Mismatch Repair (MMR) or Microsatellite Instability (MSI) Biomarker Testing

Measure Specification

Detection of defective mismatch repair in colorectal carcinomas is important for detection of Lynch syndrome (hereditary nonpolyposis colorectal cancer syndrome [HNPCC]), which accounts for approximately 2 percent to 4 percent of all colorectal carcinomas and has clinical implications for treatment of the affected patient and family members. National Comprehensive Cancer Network (NCCN) recommends that all patients with a personal history of colon or rectal cancer should have MMR or MSI testing.

In the Molecular Biomarkers for the Evaluation of Colorectal Cancer guideline from the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology it is recommended that mismatch repair status testing in patients with colorectal cancers is necessary for the identification of patients at high risk for Lynch syndrome and/or prognostic stratification.

One of two different initial tests can be performed on colorectal specimens to identify individuals who might have Lynch Syndrome: 1) immunohistochemistry (IHC) for MMR protein expression, which is often diminished because of mutation; or 2) analysis for microsatellite instability (MSI), which results from MMR deficiency. NCCN guidelines state IHC and MSI on newly diagnosed colorectal and endometrial cancers regardless of family history to determine Lynch Syndrome, is cost effective and has been confirmed for colorectal cancer and endorsed by the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) working group at the CDC, the US Multi-Society Task Force on Colorectal Cancer, and the American Gastroenterological Association.

This measure is based on recommendations in an upcoming guideline regarding use of MMR/MSI testing in patients being considered for checkpoint inhibitor therapy (October 2022; see MMR/MSI Guideline for more information). Although recommendations have existed for screening colorectal cancer (see Biomarkers in CRC for more information) and endometrial cancer (see NCCN Guidelines for more information), universal testing remains elusive.

Data collected for these two cancer types in the Pathologists Quality Registry shows significant gap (performance rates of 71.05 percent with a standard deviation of 22.37 points and 76.63 percent with a standard deviation of 15.08 points respectively from 2020). Furthermore, only 42 percent of US-based practices gastroenterologists recommend universal MMR/MSI testing for colorectal cancer patients (Jain et al.

, 2019), and 50 percent of clinicians for endometrial cancer patients (Pan et al., 2018). Due to the recent nature of the recommendation for testing of gastric and small bowel cancer patients, rates of testing are difficult to ascertain, but a 2017 study showed that MMR/MSI testing was performed in only 51 percent of cases (Mathiak et al., 2017). A 2018 survey of clinicians found that 0 percent of respondents recommend universal testing of small bowel cancer cases (Pan et al.

, 2018). Testing for MMR/MSI will benefit patients and the health care system by making care more targeted. A better understanding of the genetic makeup of an individual’s cancer allows oncologists to design a personalized care plan, meaning patients get the right care faster. This will improve patients’ health faster and save the health care system wasted costs.

This measure contains one strata defined by a single submission criteria. This measure produces a single performance rate. For purposes of MIPS implementation, this procedure measure is submitted each time a procedure is performed during the performance period. The most advantageous quality data code (QDC) submitted will be used for performance.