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What’s required in ’23 for predictive marker tests

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Valerie Neff Newitt

September 2022—Beginning next year, two additional predictive marker tests will require enrollment in proficiency testing (PT), but for any predictive marker using immunohistochemistry or in situ hybridization, only laboratories that perform both staining and interpretation must participate in CAP-accepted PT.

For laboratories that perform only the staining or only the interpretation, but not both on site, alternative performance assessment will be required at least semiannually. Previously, staining-only laboratories were not required to perform proficiency testing or alternative assessment. For interpretation-only laboratories, it is a move away from proficiency testing to alternative performance assessment.

These requirements overall reflect “an urgent need to assess the quality of predictive marker testing because of the incredible importance of the decisions being made on these predictive markers leading to targeted therapies,” says Bradley S. Karon, MD, PhD, chair of the CAP Council on Scientific Affairs and professor of laboratory medicine and pathology at Mayo Clinic in Rochester, Minn. “But we’re doing it in a way that is going to allow us to assess the largest sources of variability or differences in quality without placing enormous burden on practices and labs to enroll in redundant Surveys.”

Avoiding that burden will come with the CAP’s shift from an interpretation-centric model for predictive marker testing to a staining-centric model, he says, “where the requirement for proficiency testing eventually falls mainly to the lab doing the staining and interpretation.” In a typical hub-and-spoke model where slides are stained and interpreted in a central (hub) laboratory, but this lab also sends stained slides to other labs (spokes) for interpretation, proficiency testing will now be required only for the hub laboratory, Dr. Karon says.

Under the new plan, the spoke labs that are performing interpretation only will not be required to enroll in a formal proficiency test, “because that model became burdensome and expensive” and couldn’t be expanded to accommodate new predictive markers, Dr. Karon says. Proficiency testing is still an option, but these laboratories can choose to perform another form of quality assurance, and the CAP is exploring new educational programs to meet the need. The programs would enable laboratories to assess not only the ability of pathologists to interpret but also the consistency of the interpretation among pathologists in a group or at a site.

The two predictive markers for which enrollment in proficiency testing will be required for the first time in 2023 are HER2 IHC in gastroesophageal adenocarcinoma and highly sensitive (hs) ALK in non-small cell lung cancer. The other two for which proficiency testing has been required for years are estrogen receptor and HER2 in breast cancer. “Other analytes deserve the same scrutiny as the breast biomarkers,” explains Andrew M. Bellizzi, MD, chair of the CAP Immunohistochemistry Committee and clinical professor in the Department of Pathology, University of Iowa Hospitals and Clinics.

The difficulty of IHC tests can vary, he notes. “Some are much more challenging, more finicky, in need of more attention.” Gastric HER2 and hsALK are two such tests, he says. “Because they are hard and the results are so critical to therapeutic decision-making, they demand more attention than the vast majority of analytes we look at by immunohistochemistry.” Of all the non-breast predictive markers, Dr. Bellizzi says, “these are the most problematic.”

The CAP’s plan for the oversight is found in the 2022 edition of the accreditation program checklists to be released next month, in COM.01520 PT and Alternative Performance Assessment for IHC, ICC, and ISH Predictive Markers. There it says the laboratory that performs IHC staining and interpretation must participate in CAP-accepted PT when it’s required, per the lab’s activity menu, and the stain-only and interpretation-only labs must perform alternative assessment at least semiannually.

It also says the laboratory that performs both predictive marker hybridization and ISH interpretation on site must participate in CAP-accepted proficiency testing. Labs that perform only one of the services must perform alternative assessment. These hybridization-only and ISH interpretation-only labs are not permitted to enroll in a formal proficiency testing program because, as the requirement notes, “participation in formal PT would constitute PT referral.”

Dr. Karon

For all other predictive marker testing performed by IHC, ISH, and immunocytochemistry for which the CAP doesn’t require proficiency testing, alternative performance assessment at least semiannually is required.

Dr. Bellizzi calls the lab’s activity menu “the most important piece in allowing us to move forward” with the PT requirement for gastric HER2 and hsALK.

The CAP has revised the activity menu so that it is aligned with the new proficiency testing and alternative performance assessment requirements for predictive marker testing using IHC. It now differentiates activities for each predictive marker to indicate clearly the staining and/or interpretation services the laboratory performs on site.

Not paying sufficiently close attention to the activity menu is a problem for some labs, says CAP checklist editor Lyn Wielgos, and an incomplete or incorrect activity menu is a common deficiency found when laboratories are inspected. “We also identify activity menu issues outside of the on-site inspection during follow-up after inspections or when working with laboratories on proficiency testing failures. Making sure the activity menu is correct is a key part in making sure this all makes sense and works,” she says of the requirements for predictive marker tests.

Says Dr. Bellizzi, “If labs are not telling us exactly what they are doing, then we’re limited in our ability to oversee.” Thus, the CAP is planning to offer education targeted to the updates to the activity menu and to the new proficiency testing requirements for predictive markers.

His advice: “Take a look at your activity menu, understand these three different ways to interface with the biomarker, understand what it means to do only staining, to do only interpretation, what it means to do staining and interpretation. If you don’t understand, ask for help and confirm that your activity menu is correct. If not, update it to make it as correct as possible.”

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