Dr Patel on Remaining Gaps in Biomarker Testing for Early-Stage Resected NSCLC

"In the early-stage setting, the [issue is] getting a quick answer for patients on EGFR and ALK [mutation status], as well as the lack of insurance approval generally for next-generation sequencing, which is often more expensive and often slower. Unbalance is the biggest hurdle we face."

Sandip P. Patel, MD, a professor of medicine in the Department of Medicine at the University of California, San Diego (UCSD) and a medical oncologist at the UCSD Moores Cancer Center, discussed the current gaps in biomarker testing for early-stage non–small cell lung cancer (NSCLC) and how these might influence eligibility for adjuvant targeted therapies. 

Patel shared these insights at the 2025 IASLC World Conference on Lung Cancer. Patel identified the biggest hurdle in early-stage testing as the challenge of balancing the need for swift answers regarding EGFR and ALK mutations with the typical lack of insurance approval for next-generation sequencing (NGS). Although NGS is often perceived as more expensive and slower, Patel argued it is more efficient from a tissue standpoint, considering the costs and time involved in repeated biopsies, especially since cell-free DNA does not form as effectively in early-stage disease.

Looking ahead, Patel suggested that digital pathology and AI-based algorithms could provide clues about the probability of specific mutations, which might then allow for rapid, single-gene cartridge-based testing or quicker NGS panels. However, he emphasized that insurance reimbursement for these advanced tests would be crucial. He also cautioned against the potential for a Pandora's box scenario, where broader NGS testing might reveal mutations, such as MET exon 14 skipping in a stage II patient, for which there is no established adjuvant setting treatment based on clinical trials.

For the current clinical landscape, Patel recommended prioritizing testing for EGFR, ALK, and PD-L1 in the early-stage setting, noting that if only one gene can be tested, EGFR is most important. He also pointed out that many ongoing clinical trials are exploring targeted therapy combinations in neoadjuvant, postoperative, or perioperative settings, all of which will require NGS. This remains a challenge because these methods are tissue-based in early-stage disease, where liquid biopsy does not perform as well as it does in the metastatic setting, Patel concluded.