by Denise Heady, University of California, Los Angeles

Representative imaging with [⁸⁹Zr]Zr-girentuximab. Credit: The Lancet Oncology (2024). DOI: 10.1016/S1470-2045(24)00402-9

A new study led by investigators from the UCLA Health Jonsson Comprehensive Cancer Center has demonstrated a new, non-invasive imaging technique can accurately detect clear-cell renal cell carcinoma, the most common form of kidney cancer.

The findings, published in The Lancet Oncology, could greatly reduce the number of unnecessary surgeries and ensure that patients receive the right treatment at the right time, potentially changing how doctors diagnose and treat the disease in the future.

"If kidney cancer is diagnosed late, the chances of survival drop significantly, especially if the cancer has spread," said Dr. Brian Shuch, director of the Kidney Cancer Program and the Alvin & Carrie Meinhardt Endowed Chair in Kidney Cancer Research at UCLA, and lead author of the study.

"But if caught early, over 90% of patients can survive for at least five years. If we are going to survey more tumors, it's crucial to accurately identify clear-cell renal cell carcinoma early on as they have a greater propensity to grow and spread."

Kidney cancers, known as renal cell carcinomas, make up 90% of solid kidney tumors. Every year more than 81,000 people in the United States are diagnosed with kidney cancer. Among the many types of these cancers, the most common and deadly is clear-cell renal cell carcinoma, which accounts for 75% of cases and 90% of kidney cancer deaths. Traditional imaging methods like CT or MRI often struggle to differentiate between benign and malignant tumors, leading to either unnecessary surgeries or delayed treatment.

To help improve the detection of clear-cell renal cell carcinoma, the team tested a non-invasive method that uses a monoclonal antibody drug called 89Zr-TLX250, which targets the protein CA9 that is often found in clear-cell renal cell carcinoma.

The phase 3 trial, called ZIRCON, included 332 patients with suspect lesions detected on their kidney from 36 research hospitals from nine different countries with UCLA leading international accrual. The average age of participants was 61 years, with 71% being male and 29% female.

The patients were injected with 89Zr-TLX250, which travels through the body and attaches to the protein CA9 if present in the kidney mass. CA9 is highly expressed in up to 95% of clear cell kidney cancers with minimal expression in normal tissue.

A few days after the injection, patients received a PET-CT scan to detect the radioactive part of the drug, which lights up on the scan wherever the protein is present, allowing doctors to see the cancer more clearly. By looking at the scan, doctors can determine if the kidney mass is likely to be cancerous based on whether or not the 89Zr-TLX250 has attached to the cancer cells.

The new imaging method accurately identified the presence of cancer in most cases while minimizing false positives, demonstrating a high performance with 85.5% sensitivity and 87.0% specificity.

The technique also proved effective even in very small renal masses (less than 2 cm), which are increasingly detected due to more frequent use of abdominal imaging. Additionally, the procedure was shown to be safe, with no significant side effects associated with the use of 89Zr-TLX250.

"The implications of this research are vast," said Shuch. "If adopted widely, 89Zr-TLX250 PET-CT imaging could become a new standard in kidney cancer diagnostics, like how PET-CT imaging has revolutionized prostate cancer management. It could also aid in the detection of other types of kidney cancers and help monitor patients at high risk of metastasis."

"Since joining the UCLA Kidney Cancer Program in the late 1990s with UCLA's Dr. Arie Belldegrun, a main research focus has been on the CA9 protein, a key marker in kidney cancer," said study co-author Dr. Allan Pantuck, professor of urology and vice chair of academic affairs for UCLA Urology. "Over the years, our group has explored its potential as a diagnostic and prognostic biomarker, a therapeutic target and a tool for molecular imaging.

"Our work has led to significant advancements, including clinical trials involving the antibody girentuximab and a UCLA-initiated dendritic cell immunotherapy led by Dr. Alexandra Drakaki, an associate professor of medicine and urology at UCLA. It is very gratifying to see how our pioneering research has contributed to the success of the 89Zr-TLX250 clinical trial, which we believe will help reduce unnecessary surgeries and improve treatment outcomes for patients."

The team will now be looking to see whether 89Zr-TLX250 PET-CT imaging can also identify disseminated or distant disease. A new clinical trial (CANINE) is underway with the aim of detecting metastasis earlier in high-risk patients after nephrectomy. This could help determine proper treatment after surgery. Accurate imaging could intensify planned adjuvant therapy if disease is present or potentially spare patients from unnecessary treatment if disease is absent.

More information: Brian Shuch et al, [89Zr]Zr-girentuximab for PET–CT imaging of clear-cell renal cell carcinoma: a prospective, open-label, multicentre, phase 3 trial, The Lancet Oncology (2024). DOI: 10.1016/S1470-2045(24)00402-9

Journal information: Lancet Oncology 

Provided by University of California, Los Angeles