Urologists may soon have an imaging tool that lets them distinguish between aggressive clear cell renal cell carcinoma (RCC) and less aggressive or benign renal masses, researchers said here at the 2010 American Urological Association (AUA) Annual Meeting.
Final data on a study of radio-labelled 124I-girentuximab shows that the antibody suggests that clinicians can use the agent to enhance positron emission tomography (PET)/computed tomography (CT) scans to selectively identify aggressive tumours that are appropriate for immediate surgery.
A noninvasive scan that could offer a differential diagnosis between clear cell RCC and nonmalignant kidney masses could reduce the rate and incidence of unnecessary renal surgery with the associated morbidity, mortality, and economic burden.
Robert Uzzo, MD, Fox Chase Cancer Center, Philadelphia, Pennsylvania, unveiled final data from the phase 3 REDECT trial of 124I-girentuximab as a late-breaking abstract here on June 3. The 14-centre study was conducted under a Special Protocol Assessment (SPA) from the Food and Drug Administration.
Clear cell RCC is a particularly aggressive phenotype of RCC and accounts for up to 75% of renal cell tumours discovered incident to other imaging procedures, Dr. Uzzo noted. Clear cell RCC cells also express carbonic anhydrase-IX (CAIX), a protein that is only rarely expressed by non-clear cell variants and is not expressed in benign tumours such as oncocytoma or angiomyolipoma. Girentuximab binds selectively to CAIX, which makes the radio-labelled form of the agent a highly specific marker for clear cell RCC.
Before the development of this selective marker, only histopathologic examination could distinguish clear cell RCC from an indolent malignancy or a nonmalignant mass. Dr. Uzzo suggested that the agent could change current treatment paradigms that encourage surgery for most renal masses.
A pilot study at Memorial Sloan Kettering Cancer Center, New York, New York, in 2005-2006 showed that 124I-girentuximab could identify clear cell RCC with 94% sensitivity and 100% specificity in 26 patients. A phase 3 was launched at 14 US centres to confirm the findings.
Researchers gave 124I-girentuximab to 204 patients with primary renal masses confirmed by diagnostic CT scan who were already scheduled for resection. The drug was administered by a 15-minute infusion and given a PET/CT scan 2 to 6 days later and before surgery. All of the patients had state-of-the-art multiphasic diagnostic CT of the abdomen immediately following the PET/CT. The PET/CT and diagnostic CT scans were assessed by a blinded panel of 3 central readers for each group. Following resection, tumour specimens were evaluated by a central pathologist who was blinded to both local pathology results and to imaging results.
Of the original 204 patients who were infused and imaged, 202 underwent surgery and 197 had evaluable PET/CT and diagnostic CT as well as renal tumour specimens for histopathologic evaluation. Within the surgical group, 146 patients had clear cell RCC and 56 had other tumour histologies. The radio-labelled antibody showed high sensitivity for clear cell RCC (86%), high specificity (87%), and high accuracy (86%), Dr. Uzzo reported. The positive predictive value was 95% and the negative predictive value was 70%.
Dr. Uzzo added that PET/CT scans using the agent also identified metastases that are typically unseen by diagnostic CT. Memorial Sloan Kettering plans to study the agent in monitoring clear cell RCC therapy and to detect metastases. Sequential scans could provide valuable information on disease progression and the need to switch to alternative treatment regimens.