What is the recommended screening method for individuals at high risk of pancreatic cancer?

Pancreatic Cancer Screening for High-Risk Individuals

For individuals at high risk of pancreatic cancer, screening should be performed using endoscopic ultrasonography (EUS) and/or MRI/MRCP (magnetic resonance cholangiopancreatography) at specialized high-volume centers with expertise in pancreatic diseases. 1

Who Should Be Screened

Screening is recommended for the following high-risk individuals:

1. Family history-based criteria:

   • Individuals with ≥3 affected blood relatives with pancreatic cancer, with at least one being a first-degree relative 2, 1
   • Individuals with ≥2 affected first-degree relatives with pancreatic cancer 2, 1
   • Individuals with two or more affected blood relatives with pancreatic cancer, with at least one first-degree relative 2

2. Genetic syndrome-based criteria:

   • All patients with Peutz-Jeghers syndrome (STK11 mutation), regardless of family history 2, 1, 3
   • Individuals with CDKN2A (p16) mutations and one affected first-degree relative 2, 1
   • BRCA1/BRCA2 mutation carriers with one affected first-degree relative 2, 1, 3
   • PALB2 mutation carriers with one affected first-degree relative 1, 3
   • ATM mutation carriers with one affected first-degree relative 1, 3
   • Lynch syndrome (MLH1/MSH2/MSH6) mutation carriers with one affected first-degree relative 1, 3
   • Individuals with hereditary pancreatitis (PRSS1 mutation) 3

When to Begin Screening

The timing for initiating screening varies by risk category:

• Standard high-risk individuals: Age 50 or 10 years younger than the youngest affected relative in the family, whichever comes first 1, 3
• CDKN2A mutation carriers: Age 40 or 10 years before earliest family diagnosis 1, 3
• PRSS1 mutation carriers (hereditary pancreatitis): Age 40 3
• STK11 mutation carriers (Peutz-Jeghers syndrome): Age 30-35 or 10 years before earliest family diagnosis 1, 3

Recommended Screening Methods

1. Primary screening modalities:

   • EUS and MRI/MRCP in combination (both modalities recommended) 2, 1, 3
   • These techniques are complementary - EUS offers the advantage of tissue sampling capability when needed 4

2. Additional testing:

   • Fasting blood glucose and/or HbA1c as part of screening protocol 1
   • CA19-9 for individuals with concerning features on imaging 1
   • CT is not recommended as a primary screening tool 2, 3
   • ERCP should not be used for screening 2

Screening Intervals and Management

1. Normal findings or non-concerning abnormalities:

   • Screening interval of 12 months 1, 3

2. Concerning findings:

   • Indeterminate lesions: Repeat imaging in 3-6 months 1, 3
   • High-risk lesions without immediate surgical plans: Repeat imaging within 3 months 3
   • Solid lesions: Additional CT recommended, ERCP not recommended 2
   • New-onset diabetes in high-risk individuals: Immediate evaluation 1, 3

3. Surgical management:

   • Surgery should only be offered to candidates who can tolerate the procedure 2
   • All pancreatic resections should be performed at high-volume specialty centers 2, 1, 3
   • Oncological radical resection for suspected pancreatic cancer 1
   • Partial pancreatectomy may be suitable for small suspected pancreatic cancers (≤1cm) 1

Targets of Screening

The primary goals of pancreatic cancer screening are to detect and treat:

• Stage I pancreatic cancer confined to the pancreas with negative margins 1, 3
• High-grade dysplastic precursor lesions (PanIN or IPMN with high-grade dysplasia) 1, 3

Important Considerations and Caveats

• Prophylactic pancreatectomy is not indicated in gene mutation carriers without any precursor lesion 1
• Genetic testing and counseling should be considered for all high-risk individuals 1, 3
• Participation in a registry or referral to a pancreatic center of excellence is recommended 3
• The diagnostic yield of screening is approximately 0.74 per 100 patient-years, with approximately 135 high-risk individuals needing to be screened to identify one high-risk lesion 5
• Screening yield appears to be greatest in relatives >65 years old (35%) compared to those 55-65 years (3%) and <55 years (3%) 6
• The limitations and potential risks of pancreatic cancer screening should be discussed with patients before initiating a screening program 3
• Screening should be discontinued when patients are more likely to die of non-pancreatic cancer-related causes or are not candidates for pancreatic resection 3

Standardized protocols and reporting templates are essential to enhance the quality of screening examinations, improve consistency of clinical management, and facilitate research 7.