Phase 3 trial of investigational PET–CT imaging in cT1 indeterminate renal masses.

Evidence before this study

We searched PubMed on Oct 16, 2018, for the terms “indeterminate renal mass”, “renal cell carcinoma histology”, and “renal cell carcinoma imaging” with no language or time restrictions. Articles were screened by title and abstract for relevance, and those that explored renal cell carcinoma diagnosis and characterisation, patient management, and consensus guidelines were considered for full-text review. Evidence supports the unmet need for an accurate, non-invasive imaging modality for the detection and characterisation of clear-cell renal cell carcinoma from other renal and extrarenal lesions. The incidence of small renal masses is increasing. Diagnosis and treatment are limited by current imaging techniques, and renal mass biopsy is invasive, often incurs complications such as clinically significant renal haematoma and tumour seeding, and can underestimate tumour grade. Many patients undergo unnecessary surgery to remove masses that are later determined to be benign, and partial nephrectomies can have complications. In a phase 1 trial, [Zr]Zr-girentuximab PET accurately confirmed the presence or absence of metastatic clear-cell renal cell carcinoma and differentiated non-clear-cell renal cell cancers, which favourably impacted decisions for surgery. In line with previous research, this trial also confirmed a favourable safety profile of radiolabelled girentuximab.

Added value of this study

To our knowledge, ZIRCON is the first prospective, open-label, large, multinational, phase 3 trial to assess the diagnostic performance of [Zr]Zr-girentuximab PET–CT to non-invasively detect, differentiate, and characterise clear-cell renal cell carcinoma and other lesions in patients with indeterminate renal masses. Results support the high diagnostic performance and favourable safety profile of [Zr]Zr-girentuximab PET–CT.

Implications of all the available evidence

Delays in the diagnosis of renal cell carcinoma might result in substantially decreased 5-year relative survival rates. Therefore, a high unmet need exists for diagnostic tools that can more accurately classify tumour subtypes, support staging, and help risk stratify patients earlier. [Zr]Zr-girentuximab PET–CT imaging accurately identified clear-cell renal cell carcinoma in patients with a cT1 indeterminate renal mass (≤7 cm), with a favourable safety profile. Given its high diagnostic performance, including for very small lesions, [Zr]Zr-girentuximab PET–CT imaging could support early and accurate diagnosis, inform patient risk stratification and clinical decision making, and reduce overtreatment and undertreatment, thereby leading to improved patient outcomes. Our data support the value of [Zr]Zr-girentuximab PET–CT imaging as a new standard, non-invasive tool for the diagnosis and detection of clear-cell renal cell carcinoma from other renal and extrarenal lesions in clinical practice, minimising the risk of unnecessary invasive interventions. Imaging using [Zr]Zr-girentuximab has the potential to change clinical practice in renal cancer, including staging and monitoring patients at high risk, and detection of distant metastasis. Additional trials to further ascertain effects on patient management and clinical utility of [Zr]Zr-girentuximab PET–CT for other renal cancer subtypes are warranted.

Source: The Lancet Oncology