Molecular biomarker testing is enabling the delivery of precision oncology treatments, but developing processes and pathways for integrating these complex tests into practice can be challenging. Guidelines are necessary to help oncology stakeholders—not only pathologists, but also oncologists and laboratory personnel—make informed decisions about bringing new biomarker tests into practice and workflow. As the role of biomarkers in cancer diagnosis, prognosis, and treatment continues to grow, clinicians need access to reliable information on the appropriate use of molecular testing for the delivery of precision oncology therapies.

In response, the College of American Pathologist (CAP)is collaborating with the American Society of Clinical Oncology, the Association for Molecular Pathology, and Fight Colorectal Cancer to develop clinical guidelines for testing DNA mismatch repair (MMR) and microsatellite instability (MSI) status in patients with advanced solid tumor malignancies being considered for checkpoint inhibitor therapy. The guidelines will impact testing for patients with a range of cancers, including colorectal, endometrial, gastroesophageal, and small bowel.

CAP and its partner organizations are encouraging pathologists, oncologists, laboratory personnel, and allied health professionals to provide feedback on the draft recommendations, titled “MMR and MSI Testing in Patients Being Considered for Checkpoint Inhibitor Therapy,” to help ensure that the final recommendations are clinically practical. The panel will review and consider all comments received. The guideline manuscript will be submitted to Archives of Pathology & Laboratory Medicine later this year. All comments must be submitted by March 13 to be considered.

To better understand what these guidelines will mean to oncologists in particular, ACCCBuzz spoke to Timothy C. Allen, MD, JD, FCAP, Professor and Department Chair of Pathology at University of Mississippi Medical Center. Dr. Allen serves on the College of American Pathologists Board of Governors. He is the immediate past-president of the Pulmonary Pathology Society and a past-president of the Texas Society of Pathologists.

ACCCBuzz: How will these testing recommendations influence cancer care delivery for patients treated with checkpoint inhibitors? 

Dr. Allen: These guidelines, by providing some degree of standardization of MSI/MMR testing, should—as standardization typically does—increase the occurrence of, improve the timeliness of, and minimize the overall cost of MSI/MMR testing.

ACCCBuzz: What will these guidelines mean for front-line clinicians? 

Dr. Allen: These guidelines on the testing of MSI/MMR are primarily meant to guide the pathologist in the testing of cancers for which MSI/MMR testing has been shown beneficial. These guidelines should provide front-line clinicians peace of mind that the testing is being performed on their patients using the appropriate platforms, that the testing is interpreted accurately, and that any discordant or indeterminate results are dealt with correctly. Beyond that peace of mind, these guidelines hopefully will help some front-line clinicians better understand the molecular theory and reasoning behind testing. 

ACCCBuzz: How important is it for non-pathologist oncology professionals to understand these recommendations?

Dr. Allen: While written as guidelines for pathologists ordering MSI/MMR testing, these guidelines should also be shared with non-pathologist oncology professionals, including oncologists, nurse coordinators, etc., so those team members have a deeper understanding of the reason for MSI/MMR testing of a variety of cancers by various platforms. That will allow these professionals to better understand the reasons for, complexities of, and limitations of MSI/MMR testing. In turn, these professionals should be able to communicate more clearly with patients and their families, as well as payers, regarding the value of MSI/MMR testing in the variety of cancers for which testing is applicable.  

ACCCBuzz: Why is clinician feedback on this draft guidance so important?

Dr. Allen: Feedback is necessary from all stakeholders so any issue that the expert panel dealt with is fully vetted by the team who will actually be instituting the guidelines in practice. Although pathologist feedback will be extremely important, non-pathologist clinician feedback is no less vital, so the final guidelines are fully vetted, practical, and more likely to be accepted by all stakeholders. 

Read the CAP press release here.