Liquid Biopsy in Lung Cancer: Ready for Prime Time!

By Miguel Garcia-Pardo and Natasha B. Leighl

Liquid biopsies have emerged as a practical tool for genotyping circulating tumor DNA (ctDNA) in plasma. In patients with newly diagnosed NSCLC, knowledge of molecular alterations is essential for treatment decision-making. While tissue genotyping remains the gold standard, testing delays and insufficient tissue samples have led to growing interest in liquid biopsy as a complementary method of molecular diagnosis. In the recent International Association for the Study of Lung Cancer consensus, liquid biopsy is recommended for patients with advanced NSCLC in one of three ways: 1. as sequential testing, after tissue testing fails or when tissue is insufficient; 2. as complementary testing, initiated at the same time as tissue testing; and 3. as a plasma-first approach, when there is insufficient tissue or limited time for testing.

Barriers to broad uptake of liquid biopsy in routine practice include cost. In our recent cost-effectiveness analysis, published in Therapeutic Advances in Medical Oncology (Ezeife et al. Ther Adv Med Oncol. 2022 Jul 26;14:17588359221112696), the use of liquid biopsy alongside tissue testing for molecular profiling in selected advanced non-squamous NSCLC patients did not increase overall costs. The addition of plasma testing led to greater detection of actionable alterations and more patients receiving appropriate targeted therapy. The majority of cost savings resulted from more patients accessing targeted therapy instead of the inappropriate use of more costly and less effective chemo-immunotherapy.

Moving the use of liquid biopsy even earlier in the lung cancer diagnostic pathway, i.e. a plasma-first approach, may also improve patient outcomes. In a recent pilot study published in Therapeutic Advances in Medical Oncology, we demonstrated that a “plasma-first” approach in patients with suspected advanced lung cancer undergoing diagnostic work up led to shorter time to treatment and increased detection of actionable molecular alterations (Garcia-Pardo et al Ther Adv Med Oncol. 2022 Sep 20;14:17588359221126151). Time to treatment initiation in patients with advanced lung cancer was significantly improved by using ‘plasma first’ compared to an historical control using tissue (32 days versus 62 days, p<0.01). Time to treatment was shortened for all patients, even if targetable alterations were not identified, using a plasma-first approach.

While this is a promising strategy to improve patient access to treatment, the impact of the “plasma-first” approach on patient quality of life, survival and cost remains unclear. For example, despite the radiological findings suggesting a lung cancer, 10% of patients had primary cancers other than lung cancer, highlighting the importance of tissue biopsy for diagnosis and pathologic subtyping. Furthermore, “plasma-first” does not mean “plasma only”. In 2022, tumor biopsy is still required for lung cancer diagnosis, pathologic subtyping, and PD-L1 assessment in both advanced and early stage NSCLC. A small number of patients will require tumor tissue profiling to identify their alteration, given the lower sensitivity of plasma testing, and others may benefit from a complementary testing approach. In healthcare systems with constrained resources and delayed time to diagnosis, tissue biopsy and molecular testing, our findings suggest that patients are better served using a plasma-first approach. Even if plasma testing is non-informative, requiring reflex tissue testing, this approach may yield faster molecular results and shorter time to targeted treatment for patients.

Liquid biopsy for molecular genotyping in advanced NSCLC is ready for prime time, and can facilitate faster access to molecular results and optimal therapy. In selected populations, it can also be implemented without increasing overall system costs.

Learn more:
The economic value of liquid biopsy for genomic profiling in advanced non-small cell lung cancer
Doreen A. Ezeife, Eldon Spackman, Rosalyn A. Juergens, Janessa J. Laskin, Jason S. Agulnik, Desiree Hao, Scott A. Laurie, Jennifer H. Law, Lisa W. Le, Lesli A. Kiedrowski, Barbara Melosky, Frances A. Shepherd, Victor Cohen, Paul Wheatley-Price, Rachel Vandermeer, Janice J. Li, Roxanne Fernandes, Aria Shokoohi, Richard B. Lanman, and Natasha B. Leighl
First Published July 26, 2022
DOI: 10.1177/17588359221112696
Therapeutic Advances in Medical Oncology

Plasma-first: accelerating lung cancer diagnosis and molecular profiling through liquid biopsy
Miguel Garcia-Pardo, Kasia Czarnecka, Jennifer H. Law, Alexandra Salvarrey, Roxanne Fernandes, Jason Fan, Lucy Corke, Thomas K. Waddell, Kazuhiro Yasufuku, Laura L. Donahoe, Andrew Pierre, Lisa W. Le, Noor Ghumman, Geoffrey Liu, Frances A. Shepherd, Penelope Bradbury, Adrian Sacher, Tracy Stockley, Prodipto Pal, Patrik Rogalla, Ming Sound Tsao, and Natasha B. Leighl
First Published September 20, 2022
DOI: 10.1177/17588359221126151
Therapeutic Advances in Medical Oncology

About the authors

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Dr. Miguel Garcia-Pardo is a medical oncologist in the Department of Medical Oncology, Hospital Universitario Ramón y Cajal, Madrid and recent Fellow from the Princess Margaret Cancer Centre Thoracic Oncology Program. During COVID, he and the Princess Margaret Thoracic team demonstrated that liquid biopsy can improve access for patients to targeted therapy and shorten wait times for molecular diagnosis and treatment.

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Dr. Natasha Leighl leads the lung medical oncology team at the Princess Margaret Cancer Centre, where she and colleagues across Canada have worked to demonstrate that liquid biopsy improves lung cancer patient access to precision medicine and, in selected populations, does not increase overall costs of care in the public system.