Urologists and their patients may soon be able to determine renal cell tumor histology without surgery or biopsy.
San Francisco-Urologists and their patients may soon be able to determine renal cell tumor histology without surgery or biopsy. A new antibody contrast agent used in conjunction with positron emission tomography-computed tomography shows, in preliminary analyses, preoperative sensitivity of about 86% and specificity of about 87% for clear cell renal cell carcinoma. The contrast agent, girentuximab (Redectane), is being submitted for marketing approval by FDA.
The need for a presurgical diagnostic for clear cell RCC has been recognized for some time, Dr. Divgi said during a presentation at the 2010 Genitourinary Cancers Symposium in San Francisco. PET using fluorodeoxyglucose, or FDG-PET, has become an established component of cancer imaging in many tumors. But it is not useful for imaging clear cell RCC because renal excretion effectively precludes imaging and detection of primary renal tumors. That leaves conventional CT as the diagnostic standard of care, which is considered to be a less than optimal modality for RCC because it cannot distinguish between different tumor histologies.
Investigation into the basic biology of RCC has identified multiple pathways that have been targeted by a growing list of agents, including bevacizumab (Avastin), sunitinib (Sutent), sorafenib (Nexavar), erlotinib (Tarceva), gefitinib (Iressa), temsirolimus (Torisel), and everolimus (Afinitor). Investigators have also identified carbonic anhydrase-IX (CAIX) as a marker that is highly specific for clear cell RCC. CAIX is upregulated in more than 95% of clear cell RCC but is rarely expressed in indolent RCC and is not expressed by benign tumors, including angiomyolipoma and oncocytoma.
Researchers developed a chimeric murine antibody to CAIX, based on the hypothesis that such an antibody would provide a reliable preoperative clear cell diagnosis that could guide surgical planning and subsequent management in patients with renal masses. The antibody was designed to be used as a contrast agent with PET-CT. A proof of concept study showed 94% sensitivity and 100% specificity for clear cell RCC in 26 patients with renal tumors scheduled for nephrectomy. The results give a positive predictive value of 100% and a negative predictive value of 90%.
Promising preliminary phase III data
A pivotal phase III study, REDECT, was developed with input from FDA in the form of a special protocol assessment, Dr. Divgi said. The 14-site study enrolled 266 patients between May 2008 and September 2009, with the final patient visit on Nov. 25, 2009. Results from girentuximab were compared with standard PET-CT scans as well as pathologic reports from all of the tumors.
Detailed data from the trial have not been released, but Dr. Divgi revealed preliminary sensitivity (86%) and specificity (87%) results as well as an outline of adverse event results. There were approximately 870 adverse events recorded in the trial, 93% of which were unrelated to girentuximab. There were 44 significant adverse events reported, most of them postoperative complications.
"We are reasonably sure that girentuximab works as a noninvasive presurgical diagnostic to determine the RCC type in patients with renal masses," he concluded. "The agent is safe and effective for the presurgical identification of clear cell renal cell carcinoma."
Dr. Divgi has disclosed that he is a consultant/adviser for Wilex.
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