What is the recommended pancreatic cancer screening approach for individuals with an Ataxia-Telangiectasia Mutated (ATM) mutation?

Pancreatic Cancer Screening for ATM Mutation Carriers

Pancreatic cancer screening is recommended for individuals with ATM mutations who have at least one first-degree relative with pancreatic cancer, using alternating MRI/MRCP and EUS annually beginning at age 50 or 10 years younger than the youngest affected relative, whichever comes first. 1

Eligibility Criteria for ATM Mutation Carriers

ATM mutation carriers have an increased risk of developing pancreatic cancer. However, not all ATM mutation carriers require screening. The criteria for pancreatic cancer screening in ATM mutation carriers are:

• Required: At least one first-degree blood relative with pancreatic cancer 1
• Starting age: Age 50 or 10 years younger than the youngest affected relative, whichever comes first 1
• Exception: ATM mutation carriers without a family history of pancreatic cancer are generally not recommended for routine screening 1

This recommendation is supported by the International Cancer of the Pancreas Screening (CAPS) Consortium, which specifically added ATM mutation carriers to their screening recommendations in their 2020 update 1.

Screening Protocol

The recommended screening approach includes:

• Primary screening modalities:

  • MRI/MRCP and EUS, typically alternating 1
  • Both modalities are considered complementary, with EUS having the advantage of allowing tissue sampling if needed

• Additional testing:

  • Fasting blood glucose and/or HbA1c should be routinely tested 1
  • CA19-9 should be used only when there are worrisome features on imaging 1

• Screening interval:

  • 12 months if no abnormalities or only non-concerning abnormalities are found 1
  • 3-6 months if concerning abnormalities are detected that don't immediately warrant surgery 1

Screening Goals

The primary goals of pancreatic cancer screening in high-risk individuals are to detect:

1. Stage I pancreatic cancer confined to the pancreas that can be resected with negative margins
2. Pancreatic cancer precursor lesions with high-grade dysplasia (PanIN or IPMN) 1

Implementation Considerations

Screening should ideally be performed:

• At high-volume centers with expertise in pancreatic diseases 1
• In the context of a research study when possible 1
• By multidisciplinary teams with experience in pancreatic cancer surveillance 1

Evidence Quality and Limitations

The recommendation for pancreatic cancer screening in ATM mutation carriers with a family history is based on expert consensus rather than randomized controlled trials 1. The CAPS Consortium used a modified Delphi approach to reach consensus, with 88% of experts agreeing that ATM mutation carriers with at least one affected first-degree relative should undergo surveillance 1.

It's important to note that the yield of pancreatic cancer screening in ATM mutation carriers under age 50 may be low 2, and the benefits, risks, and costs of pancreatic surveillance still need additional evaluation 1.

Genetic Testing Considerations

For individuals with a family history of pancreatic cancer, genetic testing may help identify those who would benefit from surveillance:

• Genetic testing should be performed in conjunction with genetic counseling 3
• Testing an affected family member is preferred when possible 3
• Multigene panel testing that includes ATM is recommended rather than single-gene testing 1

By following these evidence-based recommendations, clinicians can appropriately identify and screen ATM mutation carriers who may benefit from pancreatic cancer surveillance.