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Published on: July 28, 2010
Underutilization of Guideline-Recommended Mismatch Repair/Microsatellite Instability Biomarker Testing in Advanced
David J Papke1, Neal I Lindeman1,2, Deborah Schrag3
1Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Background:
In 2017, DNA mismatch repair/microsatellite instability (MMR/MSI) testing was nationally recommended for advanced colorectal cancers based on favorable immune checkpoint inhibitor responses among patients with MMR-deficient/MSI-high tumors.
Methods:
Patients ages ≥20-years-old presenting with stage IV colorectal adenocarcinoma from 2010 to 2017 were identified from the National Cancer Database. 2017 was the latest year with available testing utilization data. Patient, tumor, socioeconomic, and care setting characteristics were evaluated for association with upfront MMR/MSI testing in 2017 using multivariable logistic regression and average adjusted predicted probabilities (%AAP).
Results:
Among 72,830 stage IV colorectal cancers, upfront MMR/MSI testing levels increased from 16.4% in 2010 to 56.4% in 2017. For patients diagnosed in 2017 (i.e., following national recommendations, n = 10,022), testing levels were lower for older patients (Padj < 0.001), and were independent of patients' race/ethnicity and insurance status. Patients from the poorest quartile of households received less testing [49.6%AAP, 99.9% confidence interval (CI) 45.5-53.7] than patients from the 3rd (56.9%AAP, 99.9% CI, 53.3-60.6; Padj < 0.001) or 4th quartiles (57.6%AAP, 99.9% CI, 54.3-60.9; Padj < 0.001). Although testing levels improved most at community programs, they remained lower in 2017 (46.6%AAP, 99.9% CI, 41.0-52.1) compared with academic/NCI-designated comprehensive cancer centers (62.8%AAP, 99.9% CI, 59.7-65.8; Padj < 0.001).
Conclusions:
Upfront MMR/MSI testing utilization for patients with advanced colorectal cancer has increased but there is still substantial need for optimization. Testing utilization disproportionately lagged for patients who were older, from the poorest quartile of households, or managed at community cancer programs.
Impact:
Our findings indicate opportunities for improving rates of MMR/MSI testing and reporting, possibly through incorporation into quality control and accreditation metrics.
Insights
DNA mismatch repair/microsatellite instability (MMR/MSI) testing increased for advanced colorectal cancer but lags for older, poorer patients and those in community programs. Optimization is needed for equitable access to this crucial diagnostic test.
Area of Science:
- Oncology
- Genetics
- Public Health
Background:
- National recommendations for DNA mismatch repair/microsatellite instability (MMR/MSI) testing in advanced colorectal cancer were established in 2017.
- Testing is crucial for identifying patients with MMR-deficient/MSI-high tumors who benefit from immune checkpoint inhibitors.
Purpose of the Study:
- To evaluate trends in upfront MMR/MSI testing utilization for stage IV colorectal cancer from 2010 to 2017.
- To identify patient, socioeconomic, and care setting characteristics associated with testing disparities.
Main Methods:
- Analysis of stage IV colorectal adenocarcinoma patients (≥20 years) from the National Cancer Database (2010-2017).
- Multivariable logistic regression and average adjusted predicted probabilities used to assess factors associated with MMR/MSI testing in 2017.
Main Results:
- Upfront MMR/MSI testing increased from 16.4% (2010) to 56.4% (2017).
- In 2017, testing was lower for older patients and those from the poorest quartile of households.
- Testing rates were significantly lower in community cancer programs compared to academic centers.
Conclusions:
- Despite increased utilization, upfront MMR/MSI testing for advanced colorectal cancer requires optimization.
- Disparities in testing persist based on age, socioeconomic status, and care setting.
