Girentuximab imaging in renal cancer: diamond in the rough or just ZIRCON?

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-h 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.