Liquid Biopsies Show Promise but Face Key Challenges in Older Adults

Key Takeaways

• Liquid biopsies offer a less invasive, potentially safer tool for cancer diagnosis and monitoring in older adults, supporting personalized care across detection, treatment selection, and disease tracking.
• A review of 115 studies highlights promising clinical applications but emphasizes the need to incorporate geriatric factors like frailty, comorbidities, and functional status.
• Age-related biological changes, including increased cell-free DNA and clonal hematopoiesis, can cause false positives, underscoring the need for better validation before routine use.

Liquid biopsies could become a key tool for more personalized cancer care in older adults, but age-related biological changes must be better understood before the approach can be used reliably in routine practice, according to study results published in npj Precision Oncology.

As cancer incidence and mortality rise sharply with age, researchers say there is growing need for diagnostic and monitoring strategies that account not only for tumor biology but also for frailty, comorbidities, functional status, and social factors. Liquid biopsies, which analyze tumor-related material in blood or other body fluids, may offer a less invasive alternative to tissue biopsy for this population.

“In this comprehensive review, SIOG Translational Research Working Group—comprising geriatricians, medical oncologists, hematologists, surgical oncologists, radiation oncologists, nurses, and allied health professionals as well as a patient advocates—aims to evaluate the current evidence on liquid biopsy applications for older adults with cancer, including their diagnostic accuracy, prognostic value, and clinical applications,” explained the authors.

Researchers examined 115 full-text publications identified through a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided search of PubMed and Embase covering the 15 years before November 1, 2024. The included studies focused on clinical and translational applications of circulating tumor DNA, circulating tumor cells, extracellular vesicles, RNA-based markers, and other -omics approaches in cancer diagnosis, staging, treatment, and prognosis, provided they included age-related patient data.

The authors found that liquid biopsies may be especially attractive for older adults because repeated blood draws are generally safer and more acceptable than invasive tissue biopsies, particularly in frail patients or those with multiple comorbidities. Potential uses include earlier diagnosis, treatment selection, response monitoring, detection of minimal residual disease, and identification of resistance mutations. The review also notes that biomarker-guided therapies have already shown strong response rates in advanced cancers, including osimertinib in epidermal growth factor receptor (EGFR)-mutant non–small cell lung cancer at 80%, alectinib in ALK-positive disease at 83%, and entrectinib and crizotinib in ROS1 fusion-positive disease at 77% and 72%, respectively.

At the same time, the review underscores major limitations in older populations. Healthy aging itself can raise cell-free DNA levels, while clonal hematopoiesis of indeterminate potential becomes increasingly common with age, affecting more than 10% of adults older than 70 years and nearly 20% of those older than 90. These changes can create false-positive results by making non-tumor mutations appear cancer-related. In one study of 124 patients with cancer, more than half of the mutations detected in cell-free DNA were also found in white blood cells.

“Clarifying the convergence of clinical and molecular aging markers may ultimately enhance person-centered cancer care in older adults,” concluded the study authors.

Reference

Zhao Y, Herrera-Caceres JO, Nobes J, et al. Liquid biopsies in precision oncology for older adults with cancer. NPJ Precis Oncol. 2026;10(1):123. doi:10.1038/s41698-026-01285-5