Advanced Testing Methods Show Promise in Detecting Lung Cancer Biomarkers and Monitoring Disease

Advanced testing methods, including RNA-based assays and circulating tumor DNA (ctDNA) liquid biopsies, are transforming cancer detection and monitoring. RNA-based testing improves the identification of MET exon 14 skipping alterations in lung cancer, which are often missed by DNA-only methods. Meanwhile, ctDNA testing helps clinicians detect minimal residual disease, guide targeted therapies, and monitor recurrence. However, challenges remain, as ctDNA sensitivity is limited by low tumor burden and varies significantly across different cancer types.

ctDNA testing methodology

• ▪A multinational external quality assessment scheme showed a 98% success rate for tissue-based testing of MET exon 14 alterations across laboratories.
• ▪The success rate for liquid biopsy testing of MET exon 14 alterations in external quality assessment schemes improved from 37.5% in 2022 to 63% in 2024.
• ▪RNA-based testing can improve the detection and interpretation of MET exon 14 skipping alterations in non-small cell lung cancer patients compared to DNA-only approaches.
• ▪Circulating tumor DNA testing, also known as liquid biopsy, analyzes a patient's blood to detect DNA fragments from cancer cells.

Treatment decision guidance

• ▪Circulating tumor DNA testing serves as a supplement to the National Comprehensive Cancer Network guidelines rather than a stand-alone diagnostic tool.
• ▪Results from the BESPOKE CRC study found that stage II/III colorectal cancer patients who were minimal residual disease positive per ctDNA testing lived longer after receiving adjuvant chemotherapy.
• ▪Circulating tumor DNA testing can identify mutations like KRAS G12C or RAF to signify when to add specific targeted therapies to chemotherapy.

Patient anxiety management

• ▪A positive circulating tumor DNA test result indicates a more than 90% chance that a patient's cancer will recur.
• ▪Waiting for imaging tests can cultivate stress and delay treatment, whereas a simple blood draw for circulating tumor DNA testing can streamline decision-making.

Testing accuracy limitations

• ▪Circulating tumor DNA testing may fail to detect early-stage tumors that are less than 1 centimeter in diameter.
• ▪A study found that the circulating tumor DNA detection rate for prostate cancer is over 77%, compared to over 90% in other cancer types.
• ▪Detecting circulating tumor DNA is more challenging in patients who have kidney, prostate, and thyroid cancers.

Early cancer detection

• ▪Screening for circulating tumor DNA can be used to detect cancer early, before symptoms occur, and to monitor tumor growth.
• ▪A study found that detection of circulating tumor DNA markers was possible up to 2 years prior to a clinical diagnosis of colorectal cancer.

Tumor burden sensitivity

• ▪Circulating tumor DNA testing can prove inaccurate in cases where the patient does not have a high tumor burden.
• ▪Patients with a solitary liver metastasis may return a negative circulating tumor DNA test because there is not enough DNA in the bloodstream.

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