SUO 2019: On-treatment Circulating Tumor Cell Subtypes and Baseline T-cell Population Are Biomarkers for Response to Immunotherapy and Survival in Metastatic Genitourinary Cancer Patients

Washington, DC ( The analysis of circulating tumor cells (CTC) is a promising new method for gaining insight into the tumor biology in individual patients. Like traditional biomarkers, CTC analysis is non-invasive – requiring only a peripheral blood draw – so it can be performed repeatedly throughout a patient’s disease course.  However, since actual malignant cells are being isolated and examined, the amount of information that can be obtained through CTC analysis theoretically approaches that which could be obtained from direct sampling of the tumor tissue, leading to the popular description of CTC analysis as a “liquid biopsy”. Finally, counting and analyzing the tumor cells found in circulation may even lend more useful insights than sampling of static tumor in the primary mass or metastatic site.

In this presentation during the oral abstract session of the 2019 Society for Urologic Oncology annual meeting, Dr. Heather Chalfin described her work investigating the correlation between CTCs and outcomes of treatment of metastatic genitourinary cancers with immunotherapy.

Her group used the EpicCTC platform to analyze samples from patients with metastatic genitonurinary tumors who were being treated with either cabozantinib/nivolumab or cabozantinib/nivolumab/ipilimumab. With this method, nucleated cells are isolated and stained with a combination of antibodies. In this case pan-CK/CD45/PD-L1/DAPI was used to identify CTCs and CD4/CD8/Ki-67/DAPI was used to identify T-Cells. The EpicCTC platform then visually analyzes the cells, identifying their cell type by the staining patterns and taking other measurements of their morphology.

The study population consisted of 61 patients, 39 with metastatic urothelial carcinoma of the bladder, 4 with clear cell renal carcinomas, and the remaining with rare GU malignancies (e.g. 8 with adenocarcinoma of the bladder 2 with small cell carcinoma of the bladder, 2 patients with penile cancer, and 2 with renal medullary carcinoma). CTC burden was quantified prior to treatment and at cycle 2 and cycle 3.

CTCs were identified in 70% of patients at baseline and at cycle 2 of treatment. CTC burden of >1cell/mL at cycle 2 was associated with significantly worse overall survival. Cluster analysis of CTC staining and morphology identified two subtypes of CTCs which were associated with significantly worse overall survival when found in concentrations >1cell/mL at this same time point. One subtype was characterized by medium CK intensity, high circularity, and low specking and the other was characterized by large cell volume, speckled cytokeratin, and numerous nucleoli. Low CD4 and CD8 T cell counts at baseline were also found to be associated with worse prognosis.

There is much work left to be done before this analysis can be applied clinically, however the ability to correlate CTC data with clinical outcomes at this early stage raises many hopes for the future of this technology.

Presented by: Heather Chalfin, James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, Maryland

Written by: Marshall Strother, MD, Society for Urologic Oncology Fellow, Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia PA, @mcstroth, at the 2019 Society for Urologic Oncology Annual Meeting – December 4-6, 2019 – Washington, DC

1. Werner SL, Graf RP, Landers M, et al. Analytical Validation and Capabilities of the Epic CTC Platform: Enrichment-Free Circulating Tumour Cell Detection and Characterization. J Circ Biomark. 2015;4:3.