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Dr. Brian Shuch

A new way to scan and image renal masses has the potential to accurately determine if a renal mass is cancerous or benign before a patient needs to have surgery.

The phase 3 ZIRCON trial successfully demonstrated both sensitivity and specificity – the two primary endpoints – for clear cell renal cell carcinoma (ccRCC) using the zirconium-tagged antibody girentuximab (89Zr-DFO-girentuximab), which binds to a molecule that is common on the the surface of many ccRCC cells but is not common on normal tissues. This tag is visible via positron emission tomography and computed tomography (PET CT) scans.

“I don’t know about you but I’m tired of removing benign tumors and 20-30% of the tumors we remove that are small are ultimately benign,” said Dr. Brian Shuch, Director of the Kidney Cancer Program at the University of California, Los Angeles Institute of Urologic Oncology, who presented the ZIRCON results at the recent American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU).

“Having an accurate non-invasive method that helps pre-treatment risk stratification would really change the field.”

“A renal mass biopsy, while it’s generally safe, it’s invasive, it’s performed infrequently, and it’s often non diagnostic at many centers. Having an accurate non-invasive method that helps pre-treatment risk stratification would really change the field.”

Knowing whether an indeterminate mass is cancerous or not is an is an unmet need in kidney cancer, particularly among people with small masses. For indeterminate masses, the risks of invasive surgery to remove all or part of the kidney and/or to biopsy could be greater than a different course of treatment or active surveillance.

The trial included 371 patients with early-stage disease, median age 62 and median mass size of 3.7 cm, who were scheduled for partial nephrectomy within 90 days of dosing with the girentuximab trial agent. While 2/3 of the tumors were determined to be ccRCC in the study cohort, based on surgical samples, the rest were other less common lesion types including papillary RCC, chromophobe RCC, oncocytoma, and other types still being evaluated. About 1/8 of the cohort had kidney lesions of 2 cm or less.

Reviews of the PET CT scans 3-7 days after dosing with the girentuximab agent showed, on average, the sensitivity was 86% and specificity was 87% for predicting the presence of ccRCC – the co-primary endpoints – and this was confirmed with pathology after surgery. The trial was similarly successful at meeting the two secondary endpoints, with 85% sensitivity and 89% specificity in detecting ccRCC in smaller tumors 4 cm or less. The results showed useful positive and negative predictive value for detecting ccRCC, at 93% and over 75%, respectively, for both the primary and secondary endpoints. Adverse events were mostly mild and mostly related to surgery, Shuch said, including wound infections and hernias.

For the trial to be considered positive, Shuch said, the endpoints had to exceed the benchmark floor set by the FDA of 70% sensitivity and 68% specificity for identifying ccRCC, which they did.

“I see this as patients getting a scan up front and then the positive ones are good candidates to get treated. The zircon-negative ones… maybe those that are the ones you’re going to biopsy,” Shuch said, speaking on the Uromigos podcast.

“This is like a new way of imaging clear cell kidney cancer that could really help plan for surgery, whether or not lymph nodes are involved, or how far you have to resect, or do you need to resect,” said Dr. Daniel George, medical oncologist at the Duke Cancer Institute and Chair of the Kidney Cancer Association’s Medical Steering Committee, who was not involved in the trial.

“It could also help us potentially follow metastatic disease in patients who are undergoing treatment – is the cancer responding and is a residual tumor still active, does it have cancer or not. I think this could be a really important aspect to how we follow patients, how we identify patients, and treat patients with localized and advanced kidney cancer.”

The girentuximab agent is not yet approved or available for use commercially, but Shuch said this ‘molecular biopsy’ has the potential to improve care by improving the identification of ccRCC compared to any other conventional cross-sectional imaging.

Dr. Brian Shuch spoke previously with the KCA about exciting advancements in kidney cancer, including imaging technology that would allow doctors to visualize cancerous kidney masses before the need for invasive surgeries.

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