Small renal masses (SRM), especially those under 7 cm pose significant diagnostic challenges when using conventional imaging (CT/MRI). PET/CT with [89Zr]Zr-girentuximab offers a promising alternative in this setting by enabling molecular-level imaging. The ZIRCON trial, a phase 3 multicenter study, evaluated the diagnostic accuracy of [89Zr]Zr-girentuximab PET/CT in detecting clear cell renal cell carcinoma (ccRCC) in SRM. A total of 300 patients with indeterminate renal masses received a single intravenous dose of [89Zr]Zr-girentuximab, followed by PET/CT imaging 5 days post-injection. Generally, sensitivity and specificity for ccRCC detection were 85.5% and 87.0%, respectively. However, smaller masses (maximum diameter: ≤4 cm) demonstrated strong diagnostic performance, with mean sensitivity and specificity of 85% and 89.5%, respectively. PET positivity was observed exclusively in malignant lesions. Nevertheless, both benign and malignant non-ccRCC tumors are 'cold' at [89Zr]Zr-girentuximab, thus differential diagnosis remains an unresolved issue. Despite its strengths, the trial highlights limitations: restricted imaging scope to the abdomen, lack of a cost-effectiveness analysis, concerns over radiation exposure given zirconium-89's 78.4-hour half-life, and the daily scheduling of the examination. Only further studies and time will reveal whether the ZIRCON trial's findings will shine like a diamond or remain akin to zircon - brilliant but constrained in value.
Expert review of anticancer therapy. 2025 Jan 15 [Epub ahead of print]
Luca Filippi, Luca Urso, Rolando Maria D'Angelillo, Laura Evangelista
Nuclear Medicine, Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy., Department of Translational Medicine, University of Ferrara, Ferrara, Italy., Radiation Oncology, Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy., Department of Biomedical Science, Humanitas University, Pieve Emanuele, Milan, Italy.