Carbonic anhydrase IX (CAIX) is a cell surface protein expressed in over 90% of clear cell renal cell carcinoma (ccRCC), driven by hypoxia or Von-Hippel Lindau (VHL) loss. The phase 3 ZIRCON trial evaluated 89Zrgirentuximab, a CAIX-targeted positron emission tomography (PET) radiotracer, and met its primary endpoint for the accurate detection of ccRCC in patients with renal masses. Many aggressive forms of non-ccRCC (nccRCC) can express CAIX, which is linked to a hypoxic state. A reanalysis of the trial was performed demonstrating the tracer also identified nccRCC, particularly in forms of papillary RCC (pRCC) with higher CAIX expression (H score) and PET avidity (SUVmax). The positive predictive value for any renal malignancy was 98%, with sensitivity/specificity of 82% and 87%, respectively. This suggests 89Zrgirentuximab has applications beyond the detection of ccRCC in primary renal masses and may have implications to management of nccRCC. PATIENT SUMMARY: The ZIRCON phase 3 trial used an imaging agent (89Zrgirentuximab) with a primary focus to detect the most common kidney cancer, clear cell renal cell carcinoma. Other forms of kidney cancer can express the marker that the imaging agent can identify. The additional analysis showed that when positive, 98% of cases were correctly identified as any form of cancer.
Kaba et al. (Wed,) studied this question.