A recent study has revealed an innovative, non-invasive imaging technique that can effectively identify clear-cell renal cell carcinoma, which is the most prevalent type of kidney cancer.
Research from the UCLA Health Jonsson Comprehensive Cancer Center has uncovered a groundbreaking, non-invasive imaging method capable of accurately detecting clear-cell renal cell carcinoma, the most common kidney cancer.
These findings, which appear in The Lancet Oncology, have the potential to significantly decrease unnecessary surgeries and ensure patients receive appropriate treatment timely, possibly transforming how medical professionals diagnose and manage the condition in the future.
“Late diagnosis of kidney cancer drastically lowers survival chances, especially if the disease has progressed,” explained Dr. Brian Shuch, who directs the Kidney Cancer Program and holds the Alvin & Carrie Meinhardt Endowed Chair in Kidney Cancer Research at UCLA and is the principal author of the study. “However, if detected in its early stages, over 90% of patients can survive for a minimum of five years. Therefore, accurately identifying clear-cell renal cell carcinoma early is vital, as these tumors tend to grow and spread more aggressively.”
Renal cell carcinomas comprise 90% of solid kidney tumors. Every year, more than 81,000 individuals in the U.S. receive a kidney cancer diagnosis. Of the various kidney cancer types, clear-cell renal cell carcinoma is the most common and lethal, accounting for 75% of cases and 90% of kidney cancer fatalities. Standard imaging techniques like CT scans or MRIs often have difficulty distinguishing between benign and cancerous tumors, which can lead to unnecessary surgeries or treatment delays.
To enhance the identification of clear-cell renal cell carcinoma, the research team investigated a non-invasive approach using a monoclonal antibody drug known as 89Zr-TLX250. This drug targets the CA9 protein, frequently present in clear-cell renal cell carcinoma.
The phase 3 trial, referred to as ZIRCON, involved 332 patients with suspicious kidney lesions from 36 research institutions across nine countries, with UCLA spearheading the international participant collection. The participants averaged 61 years of age, with 71% male and 29% female.
The study subjects received an injection of 89Zr-TLX250, which circulates throughout the body and binds to the CA9 protein when found in the kidney mass. This protein is highly expressed in nearly 95% of clear-cell kidney cancers, with minimal presence in normal tissues.
A few days post-injection, patients underwent a PET-CT scan to detect the radioactive portion of the drug, which illuminates on the scan wherever the protein is present, providing a clearer view of the cancer. Doctors can then assess whether the kidney mass is likely malignant based on the attachment of 89Zr-TLX250 to the cancer cells.
This new imaging method successfully identified cancer presence in most instances while reducing false positives, showcasing strong results with 85.5% sensitivity and 87.0% specificity.
The technique was also effective for very small renal masses (less than 2 cm), which are now more frequently identified due to increased abdominal imaging. Furthermore, the procedure was confirmed to be safe, with no major side effects linked to the use of 89Zr-TLX250.
“The possibilities stemming from this research are immense,” stated Shuch. “If widely implemented, 89Zr-TLX250 PET-CT imaging could establish a new standard for kidney cancer diagnosis, similar to how PET-CT imaging has transformed prostate cancer treatment. It may also assist in identifying other kidney cancer types and aid in monitoring patients at heightened risk of metastasis.”
“Since collaborating with UCLA’s Dr. Arie Belldegrun in the late 1990s, a primary research focus has been the CA9 protein, a crucial marker in kidney cancer,” mentioned study co-author Dr. Allan Pantuck, a professor of urology and vice chair of academic affairs for UCLA Urology. “Our team has investigated its potential as a diagnostic and prognostic biomarker, a therapeutic target, and a method for molecular imaging. Our efforts have led to significant progress, including clinical trials for the antibody girentuximab and a UCLA-initiated dendritic cell immunotherapy directed by Dr. Alexandra Drakaki, an associate professor of medicine and urology at UCLA. It is fulfilling to see how our pioneering research has advanced the success of the 89Zr-TLX250 clinical trial, which we believe will help decrease unnecessary surgeries and enhance treatment outcomes for patients.”
The research team is now exploring whether 89Zr-TLX250 PET-CT imaging can also detect disseminated or distant disease. A new clinical trial (CANINE) is being conducted with the goal of identifying metastasis in high-risk patients sooner following nephrectomy. This could refine post-surgery treatment decisions. Accurate imaging might intensify planned adjuvant therapies if disease is detected and perhaps spare patients from undue treatment if no disease is present.
The study received sponsorship from Telix Pharmaceuticals.
