RAS testing for colorectal cancer patients is reliable in European laboratories that pass external quality assessment

Area of Science:

• Oncology
• Molecular Diagnostics
• Genetics

Background:

• Accurate KRAS and NRAS gene (exon 2, 3, and 4) wild-type status determination is crucial for metastatic colorectal cancer (mCRC) patients undergoing EGFR-targeting therapy.
• Significant variability exists in RAS testing methodologies, with recent introduction of more sensitive detection methods.
• Existing quality assessment data suggests considerable error rates in RAS testing.

Purpose of the Study:

• To evaluate the completeness and accuracy of RAS testing in European laboratories that have successfully completed external quality assessment (EQA).
• To assess the reliability of RAS testing for predicting anti-EGFR therapy efficacy in mCRC.

Main Methods:

• Thirty-one European laboratories that passed EQA were requested to submit materials from their ten most recent mCRC patients tested for RAS status.
• Submitted materials included isolated DNA, H&E stained tissue slides, and patient reports.
• Samples were re-evaluated using next-generation sequencing (NGS) in a reference laboratory.

Main Results:

• Reanalysis was possible for 274 out of 309 samples from 31 laboratories.
• One institute failed to perform complete RAS testing despite regulatory requirements.
• Seven discordant RAS testing results were identified (2% of 274 samples), with five leading to a different prediction of anti-EGFR therapy efficacy.

Conclusions:

• Oncologists can generally trust the quality of RAS testing from laboratories with good EQA performance.
• Awareness of laboratory EQA participation and performance is essential for clinicians selecting anti-EGFR therapies.
• EQA providers often publish lists of high-performing laboratories, aiding clinical decision-making.