Diagnosis and monitoring of recurrent clear cell renal cell arcinoma with Girentuximab

The diagnosis of kidney cancer is a diagnostic dilemma: currently up to 50% of renal cell carcinoma (RCC) is detected incidentally as a small renal mass (SRM). About 20-25% of SRMs concerns a non-malignant process and active surveillance may be a safe alternative to surgical management, particularly in fragile patients. In addition, non-invasive confirmation of the presence or absence of RCC can be useful to guide clinical decision making in patients suspected of recurrent or metastatic RCC. The Radboudumc was one of the first clinical institutes in the world studying targeting of Carbonic Anhydrase 9 (CA9) as early as 1997 and is now internationally recognized for the diagnostic and therapeutic efforts in patients with clear cell RCC (ccRCC). CA9 is specifically upregulated in ccRCC due to mutations that initiate the disease (Oncogene 2004), and it is therefore almost ubiquitously expressed in ccRCC, making it a good targeting molecule (Eur Urol 2010). CA9 targeting was achieved with the monoclonal antibody Girentuximab (also called cG250, Int J Cancer 1986). Initially, patients with primary renal masses were imaged by planar imaging (J Clin Oncol 1997; Cancer Res 1999) , followed by studies with single-photon emission computed tomography (SPECT, Eur Urol 2013). These studies unambiguously showed that Girentuximab could specifically detect primary and metastatic ccRCC. Studies with non-labeled Girentuximab have suggested that this may alter the disease course in metastatic RCC patients (Br J Cancer 2004). In close collaboration with the departments of Urology and Nuclear Medicine leaders from the Urological cancers theme of the Radboudumc have published pivotal studies validating the ability of Girentuximab to distinguish non-ccRCC from ccRCC (Eur Urol 2013), to aid in therapy monitoring or for use as additional therapy (Eur Urol 2016) in total more than 50 peer-reviewed manuscripts and 9 thesis defenses). In a recent development positron-emission tomography (PET) imaging for diagnosis (Eur Urol 2018) and fluorescence imaging for surgical support was added (Clin Cancer Res 2016). A large international phase 3 trial will be initiated to establish the clinical value of Girentuximab imaging in patients suspected of primary, recurrent or metastatic ccRCC where conventional diagnostics are inconclusive. In summary, the theme Urological cancers has taken Girentuximab imaging for ccRCC from bench to bedside.