Pancreatic%20cancer Diagnosis

• Goal is to identify and treat precursor lesions and prevent death from pancreatic cancer in high-risk familial patients
• 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

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)

• 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

Biopsy

• A tissue diagnosis, most commonly performed through an EUS-guided fine-needle aspiration (FNA), is generally required for patients starting neoadjuvant or palliative therapy
• Not mandatory for patients with high suspicion of pancreatic ductal adenocarcinoma and resection is planned as 1st-line treatment
• EUS with 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

• 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 surveillance, 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)

• Genetic testing for inherited mutations 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 molecular 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), amplifications (HER2) and/or mismatch repair (MMR) deficiency

Tumor-Node-Metastasis System for PC

• Developed by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC)