bag.
- Consider if endoscopic access is impaired.
- Surgical bypass: consider in select patients when other measures fail or are not feasible.
Gastric outlet and/or duodenal obstruction
- Preferred: endoscopic stent placement
- Percutaneous endoscopic gastrostomy (or jejunostomy)
- Surgical bypass (e.g., gastroenterostomy)
- Cautious use of diuretics (e.g., spironolactone)
- Intermittent paracentesis or placement of a long term peritoneal drain
- Ileus: percutaneous endoscopic gastrostomy (PEG) tube as a relief tube
- Venous thromboembolism (VTE): See “Deep vein thrombosis” and “DVT prophylaxis” for details on prevention and management. 
- Disseminated intravascular coagulation (DIC)
Patients with pancreatic cancer are at a very high risk of VTE.
We list the most important complications. The selection is not exhaustive.
Very aggressive course 
- Overall 5-year survival rate: 10%
- 5-year survival rate of metastatic pancreatic cancer: ∼ 3%
- Median survival for patients who undergo successful resection: ∼ 18 months (5-year survival rate: ∼ 20%) 
Subtypes and variants
Pancreatic cystic lesions 
- Epithelium-lined cyst, filled with serous or mucous liquid
- Can be benign, precancerous, or cancerous
Clinical features: usually asymptomatic
- May cause abdominal pain or back pain
- Rarely, obstructive jaundice or features of ascending cholangitis (e.g., fever, sepsis) may develop.
- Diagnosis: most often found incidentally; on CT or MRI abdomen; can be followed by endoscopic investigations (e.g., EUS, ERCP) and tissue sampling (e.g., FNA)
Management: varies depending on radiological and pathological features (e.g., size, location, degree of cell dysplasia) and patient characteristics (e.g., symptoms, preoperative risk assessment) 
Offer surgical resection to patients with:
- High-risk features on imaging
- Pathology showing malignancy or high-grade dysplasia
- Worrisome symptoms (e.g., jaundice)
- Consider conservative management for asymptomatic individuals with low-risk lesions, e.g.:
- Offer surgical resection to patients with:
Pancreatic cysts are common in patients with von Hippel-Lindau syndrome. 
Benign lesions 
Benign lesions have low malignancy potential and are typically managed conservatively.
- Serous cystadenomas: typically appears as a honeycomb-like cluster of cystic lesions 
- Simple cysts (retention cysts): typically appear as a single well-defined, nonenhancing, unilocular cyst without mural nodularity or calcification 
Precancerous lesions 
Surgical resection is usually offered to good surgical candidates; conservative management can be considered in select cases.
- Intraductal papillary mucinous neoplasms (IPMNs): most common pancreatic cystic neoplasm; malignancy potential 20–80% 
- Mucinous cyst neoplasm: most commonly affects women; malignancy potential up to 25% 
- Solid pseudopapillary neoplasms: most commonly affects young women; malignancy potential 10–15% 
Main-duct IPMNs have the highest malignancy potential (up to 80%) and should be evaluated early for surgical resection (e.g., pancreaticoduodenectomy). 
Pancreatic neuroendocrine tumors (PNETs) 
See also “Overview of pancreatic neuroendocrine tumors” and dedicated articles on “Insulinoma” and “Gastrinoma.”
- Neuroendocrine tumors arising from endocrine cells in the pancreas (e.g., islet cells) that can secrete a variety of hormones
- Functional PNETs: secrete hormones; symptoms depend on the type of hormone secreted (e.g., insulinomas cause hypoglycemia)
- Nonfunctional PNETs: do not secrete enough hormones to cause symptoms; can produce local mass effect if large enough
- Malignancy potential varies widely.
- Insulinomas Gastrinomas
- Vasoactive intestinal peptide-producing tumors
- Pancreatic polypeptide-secreting endocrine tumors of the pancreas
- Surgical resection is typically offered for localized lesions and is often curative.
- Consider targeted therapy and/or serial imaging for unresectable or metastatic disease.
- Symptomatic therapy of functional PNETs (e.g., somatostatin analogues) depends on the hormone secreted and the severity of the symptoms.
Screening of asymptomatic individuals 
- Not recommended for average-risk individuals
- Consider periodic MRI and EUS for high-risk individuals, e.g.: 
- Patients with genetic syndromes that carry a high risk of pancreatic cancer, e.g., Peutz-Jeghers syndrome, hereditary pancreatitis
- First-degree relatives of individuals who have pancreatic cancer AND any of the following:
- ≥ 2 genetic relatives with pancreatic cancer
- Specific genetic markers (e.g., BRCA mutations)
- Hereditary cancer syndromes (e.g., Lynch syndrome)
There are no specific biomarkers for pancreatic cancer screening. Imaging is recommended in certain high-risk individuals.