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Disparity in Microsatellite Instability Testing Suggests Need to Close Socioeconomic Access Gaps

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NEW YORK – Despite the fact that microsatellite instability and DNA mismatch repair testing is now considered standard of care for Lynch syndrome diagnosis, colorectal cancer prognosis, and guiding tissue-agnostic treatment decisions, cancer patients aren't getting equitable access to this analysis, new research shows.

The study, presented earlier this month at a virtual conference on health disparities hosted by the American Association for Cancer Research, suggested that older Americans, men, and those of black, non-Hispanic ancestry are all less likely than others to receive microsatellite instability and DNA mismatch repair deficiency testing for colorectal cancer, even as these biomarkers have become more and more established in the treatment of CRC and across tumor types.

Presenting the results, Bryan Iorgulescu, an instructor of pathology at Brigham and Women's Hospital, said that the data further showed that insurance status and other factors, such as the type of hospital or care center a patient was diagnosed in, also contributed to disparate use of these crucial biomarkers. As such, the analysis points to potential avenues for filling access gaps and ensuring more equitable implementation of this growing arm of precision oncology, he said.

Although biomarker testing rates in colorectal cancer have risen in recent years, prior studies suggest that significant numbers of patients may still miss out on current, guideline-backed care.

For example, a paper published last December by researchers from data analytics company Cota Healthcare and liquid biopsy testing firm Guardant Health found that only 40 percent of metastatic colon cancer patients diagnosed between 2013 and 2017 were getting tested for predictive biomarkers recommended in guidelines, suggesting that many are losing out on the chance to receive precision therapies.

MSI and MMR defects have been included in guidelines for many years as a prognostic markers for colorectal cancer and for assessing patients' risk for the hereditary cancer condition Lynch syndrome. More recently, the same tests have also become standard tools for identifying colorectal patients eligible for immune checkpoint inhibitors.

In 2017, MSI/MMR testing also facilitated the first tissue-agnostic US Food and Drug Administration approval of a drug, pembrolizumab (Merck's Keytruda), as a treatment for MSI-high or MMR-deficient advanced solid tumors.

In light of the growing importance of MSI/MMR testing as a prognostic and predictive tool beyond colorectal cancer, Iorgulescu and his coauthor, Harvard Medical School fellow Nayan Lamba, hoped to further explore the factors that play a role in whether patients have access to this assessment. 

In particular, they wanted to fill data gaps in earlier studies. For example, with only 19 percent of its cohort being nonwhite, the Cota group was unable to make statistically significant conclusions about the impact of race on genotyping rates, though the authors stressed that this should be further explored in larger, more diverse cohorts.

In their analysis presented at the AACR meeting this month, Iorgulescu and Lamba pulled records from the National Cancer Database for 45,326 patients age 20 and older presenting with newly-diagnosed histopathologically confirmed stage IV colorectal adenocarcinoma between 2010 and 2016. These records also had data on whether or not patients received MSI/MMR testing.

The team analyzed patients’ demographic, socioeconomic, and care setting characteristics against their MSI/MMR testing status.

Only 26.5 percent of the patients received MSI/MMR testing over the six years, with testing rates increasing from 14.4 percent in 2010 to 41.1 percent in 2016.

Overall, patients who were older, male, or of Black non-Hispanic race or ethnicity were less likely to receive testing than others.

Patients who were either uninsured or had Medicaid or Medicare were also significantly less likely to be tested. And similar to what the Cota researchers saw in their study, the place a patient was diagnosed and treated also influenced their chances of getting tested. Individuals diagnosed at community or comprehensive community cancer programs were significantly less likely to be tested compared to those seen at an academic medical center or within an NCI-comprehensive cancer program.

Other research presented at the AACR meeting revealed similar patterns of access inequity. For example, NCI fellow Brittany Gardner used data from the National Survey of Precision Medicine in Cancer Treatment, the first nationally representative sample of oncologists practicing in the US, to investigate the availability of genomic testing resources.

She and her colleagues found that a higher proportion of academic than non-academic practices had genomic testing resources. The same was true of multi-specialty groups compared to single-specialty groups, and solo practices and urban practices versus rural practices, illustrating an "unequal distribution of genomic testing resources for cancer treatment by practice type and rurality."

According to Iorgulescu, he and his colleagues are continuing to investigate whether the various disparities they identified could be relieved simply by addressing the infrastructure inequity captured by Gardner's survey, or, alternatively, if there are issues specific to Black individuals or the elderly that require independent intervention.

In the meantime, the findings already highlight opportunities for improving access, at least in terms of socioeconomic and care setting barriers, according to the team's poster.

Iorgulescu didn't cite specific interventions but said that clearer standards for testing would help that can be used as a benchmark for determining if institutions are providing appropriate care.

"With respect to MSI/MMR testing for patients with advanced cancers who are being considered for checkpoint inhibitor therapy, an important step to improving testing rates is the development of evidence-based guidelines and recommendations to help inform pathologists and clinicians about the indications, best practices, and effective modalities for testing," Iorgulescu said in an email.

"Fortunately, such efforts are already underway jointly by the College of American Pathologists, American Society of Clinical Oncology, and Association for Molecular Pathology," he added.

Going forward, Iorgulescu argued, the type of analysis he reported at the AACR meeting should be done across the field of precision oncology. "More research into the practice patterns of molecular diagnostic testing … will permit us to better identify and close any gaps in appropriate testing," he said.

An important first step has been the incorporation of molecular testing data into national cancer databases, which is allowing Iorgulescu's team to examine testing patterns beyond MSI/MMR. For example, they're now looking at the access that glioblastoma patients have to MGMT promoter methylation testing.

Ensuring that these databases keep pace with the advances in precision oncology and collect clinically relevant molecular testing data will be crucial moving forward, Iorgulescu said.

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