Longitudinal Liquid Biopsy for Circulating Tumor Cells in Metastatic Renal Cell Carcinoma

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In a study reported in the Journal of Clinical Oncology, Bootsma et al found that higher circulating tumor cell (CTC) enumeration trajectory identified through longitudinal liquid biopsy was associated with poorer survival in patients receiving immune checkpoint inhibitor treatment for metastatic renal cell carcinoma.

Study Details

The study involved 457 longitudinal liquid biopsies from 104 patients enrolled in a prospective cohort study and a phase II multicenter adaptive immunotherapy trial. A novel CTC capture and automated microscopy platform was used to profile CTC enumeration and expression of HLA I and PD-L1; given the diametric immunological roles of HLA I and PD-L1, their ratio (HP ratio) was assessed as a marker.

Key Findings

Patients with radiographic response to immune checkpoint inhibitor treatment had significantly lower CTC levels throughout treatment vs those with progressive disease (P = .035).

Patients receiving immune checkpoint inhibitor treatment with annual rate of change in CTC number in the top quartile for the cohort (> 0.12 CTCs/mL annually) had significantly shorter overall survival vs those with annual rate of change in the lower three quartiles (median = 17.2 months vs 21.1 months; hazard ratio [HR] = 5.9, 95% confidence interval [CI] = 1.9–18.7, P < .001).

Throughout treatment, the log10 HP ratio decreased in patients receiving immune checkpoint inhibitor treatment (slope = –0.10548, P = .0671) but not in patients receiving tyrosine kinase inhibitor treatment (slope = 0.012, P = .821). Patients with log10 HP ratio trajectory in the top quartile (≥ 0.0012 annually) had significantly shorter overall survival vs those with trajectories in the bottom three quartiles (median = 18.35 months vs 21.22 months; HR = 4.8, 95% CI = 1.5–15.3, P = .003).

The investigators concluded, “In the first large longitudinal CTC study in metastatic renal cell carcinoma to date to our knowledge, we identified the prognostic importance of CTC enumeration and the change over time of both CTC enumeration and the HP ratio. These insights into changes in both tumor burden and the molecular profile of tumor cells in response to different treatments provide potential biomarkers to predict and monitor response to immunotherapy in metastatic renal cell carcinoma.

Shuang G. Zhao, MD, MSE, of the Department of Human Oncology, Carbone Cancer Center Circulating Biomarker Core, University of Wisconsin, Madison, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by grants from the National Institutes of Health and National Cancer Institute, a Brian Mullins Renal Cell Cancer Research Award, and others. For full disclosures of the study authors, visit

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