Agent distinguishes clear cell renal cell carcinoma from other masses

"This will likely be the first disease-specific imaging modality for solid tumors," Robert Uzzo, MD, chief of surgery at Fox Chase Cancer Center, Philadelphia, told Urology Times at the AUA annual meeting in San Francisco. "CAT and MRI can distinguish solid from cystic renal lesions but give no information regarding benign versus malignant, histology, or biology of distant disease."

Dr. Uzzo was lead author on the REDECT trial, which compared PET/CT using 124I-girentuximab, or G250 (Redectane), against standard diagnostic CT at 14 centers across the United States. The use of PET/CT with 124I-girentuximab had an 86% sensitivity, 87% specificity, and 95% positive predictive value for clear cell RCC in 202 patients.

During the AUA meeting take-home messages on kidney cancer, Christopher G. Wood, MD, noted that the agent is not yet FDA-approved, "but we are excited about the prospects."

"This could change the way we approach renal masses," said Dr. Wood, associate professor of urology at M.D. Anderson Center, Houston.

Clear cell RCC is a particularly aggressive phenotype of RCC and accounts for up to 75% to 90% of all kidney cancers. More important, clear cell RCC accounts for up to 75% of small renal tumors that are discovered incident to abdominal imaging. These incident discoveries now account for 70% of all new kidney cancer diagnoses.

For now, only histopathologic examination can distinguish clear cell cancers from other renal masses. Because untreated metastatic clear cell RCC is almost 100% fatal, excision remains the standard treatment, even though 25% to 30% of small renal tumors are benign. The combination of PET/CT and 124I-girentuximab could dramatically alter treatment decisions, Dr. Uzzo said. The morbidity associated with biopsy or excision of indolent tumors or benign masses could be greatly reduced by avoiding surgery in those patients.

The antibody binds selectively to carbonic anhydrase-IX (CAIX), a protein that is expressed by more than 95% of clear cell RCC cells. But CAIX is only rarely expressed by non-clear cell RCC variants and is not expressed in benign tumors such as oncocytoma or angiomyolipoma.

FDA submission expected soon

Wilex AG, the manufacturer of the scan, plans to submit it to the FDA later this year, noted Paul Bevan, PhD, the company's director of research and development. The REDECT trial was conducted under an FDA special protocol assessment, which implies the agent could receive a speedy review.

"REDECT shows that this agent takes care of presurgical evaluation of small renal masses," Dr. Bevan said. "We see potential use in evaluating other types of treatment and possibly in other hypoxic tumors."

Possible future trials to come

Assuming the agent is approved for the presurgical identification of clear cell RCC, look for additional trials in the near future. 124I-girentuximab might be used to track the effectiveness of targeted therapy as shown by changes in tumor size and location as well as the effectiveness of ablative therapies. It might also be used to identify metastases.

"If patients are successfully treated by ablation or targeted therapy, the G250 signal should change appropriately," Dr. Uzzo explained. "Moreover, today many clinical decisions are made based on the non-specific enhancement patterns on CT or MR. This technology holds the promise of a biologic endpoint to measure success."