Precision oncology has transformed cancer management by enabling treatment decisions to be guided not only by where cancer originates, but also by the molecular alterations driving its growth.
Next-generation sequencing (NGS) has become an important part of this shift. It allows simultaneous detection of a broad range of genomic alterations relevant to diagnosis, prognosis, and treatment selection.
The value of timely molecular profiling is particularly evident in stage IV non-small-cell lung cancer (NSCLC), where identifying actionable alterations can help guide the choice of biomarker-directed therapy.
For clinicians, however, access to molecular information is only part of the equation. The result also needs to arrive in time to influence the treatment decision.
From sequential testing to comprehensive molecular profiling
Traditional molecular testing often evaluates individual biomarkers using separate assays. Techniques such as immunohistochemistry, PCR and in-situ hybridisation continue to play essential roles, depending on the cancer and biomarker being assessed.
With a growing number of clinically relevant genomic biomarkers, however, sequential testing can require more tissue, laboratory resources and time.
Comprehensive molecular profiling refines tumor classification, identifies clinically significant biomarkers, and detects actionable mutations and resistance mechanisms that inform targeted therapy, immunotherapy, and clinical trial eligibility. Real-world data showed patients whose treatment is guided by genomic profiling consistently experience better survival outcomes than those managed without biomarker-directed therapy1.
Expanding applications across oncology
Tumour-agnostic therapies have highlighted the importance of understanding a cancer’s molecular characteristics alongside its anatomical origin.
In solid tumours, molecular testing can identify alterations relevant to targeted-treatment options and clinical trials.
Genomic information also contributes to the diagnosis and classification of hematological malignancies, risk assessment and treatment planning.
Liquid biopsy is another evolving application. Analysis of circulating tumour DNA can provide molecular information when tumour tissue is limited or difficult to obtain and can complement tissue-based testing. Plasma and tissue testing are not interchangeable in every clinical situation, and their use depends on the disease, assay and clinical context.
When the right answers arrive too late
The journey from specimen collection to reporting of results involves sample and library preparation, sequencing, bioinformatics, variant interpretation and reporting. Samples may also need to move between laboratories. Batch-based workflows and multiple manual hand-offs can extend the overall turnaround time. As molecular information becomes more relevant to treatment selection, turnaround time becomes increasingly important.
When genomic results are not available at the point of treatment selection, clinicians can face a difficult choice; wait for additional molecular information or begin empiric therapy. Waiting may not always be feasible but starting treatment before actionable driver alterations are known can affect the opportunity to select an appropriate biomarker-directed first-line therapy.
As an example, immunotherapy has shown limited benefit in many oncogene-driven NSCLCs and may increase the risk of adverse events when followed by certain targeted agents, emphasizing the importance of obtaining molecular results before treatment initiation1.
Rapid NGS seeks to address this challenge by shortening the entire sample-to-report pathway, rather than simply making sequencing faster. The goal is practical; to make actionable molecular information available early enough to support first-line treatment selection and reduce reliance on empiric treatment. 3,4 According to a study in Canada, upfront NGS may also improve healthcare efficiency by reducing sequential testing and associated diagnostic delays and resource use. 2
Bringing genomics closer to clinical teams
Workflow integration is creating opportunities to reconsider where genomic testing can be performed. Traditionally, much of this testing has been concentrated in specialized reference or centralized laboratories, where expertise, scale and established testing capabilities continue to play an important role.
Integrated workflows are also making in-house testing an option for appropriately equipped hospitals and diagnostic laboratories.
Centralised and in-house models need not be competing approaches; they are likely to coexist, depending on testing volumes, clinical needs, laboratory expertise, quality requirements, economics and available infrastructure.
