pancreatic%20cancer
PANCREATIC CANCER
Pancreatic cancer is malignancy arising from the pancreas.
It is the 13th most common cancer in the world, 10th most common in the United States, and 4th leading cause of cancer-related deaths in the United Stated and Europe.
Exocrine tumors account for 95% of malignant pancreatic disease.
It is more common in women.
The median age of occurrence is at 71 years old.

Pancreatic%20cancer Diagnosis

Screening

  • Goal is to identify and treat precursor lesions and prevent death from pancreatic cancer
  • Routine screening in asymptomatic individuals is not recommended

Recommendations of the 2019 International Cancer of the Pancreas Screening (CAPS) Consortium

  • Screening with EUS and/or MRI/MRCP is recommended in high-risk individuals:
    • Individuals with ≥1 1st-degree relative with PC who also has a 1st-degree relative with PC (familial pancreatic cancer kindred)
    • Carriers of a germline BRCA2, BRAC1, PALB2, ATM, MLH1, MSH2, or MSH6 gene mutation with ≥1 1st-degree relative with PC
    • Patients with Peutz-Jeghers syndrome (carriers of germline LKB1/STK11 gene mutation)
    • Carriers of a germline CDKN2A mutation
  • Surveillance tests are recommended annually in high-risk individuals if no abnormalities or non-concerning abnormalities are found on imaging and every 3-6 months if concerning abnormalities are found on imaging

Recommended Age to Start Screening:

  • Depends on the individual's family history and gene mutation status
    • Start at age 50 or 55 years or 10 years younger than the youngest affected blood relative in patients with familial PC kindred without a known germline mutation
    • Start at age 45 or 50 years or 10 years younger than youngest affected blood relative in carriers of BRCA2, ATM, PALB2, BRCA1, MLH1/MSH2 gene mutation
    • Start at age 40 years for carriers of CDKN2A gene mutation or if with Peutz-Jeghers syndrome
    • Start at age 40 years or 20 years after the 1st pancreatitis attack in patients with hereditary pancreatitis

Recommended Tests for Pancreatic Surveillance

  • Pancreatic imaging with MRI/MRCP and/or EUS for high-risk individuals
    • Pancreatic protocol CT may be performed for individuals unable to have MRI or EUS
  • CA 19-9 may be performed when possibility of PC is determined during pancreatic imaging
  • Fasting blood glucose and/or HBA1c determination is recommended for high-risk individuals to detect new-onset diabetes
    • New-onset diabetes in high-risk individuals should prompt further tests to determine presence of PC

Imaging

Imaging Procedures:

Computed Tomography (CT)

  • Preferred imaging study for the diagnosis and initial staging of pancreatic cancer
  • Multiphase pancreatic protocol CT with IV contrast in ≤3 mm thin cuts recommended
    • Noncontrast phase, contrast-enhanced arterial, pancreatic parenchymal, and portal venous phases should be included
  • For detection of pancreatic cancer: 74-98% accurate, 77-97% sensitive, 85-100% specific
  • For prediction of vascular invasion: 55-97% sensitive, 91-100% specific
  • For predicting resectability: 76-92% sensitive, 82-100% specific
  • Chest CT may be used to assess pulmonary metastasis before surgery
  • Should be done ≤4 weeks prior to surgery

Computed Tomography - Positron Emission Tomography (CT-PET)

  • Sensitivity for metastatic pancreatic cancer increases to 87% when combined w/ CT as compared to standard CT alone (57%)
  • May be used after formal pancreatic CT protocol to detect extra pancreatic metastases in high-risk patients

Magnetic Resonance Imaging (MRI)

  • Multiphase pancreatic protocol MRI is recommended as an alternative for the detection of smaller lesions when CT is contraindicated
  • Adjunct to CT in PC staging particularly for characterization of CT-indeterminate liver lesions
  • Effectively differentiates cancer and pancreatitis
  • Magnetic resonance cholangiopancreatography (MRCP)
    • Provides information on the patency of biliary and pancreatic ducts
    • Identifies vascular invasion

Endoscopic Ultrasound (EUS)

  • Used to identify nodal/vasculature involvement, suspected small lesions (<2 cm) not seen in CT/MRI, tumor size, and stage and resectability of disease
  • 86-96% accurate, 85-100% sensitive, 98% specific for pancreatic cancer
  • Preferred over CT/MRI for the detection of small tumors and differentiating cystic from solid lesions
  • Complementary to CT/MRI for staging purposes
  • May be used to distinguish between benign and malignant strictures or stenosis and to evaluate periampullary masses separating invasive from noninvasive lesions
  • Can better characterize cystic pancreatic lesions by aspiration of cystic contents for cytologic, biochemical and molecular analysis
  • Allows performance of fine-needle aspiration biopsy (FNAB) to confirm the presence of pancreatic cancer

Endoscopic Retrograde Cholangiopancreatography (ERCP)

  • Combines endoscopic and fluoroscopic procedures and is limited to therapeutic interventions 
  • Detects abnormalities/tumors in the pancreatic and bile ducts
  • Useful in identifying strictures within the ducts not diagnosed in other imaging modalities
  • Recommended for patients with jaundice or diagnosed on previous biopsy without evidence of metastatic disease and require biliary decompression
  • May also be used to place stents for decompression of biliary/pancreatic obstructions prior to surgery or chemotherapy

