Underutilization of Lynch syndrome screening in a multisite study of patients with colorectal cancer

Abstract

Purpose: The aim of this study was to examine Lynch syndrome screening of patients with metastatic colorectal cancer in integrated health-care-delivery organizations.

Methods: We determined the availability of Lynch syndrome screening criteria and actual Lynch syndrome screening in the medical records of 1,188 patients diagnosed with metastatic colorectal cancer between 2004 and 2009 at seven institutions in the Cancer Research Network.

Results: We found infrequent use of Lynch syndrome screening (41/1,188). Family history was available for 937 of the 1,188 patients (79%). There was sufficient information to assess Lynch syndrome risk using family history-based criteria in 719 of the 937 patients (77%) with family history documentation. In 391 individuals with a family history of a Lynch syndrome-associated cancer, 107 (27%) could not be evaluated due to missing information such as age of cancer onset. Eleven percent of patients who met the Bethesda criteria and 25% of individuals who met the Amsterdam II criteria were screened for Lynch syndrome. Recommended guidelines were adhered to during screening, but no testing method was preferred.

Conclusion: The information required for Lynch syndrome screening decisions is routinely collected but seldom used. There is a critical gap between collection of family history and its use to guide Lynch syndrome screening, which may support a case for implementation of universal screening guidelines.

Figure 1. Flow Diagram of Lynch Syndrome Screening Conducted Among Patients in the Study Sample

Abbreviations: MSI-L indicates Microsatallite Instability Low; MSI-S indicates Microsatellite Instability Stable, MSI-H indicates Microsatellite Instability High *Lynch Syndrome screening indicates any guideline-recommended combination of genomic microsatellite instability (MSI) and/or protein immunohistochemistry (IHC) tests, germline mutation analysis of MLH1, MLH2, MLH6, and PMS2 genes, as well as MLH1 hypermethylation studies and BRAF testing to detect sporadic MMR defects ^,, † Further testing is not indicated when tumors are MSI-L or MSI-S, or when all gene protein products are present on IHC because patients are assumed not to have Lynch Syndrome ^,,, ‡ Further testing is not indicated in the case of MLH1 methylation or BRAF v600E mutation because patients are assumed to not be at risk for Lynch Syndrome ^,,

Figure 2. Availability and completeness of family history information recorded in patient medical records

Abbreviations: CRC = colorectal cancer *No Family history information recorded (N=251) were not evaluated for Lynch Syndrome Risk † Total N=719 (out of 937 with family history documentation) were evaluated for Lynch Syndrome risk: “Family history unknown” (N=10), “No family history of colon cancer” (N=62), “Negative/noncontributory family history” (N=39), and “≥1 relative with CRC or Lynch-related cancer AGE NOT RECORDED” (N=107) could not be evaluated for Lynch Syndrome risk due to insufficient information.