An in-house NGS service requires labs to demonstrate analytical performance before patient testing, and maintain quality management across the pre-analytical, analytical and post-analytical phases. Validated bioinformatics, appropriate computational infrastructure, molecular-pathology expertise and ongoing quality assurance are integral to reliable testing.5,6
The broader objective is to integrate molecular information more effectively into the cancer-care pathway from selecting the right patients and obtaining high-quality samples to interpreting genomic findings and delivering clinically relevant results to the treating team at the right time.
Achieving this will require investment in laboratory infrastructure, quality systems, molecular pathology, bioinformatics and workforce development, alongside closer coordination between pathology, molecular diagnostics and clinical oncology.
As precision oncology continues to expand, the next challenge is not simply generating more genomic information. It is ensuring that clinically useful information reaches the treating team when it can still shape a decision. Rapid NGS is one part of that transition, bringing reliable molecular insights closer to the moment when clinicians and patients need to make treatment decisions.
Disclaimer: The views expressed in this article are those of Thermo Fisher Scientific and not necessarily ET Healthworld. The content is for informational and educational purposes only and is not medical advice or a recommendation of any test, product or therapy. Testing and treatment decisions should be made by qualified healthcare professionals based on individual circumstances and applicable product labelling. Product availability, regulatory status and intended use may vary by country. Molecular testing should not delay necessary care.
Reference:
- Scott JA, Lennerz J, Johnson ML, Gordan LN, Dumanois RH, Quagliata L, Ritterhouse LL, Cappuzzo F, Wang B, Xue M, Vasudevan A, Varughese P, Vaidya V, Gart M, Dorrow N, Gierman HJ, Choksi RJ. Compromised Outcomes in Stage IV Non-Small-Cell Lung Cancer With Actionable Mutations Initially Treated Without Tyrosine Kinase Inhibitors: A Retrospective Analysis of Real-World Data. JCO Oncol Pract. 2024 Jan;20(1):145-153. doi: 10.1200/OP.22.00611. Epub 2023 Aug 9. PMID: 37556776; PMCID: PMC10827288.
- Sheffield BS, Eaton K, Emond B, Lafeuille M-H, Hilts A, Lefebvre P, Morrison L, Stevens AL, Ewara EM, Cheema P. Cost Savings of Expedited Care with Upfront Next-Generation Sequencing Testing versus Single-Gene Testing among Patients with Metastatic Non-Small Cell Lung Cancer Based on Current Canadian Practices. Current Oncology. 2023; 30(2):2348-2365. https://doi.org/10.3390/curroncol30020180
- Smith RE, et al. Evaluation of outcomes in patients with stage IV non-small-cell lung cancer harboring actionable oncogenic drivers when treated before receipt of genomic test results without tyrosine kinase inhibitors. J Clin Oncol. 2022;40(16 Suppl):1530. (ASCO Annual Meeting abstract.)
- Kim JH, Yoon S, Lee DH, Jang SJ, Chun SM, Kim SW. Real-world utility of next-generation sequencing for targeted gene analysis and its application to treatment in lung adenocarcinoma. Cancer Med. 2021 May;10(10):3197-3204. doi: 10.1002/cam4.3874. Epub 2021 May 7. PMID: 33960703; PMCID: PMC8124124.
- Jennings LJ, Arcila ME, Corless C, Kamel-Reid S, Lubin IM, Pfeifer J, Temple-Smolkin RL, Voelkerding KV, Nikiforova MN. Guidelines for Validation of Next-Generation Sequencing-Based Oncology Panels: A Joint Consensus Recommendation of the Association for Molecular Pathology and College of American Pathologists. J Mol Diagn. 2017 May;19(3):341-365. doi: 10.1016/j.jmoldx.2017.01.011. PMID: 28341590. (https://pubmed.ncbi.nlm.nih.gov/28341590/)
- Clinical and Laboratory Standards Institute (CLSI). Human Genetic and Genomic Testing Using Traditional and High-Throughput Nucleic Acid Sequencing Methods. 3rd ed. CLSI guideline MM09. Clinical and Laboratory Standards Institute; 2023. (https://clsi.org/shop/standards/mm09/)
