Strategies for the successful implementation of plasma-based NSCLC genotyping in clinical practice

Genotyping is recommended for all patients with metastatic non-squamous non-small-cell lung cancers (NSCLC), both to enable patients to receive targeted therapies and to avoid therapies they are unlikely to benefit from. However, obtaining tumour biopsy material for genotyping is often challenging and is unfeasible in some patients, indicating the need to incorporate liquid biopsy approaches. In this Perspective, the authors provide guidance on how analysis of ctDNA from liquid biopsy samples in patients with metastatic NSCLC prior to first-line therapy has the potential to extend the benefits of genotyping to virtually all patients. Upfront tumour genotyping is now considered an essential step in guiding treatment decision-making in the management of patients with advanced-stage non-small-cell lung cancer (NSCLC) in light of the ever-expanding toolbox of targeted therapies and immune-checkpoint inhibitors. However, genotyping of tumour biopsy samples is not feasible for all patients and, therefore, genomic analysis of circulating tumour DNA (ctDNA) has emerged as a compelling non-invasive option. Current guidelines universally recommend genotyping and support the use of ctDNA testing in certain settings, although they often omit the detail necessary for integrating these tests into clinical care on an individual basis. In this Perspective, we describe the rationale, promise and challenges associated with ctDNA-based NSCLC genotyping and suggest a framework for the implementation of these assays into routine clinical practice. We also offer considerations for the interpretation of ctDNA genotyping results, which, particularly when using next-generation sequencing panels, can be nuanced. Through the addition of this new approach to clinical practice, we propose that oncologists might finally be able to utilize effective genotyping in nearly all patients with advanced-stage NSCLC.

Automated summary

Genotyping is crucial for patients with metastatic non-squamous NSCLC, and analyzing ctDNA from liquid biopsy samples offers the potential to extend the benefits of genotyping. Tumor genotyping guides treatment decisions for advanced-stage NSCLC patients, with ctDNA testing emerging as a key non-invasive option. Through the integration of ctDNA-based genotyping into routine clinical practice, effective genotyping may be utilized in nearly all patients with advanced-stage NSCLC.