Pancreatic cancer

Last updated: May 27, 2022

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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 [1][2]
  • Incidence
    • ∼ 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 [3][4]
    • African Americans
    • Individuals of Jewish ancestry

Epidemiological data refers to the US, unless otherwise specified.

Exogenous risk factors [5][6][7]

Endogenous risk factors [5][8]

In most cases, there are no early symptoms suggestive of pancreatic cancer. [9]

Constitutional symptoms

  • Poor appetite
  • Weight loss
  • Weakness

Gastrointestinal symptoms

Hypercoagulability

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.

Approach [10][11][12][13]

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”). [14]

Pancreatic incidentalomas should be investigated early and evaluated for curative resection.

Initial diagnostic imaging [12][16][17]

Used to identify potentially malignant lesions and evaluate for resectability

Routine laboratory studies [11][16][19]

Findings are variable and nonspecific but may show abnormalities caused by pancreatic cancer or related complications.

Diagnostic confirmation [12][16][20][21][22]

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.

Adjunctive investigations

  • MRCP
    • Typically used to rule out choledocholithiasis and assess if biliary decompression is indicated
    • Can be used adjunctively to evaluate local tumor extension [22][23]
  • ERCP: usually used when biliary decompression is indicated
  • Tumor markers: not recommended for diagnosis or screening ; [10][16][18]
    • CA 19-9
      • Prognostic marker [16]
      • Marker of cancer progression and response to therapy
    • CEA (less specific): may be used as an adjunct to CA 19-9 as a diagnostic and prognostic marker [24]

Imaging for preoperative staging [12][13]

Required to assess the extent of the tumor, the involvement of local key vascular structures, and to identify metastatic disease

  • Intraabdominal and pelvic staging: CT abdomen and pelvis (with IV and PO contrast, including pancreas-specific triphasic protocol) or MRI (including MRCP)
  • Thoracic staging: CXR or CT chest [12][25][26]

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 [27][28]
TNM classification
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
M1 Distant metastases
Staging groups
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

Location [29]

Cell origin

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.

The differential diagnoses listed here are not exhaustive.

General principles [12][34][35]

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. [12]

Approach [11][12][16][34][36]

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. [16]

Treatment of pancreatic cancer by disease stage
Treatment intent Resectability status [11][12][37] AJCC stage Typical treatment approach
Potentially curative Resectable disease
  • Stage I or II
Borderline resectable disease
  • Stage II or III
Usually palliative Locally advanced unresectable disease
  • Stage III
Palliative Metastatic disease
  • Stage IV
  • Combination chemotherapy; regimens vary depending on the patient's general condition and the presence of actionable genomic alterations.

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 [12]

Curative treatment is primarily surgical and may involve neoadjuvant and/or adjuvant therapy.

Approach

  • 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 [16][38][39]

See also “Pancreatic surgery.”

Chemotherapy and radiotherapy for potentially curable disease [12][40][41]

  • Neoadjuvant therapy: to improve resectability
    • Indication: considered in patients with a high likelihood of metastatic disease or margin-positive resection [12]
    • Regimen: usually FOLFIRINOX or gemcitabine-based regimens, though no clear consensus exits [40]
  • 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. [12]

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. [42]

Supportive care [12][16][34]

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 [12][34][35]

Severe pain is common in the course of tumor progression. See “Treatment of pain” and “Pain management in palliative care” for additional guidance.

  • Pharmacotherapy
  • Radiotherapy: Consider for patients with symptomatic metastases, especially to the brain and bones (rare).
  • Advanced interventions: Consider for patients with refractory abdominal pain. [43]

Cancer anorexia-cachexia syndrome [12][34][42]

Monitoring and follow-up [44]

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. [12]

  • Follow-up frequency: every 3–6 months for 2 years, then every 6–12 months
  • Follow-up evaluation

Metastasis

Lymphogenic and hematogenous metastases are often already present at the time of diagnosis.

Management of GI complications [34][45][46]

Thromboembolic disease

Patients with pancreatic cancer are at a very high risk of VTE.

Others

We list the most important complications. The selection is not exhaustive.

  • Very aggressive course [1]
  • Median survival for patients who undergo successful resection: ∼ 18 months (5-year survival rate: ∼ 20%) [47]

Pancreatic cystic lesions [48][49][50][51][52]

  • Description
    • Epithelium-lined cyst, filled with serous or mucous liquid
    • Can be benign, precancerous, or cancerous
  • Clinical features: usually asymptomatic
  • 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) [52]
    • Offer surgical resection to patients with:
    • Consider conservative management for asymptomatic individuals with low-risk lesions, e.g.:
      • Serial MRI (e.g., annually)
      • Tissue sampling (e.g., EUS with FNA) of lesions that develop suspicious radiological features
      • Referral for surgical resection in patients with worrisome pathology

Pancreatic cysts are common in patients with von Hippel-Lindau syndrome. [53]

Benign lesions [54]

Benign lesions have low malignancy potential and are typically managed conservatively.

  • Serous cystadenomas: typically appears as a honeycomb-like cluster of cystic lesions [50]
  • Simple cysts (retention cysts): typically appear as a single well-defined, nonenhancing, unilocular cyst without mural nodularity or calcification [51]

Precancerous lesions [52][54][55][56]

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% [54][57]
  • Mucinous cyst neoplasm: most commonly affects women; malignancy potential up to 25% [50]
  • Solid pseudopapillary neoplasms: most commonly affects young women; malignancy potential 10–15% [58]

Main-duct IPMNs have the highest malignancy potential (up to 80%) and should be evaluated early for surgical resection (e.g., pancreaticoduodenectomy). [54]

Pancreatic neuroendocrine tumors (PNETs) [59][60]

See also “Overview of pancreatic neuroendocrine tumors” and dedicated articles on “Insulinoma” and “Gastrinoma.”

Screening of asymptomatic individuals [14][61]

There are no specific biomarkers for pancreatic cancer screening. Imaging is recommended in certain high-risk individuals. [14]

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