Background

Despite no evidence of disease by radiological imaging, up to 30% of breast cancer cases are known to relapse after treatment with curative intent. The presence of circulating tumor cells (CTCs) in stage I–II cancer patients signals the activation of extravasation and invasion processes leading to micro-metastasis and may result in poor outcomes. CTCs in blood circulation at any stage of cancer indicate detectable minimal cellular disease (MCD). Thus, the longitudinal investigation of patients with such biomarkers remains highly important for predicting recurrence, therapy escalation, and dose modifications. The expression of programmed death-ligand 1 (PD-L1) on CTCs is a dynamic biomarker, and these cells may escape elimination by the immune system, indicating progression toward a metastatic phenotype.

Methods

Retrospectively, a cohort of 20 cancer patients (including lung, colorectal, breast, stomach, etc.) who had recently undergone treatment were investigated for the presence of CTCs using the CDSCO-approved OncoDiscover platform. The platform contains multi-component systems conjugated with anti-EpCAM antibodies on magnetic nanoparticles. All patients clinically represented stable disease based on previous radiological findings. CTC enumeration was performed using CD45-, EpCAM+, and CK18+ markers, along with the evaluation of PD-L1 overexpression in 1.5 ml of peripheral blood using automated motorized Zeiss fluorescence microscopy.

Results

Despite no radiological evidence of disease and clinically stable status, 75% (n = 15) of the selected patients showed at least one CTC. Among them, 55% (n = 11) had one CTC, 5% (n = 1) had two CTCs, and 15% (n = 3) had three CTCs. In addition, 50% (n = 10) of patients demonstrated PD-L1 expression on CTCs, while one patient exhibited a CTC cluster.

Conclusions

Patients showed circulating residual disease (CRD) despite clinically stable disease, indicating possible progression from localized to secondary disease. Longitudinal monitoring of CTCs with PD-L1 expression may reveal real-time residual disease, progression, regression, and actual response to treatment. CRD monitoring can improve curative outcomes by potentially enhancing progression-free survival (PFS) and overall survival (OS) in solid cancers.