Systematic Review of Urinary Biomarkers for Detection of Renal Cell Carcinoma

Overview

This systematic review analyzed 46 studies on urinary biomarkers for sporadic renal cell carcinoma (RCC), identifying several promising biomarkers with diagnostic accuracy (AUC ≥ 0.80). Despite promising findings, variability in study quality and biases limit current clinical application.

Background

Renal cell carcinoma (RCC) is the 14th most common cancer worldwide, predominantly affecting older adults with a mean diagnosis age of 75 years. RCC comprises about 90% of kidney cancers, mainly clear cell, papillary, and chromophobe subtypes. Imaging techniques have increased detection of small renal masses, but distinguishing benign from malignant lesions remains challenging, leading to potentially unnecessary nephrectomies. Non-invasive urinary biomarkers could improve early RCC detection and reduce unnecessary surgeries.

Data Highlights

A total of 46 studies published between 2003 and 2025 were included after screening 136 initial articles. Study quality scores ranged from 8.5 to 17.5 on the adapted STROBE checklist (max 20). Selection bias was the most common risk, present in 26.1% of studies, while measurement and reporting biases were less frequent (4.3%). Thirteen studies investigated single biomarkers, and five studied multi-marker panels. Biomarkers with an area under the curve (AUC) ≥ 0.80 were considered promising for clinical utility.

Key Findings

• 46 studies on urinary biomarkers for RCC diagnosis were systematically reviewed, including 4 from a previous DNA methylation biomarker review.
• Study quality varied, with none achieving maximal STROBE scores; selection bias was the most prevalent risk.
• Promising biomarkers were identified based on diagnostic accuracy (AUC ≥ 0.80), though heterogeneity in methods and cut-offs was noted.
• Both single biomarkers and multi-marker panels were evaluated, with some panels showing improved diagnostic performance.
• Despite promising results, no urinary biomarkers have yet been translated into routine clinical practice for RCC detection.

Clinical Implications

Urinary biomarkers hold potential as non-invasive tools to improve early RCC detection and reduce unnecessary nephrectomies for benign lesions. However, standardization of biomarker validation, assay techniques, and cut-off values is essential before clinical implementation. Clinicians should remain aware of current limitations and await further validated biomarkers for routine use.

Conclusion

This review highlights several promising urinary biomarkers for RCC detection but underscores the need for rigorous validation and standardization to enable clinical translation. Future research should focus on overcoming biases and harmonizing methodologies to realize the clinical utility of urinary biomarkers in RCC.

References

1. Global Cancer Observatory (GLOBOCAN) 2022 -- Kidney Cancer Statistics
2. STROBE Statement 2007 -- Guidelines for Reporting Observational Studies
3. PRISMA 2020 -- Systematic Review Reporting Guidelines
4. Previous Systematic Review 2023 -- DNA Methylation Biomarkers for RCC