This study investigates the role of circulating and urinary exosomal microRNAs (miRNAs) as potential biomarkers for predicting response to systemic therapy in patients with advanced renal cell carcinoma. Patients receiving immune checkpoint inhibitors or targeted therapies are followed during the first 16 weeks of treatment. Blood and urine samples are collected at predefined time points for analysis of exosome-associated miRNAs. Imaging assessments are performed as part of routine clinical follow-up. The aim of the study is to identify exosomal miRNA profiles associated with treatment response and to support the development of non-invasive predictive biomarkers in advanced kidney cancer.

Advanced renal cell carcinoma is commonly treated with immune checkpoint inhibitors and targeted therapies; however, patient response is heterogeneous and reliable predictive biomarkers are limited. Exosomes are extracellular vesicles released by cells into body fluids and contain molecular cargo such as microRNAs (miRNAs), which may reflect tumor biology and immune response. Circulating and urinary exosomal miRNAs represent promising non-invasive biomarkers that could support early prediction of treatment response.

This prospective clinical study evaluates changes in the expression of selected exosome-associated miRNAs in blood and urine and their association with response to systemic therapy in patients with advanced renal cell carcinoma. Eligible participants include patients treated in the first- or second-line setting with immune checkpoint inhibitors or targeted agents. Participants provide blood samples (approximately 10 mL) at four predefined time points and urine samples (approximately 50 mL) at two predefined time points during the first 16 weeks of therapy. Samples are processed according to a standardized protocol including centrifugation and storage at low temperature until further analysis.

Laboratory procedures include isolation of extracellular vesicles from plasma and urine, quantification of extracellular vesicles using nanoparticle tracking analysis, and isolation of exosome-associated miRNA followed by quantitative PCR (qPCR) for selected target miRNAs. Quality assessment of samples is performed, including evaluation of hemolysis and additional purity controls.

Clinical data and radiological imaging results collected during routine clinical management are used to assess treatment response. The primary objective is to identify associations between exosomal miRNA expression patterns and treatment response during early therapy. The study aims to contribute to the development of minimally invasive biomarkers for prediction of therapy response in advanced kidney cancer and to improve patient stratification for systemic treatment.

Inclusion Criteria:

• Adults (≥18 years)
• Histologically confirmed advanced or metastatic renal cell carcinoma
• Receiving systemic treatment with immune checkpoint inhibitors and/or targeted therapy (first- or second-line therapy)
• Ability to provide blood and urine samples according to the study protocol
• Written informed consent

Exclusion Criteria:

• Age <18 years
• Inability to provide required blood and urine samples
• Inability to provide informed consent
• Any condition preventing participation according to investigator assessment