A recent phase III trial has indicated that zirconium Zr-89–labeled girentuximab (Zr-89 girentuximab) positron-emission tomography/computed tomography (PET-CT) imaging is highly accurate in detecting clear cell renal cell carcinoma (RCC) in patients presenting with renal masses. The study, published in The Lancet Oncology, highlights the potential of this imaging modality to improve the characterization of renal masses and guide clinical decision-making.
The trial enrolled 300 patients with indeterminate renal masses (up to 7 cm) suspicious for clear cell RCC across multiple sites in nine countries. Participants received a single dose of Zr-89 girentuximab (37 MBq ± 10%; 10 mg of girentuximab), followed by abdominal PET-CT 5 days (± 2 days) later. Nephrectomy was performed no later than 90 days after administration of Zr-89 girentuximab. The primary analysis included 284 patients (95%) with evaluable PET-CT findings and confirmed histopathologic diagnoses made by three independent readers.
Accuracy and Predictive Value
The results showed that Zr-89 girentuximab PET-CT had a mean sensitivity of 85.5% (95% CI = 81.5%–89.6%) and a mean specificity of 87.0% (95% CI = 81.0%–93.1%) for clear cell RCC. The mean positive predictive value was 92.9% (95% CI = 90.2%–95.7%), the mean negative predictive value was 75.2% (95% CI = 71.2%–79.3%), and the mean accuracy was 86.0% (95% CI = 85.0%–87.0%). These findings suggest a high level of diagnostic accuracy for this imaging technique.
Safety Profile
The safety profile of Zr-89 girentuximab was found to be favorable. Most adverse events were considered unlikely to be related or not related to Zr-89 girentuximab, with 193 of 261 adverse events of any grade (74%) occurring during or after surgery. The most common grade ≥ 3 adverse events were postprocedural hemorrhage (2%), urinary retention (1%), and hypertension (1%). A total of 52 serious adverse events occurred in 25 patients (8%), with 51 (98%) occurring after surgery. Thirteen adverse events in eight patients (3%) were considered possibly or definitely related to Zr-89 girentuximab, including diarrhea, abdominal pain, fatigue, asthenia, pyrexia, hypoesthesia, back pain, urinary retention, dysuria, night sweats, and increased urine output. No treatment-related deaths were reported.
Clinical Implications
The study's investigators, led by Brian Shuch, MD, of the Institute for Urologic Oncology, University of California Los Angeles, concluded that Zr-89 girentuximab PET-CT has a favorable safety profile and is a highly accurate, noninvasive imaging modality for the detection and characterisation of clear cell renal cell carcinoma. Zr-89 girentuximab has high affinity for carbonic anhydrase 9, a tumor antigen highly expressed in clear cell RCC, which contributes to its effectiveness. According to Dr. Shuch, this imaging technique has the potential to be practice-changing, offering a more precise method for identifying and characterizing clear cell RCC, ultimately improving patient outcomes.
The study was funded by Telix Pharmaceuticals. Full disclosures of the study authors are available at thelancet.com.
