Next-Generation Sequencing (NGS) Methods Show Superior or Equivalent Performance to Non-NGS Methods on <i>BRAF</i>, <i>EGFR</i>, and <i>KRAS</i> Proficiency Testing Samples.

Abstract

There has been a rapid expansion of next-generation sequencing (NGS)-based assays for the detection of somatic variants in solid tumors. However, limited data are available regarding the comparative performance of NGS and non-NGS assays using standardized samples across a large number of laboratories. To compare the performance of NGS and non-NGS assays using well-characterized proficiency testing samples provided by the College of American Pathologists (CAP) Molecular Oncology Committee. A secondary goal was to compare the use of preanalytic and postanalytic practices. A total of 17 343 responses were obtained from participants in the <i>BRAF</i>, <i>EGFR</i>, <i>KRAS</i>, and the Multigene Tumor Panel surveys across 84 different proficiency testing samples interrogating 16 variants and 3 wild-type sequences. Performance and preanalytic/postanalytic practices were analyzed by method. While both NGS and non-NGS achieved an acceptable response rate of greater than 95%, the overall performance of NGS methods was significantly better than that of non-NGS methods for the identification of variants in <i>BRAF</i> (overall 97.8% versus 95.6% acceptable responses, <i>P</i> = .001) and <i>EGFR</i> (overall 98.5% versus 97.3%, <i>P</i> = .01) and was similar for <i>KRAS</i> (overall 98.8% and 97.6%, <i>P</i> = .10). There were specific variant differences, but in all discrepant cases, NGS methods outperformed non-NGS methods. NGS laboratories also more consistently used preanalytic and postanalytic practices suggested by the CAP checklist requirements than non-NGS laboratories. The overall analytic performance of both methods was excellent. For specific <i>BRAF</i> and <i>EGFR</i> variants, NGS outperformed non-NGS methods and NGS laboratories report superior adherence to suggested laboratory practices.