Laparoscopy

  • May be used to identify the stage of pancreatic cancer to rule out previous staging by imaging techniques
  • May detect peritoneal, capsular, or serosal implants and hepatic metastases
  • May be used selectively in patients with increased risk for disseminated disease

Laboratory Tests

Biopsy

  • EUS with fine-needle aspiration (FNA) is the recommended procedure for histologic confirmation of pancreatic cancer tumors
    • Preferred for its lower chances of peritoneal seeding, higher diagnostic yield, and confirmation of disease stage
    • 92% accurate, 84% accurate to refute or confirm negative CT-guided biopsy results
  • CT-guided FNA is an alternative when EUS is not available
    • May also be used to biopsy possible metastases
  • ERCP brushings are also an alternative for patients without mass in imaging but with biliary stricture
  • Core needle biopsy is recommended in patients with borderline resectable tumors in order to obtain adequate tissue for microsatellite instability (MSI) testing or genomic analysis 
  • Repeat biopsy is recommended before neoadjuvant therapy, prior to surgery, after stent placement, or in cases when previous biopsy is doubtful or inconclusive

Tumor Markers
  • Eg CA 19-9, carcinoembryonic antigen (CEA)
  • May be used to predict prognosis, recurrence rates, and outcome marker; also used to diagnose the cause of jaundice
  • Use for screening is not routinely done because of lack of specificity for pancreatic cancer
  • CA 19-9 is the most useful tumor marker for early detection and is recommended after neoadjuvant therapy, prior to surgery and postoperatively prior to adjuvant therapy to determine status of disease and treatment response
    • An abrupt drop in CA 19-9 levels postoperatively may indicate treatment success and good prognosis
    • CA 19-9 levels of ≥180 U/mL is associated with worse median survival rate (9 months)
    • CA 19-9 levels of ≤180 U/mL is associated with better median survival rate (21 months)

Other Tests
  • Germline testing using comprehensive gene panels for hereditary cancer syndromes is recommended when diagnosis of PC is confirmed
    • 4-8% of patients with pancreatic adenocarcinoma have germline mutations in BRCA1 or BRCA2
  • Tumor/somatic gene profiling for identification of uncommon mutations is recommended for patients diagnosed with locally advanced or metastatic disease and are candidates for anti-cancer therapy
    • Consider specific tests for fusions (eg ALK, NTRK), mutations (eg BRCA1/2, PALB2), and mismatch repair (MMR) deficiency

Staging

Tumor-Node-Metastasis System for PC

  • Developed by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC)
Primary Tumor (T) Categories
TX The main tumor cannot be assessed
T0 No evidence of a primary tumor
Tis Carcinoma in situ (very few tumors are found at this stage)
Includes intraductal papillary mucinous neoplasm with high-grade dysplasia, intraductal tubulopapillary neoplasm with high-grade dysplasia, mucinous cystic neoplasm with high-grade dysplasia and high-grade pancreatic intraepithelial neoplasia
T1 The cancer has not spread beyond the pancreas and is ≤2 cm (~0.75 inch) across
    T1a Tumor is ≤0.5 cm across
    T1b Tumor is >0.5 cm and <1 cm across 
    T1c Tumor is 1-2 cm across 
T2 The cancer has not spread beyond the pancreas but is >2 cm and ≤4 cm across
T3 The cancer is confined to the pancreas and is >4 cm across
T4 The cancer has extended further beyond the pancreas into nearby large blood vessels
Regional Lymph Nodes (N) Categories
NX Regional lymph nodes cannot be assessed
N0 Regional lymph nodes (lymph nodes near the pancreas) are not involved
N1 Cancer has spread to regional lymph nodes
N2 Cancer has spread to ≥4 regional lymph nodes 
Distant Metastasis (M) Categories
M0 The cancer has not spread to distant lymph nodes or to distant organs
M1 Distant metastasis is present
Stage Grouping for Pancreatic Cancer
Stage 0 (Tis, N0, M0) The tumor is confined to the top layers of pancreatic duct cells and has not invaded deeper tissues. It has not spread outside the pancreas.
Stage IA (T1, N0, M0) The tumor is confined to the pancreas and is ≤2 cm in size. It has not spread to nearby lymph nodes or distant sites.
Stage IB (T2, N0, M0) The tumor is confined to the pancreas and is >2 cm and ≤4 cm in size. It has not spread to nearby lymph nodes or distant sites.
Stage IIA (T3, N0, M0) The tumor is confined to the pancreas and is >4 cm in size. It has not spread to nearby lymph nodes or distant sites.
Stage IIB (T1–3, N1, M0) The tumor is confined to the pancreas and is <2 to >4 cm in size. It has spread to ≤3 nearby lymph nodes but not to distant sites.
Stage III (T1-3, N2, M0) The tumor is confined to the pancreas and is <2 to >4 cm in size. It has spread to ≥4 nearby lymph nodes but not to distant sites.
Stage III (T4, any N, M0) The tumor is growing outside the pancreas into nearby large blood vessels. It may or may not have spread to nearby lymph nodes. It has not spread to distant sites. 
Stage IV (any T, any N, M1) The cancer has spread to distant sites.
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