Urinary markers in treatment monitoring of lung cancer patients with bone metastasis

Abstract

Background: Bone metastasis remains critical for advanced stage non-small cell lung cancer (NSCLC)—a disease that is challenging to manage. Urinary markers present opportunities for non-invasive testing. Methods: Urine specimens were collected from patients prior to treatment. Urinary cell-free DNA was subsequently purified from these samples. To address the specificity of the test, driver mutations in epidermal growth factor receptor L858R and L861Q were analyzed. Clinical specificity was established by comparison with healthy volunteers. Regular monitoring was established during treatment with tyrosine kinase inhibitors. The overall survival of patients was correlated with changes in circulating tumor DNA (ctDNA). Results: Baseline clinical correlation of urinary ctDNA and matched tumor specimens achieved 89% concordance. The clinical specificity was 100%. The average background level of urinary ctDNA was 20.7 ng/mL. Comparing patients with and without bone metastasis, the latter had significantly lower baseline levels. During treatment, more pronounced decline in urinary ctDNA was observed in patients without bone metastasis. In our Kaplan–Meier estimator, we observed that patients with a more significant reduction in ctDNA had a better overall survival outcome. Conclusion: Our study demonstrates clear benefits and allows better risk profiling for NSCLC patients with bone metastasis. The non-invasive specimen collection is attractive and complements existing cancer management tools.