# Clinical, Genomic, and Transcriptomic Characteristics of Patients with Metastatic Renal Cell Carcinoma Who Developed Thromboembolic Events

## TL;DR

This study explores why some patients with advanced kidney cancer develop blood clots and identifies possible genetic factors linked to this complication.

## Contribution

The study identifies genomic and transcriptomic patterns associated with thromboembolic events in metastatic renal cell carcinoma patients.

## Key findings

- Thromboembolic events occurred in 11% of metastatic renal cell carcinoma patients.
- Xenobiotic metabolism and mTORC1 signaling pathways were most upregulated in patients with thromboembolic events.
- Patients with favorable risk profiles were less likely to develop thromboembolic events.

## Abstract

Thromboembolic events (TE) are a common complication in patients with metastatic renal cell carcinoma (mRCC) and are associated with poorer clinical outcomes. However, the incidence of TE and clinical and genomic characteristics of patients with mRCC who develop this complication are poorly understood. Herein, we describe the incidence and clinical features of patients with mRCC with or without TE at our institution, and examine their association with the underlying genomic and transcriptomic characteristics of the tumor. This retrospective study included all consecutive cases of mRCC seen at our institution. A CLIA-certified lab performed tumor genomics and transcriptomics. Patients were classified based on the presence of a TE within the first year of diagnosis. Three hundred and seventy patients with mRCC were included in the study. TE was seen in 11% (42) of the patients. Patients with favorable International mRCC Database Consortium (IMDC) risk were less likely to develop a TE. In contrast, patients receiving combination treatment with a tyrosine kinase inhibitor (TKI) and an immune checkpoint inhibitor were more likely to develop a TE. No difference in overall survival among patients with or without TE was observed (52 vs. 55 months; HR 0.85, 95% CI 0.5574–1.293, p = 0.24). The most upregulated pathways in mRCC with TEs versus those without were the xenobiotic metabolism and mTORC1 signaling pathways. Our findings suggest potential biomarkers that, after external validation, could be used to better select patients who would benefit from prophylactic anticoagulation.