AI-Powered Kidney Cancer Detection

Researchers from the UCLA Health Jonsson Comprehensive Cancer Center have demonstrated in a recent study that their novel non-invasive imaging method can reliably detect clear-cell renal cell carcinoma, the most common form of kidney cancer. The study was published in The Lancet Oncology.

The findings could significantly reduce unnecessary surgeries and ensure that patients receive the appropriate care at the right time, potentially transforming future diagnosis and treatment of the condition.

If kidney cancer is diagnosed late, the chances of survival drop significantly, especially if the cancer has spread. 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.

Dr. Brian Shuch, Study Lead Author and Director, Kidney Cancer Program, University of California Los Angeles

90 % of solid kidney tumors are kidney cancers, also known as renal cell carcinomas, which affect over 81,000 people annually in the United States. Clear-cell renal cell carcinoma is the most common and deadliest form, accounting for 75 % of cases and 90 % of kidney cancer deaths.

Conventional imaging techniques like CT or MRI often struggle to differentiate between benign and malignant tumors, leading to delays in treatment or unnecessary surgeries.

To improve detection, the team tested a non-invasive method targeting the protein CA9, which is commonly present in clear-cell renal cell carcinoma. They used a monoclonal antibody drug called ⁸⁹Zr-TLX250, which binds to CA9 if found in kidney masses.

In the phase 3 ZIRCON trial, 332 patients with suspected kidney lesions from 36 hospitals across nine countries were enrolled, with UCLA leading international recruitment. The average age of participants was 61, and 71 % were male. The injected ⁸⁹Zr-TLX250 traveled through the body and attached to the CA9 protein, which is minimally present in healthy tissue but highly expressed in up to 95 % of clear-cell kidney cancers.

A few days after the injection, patients underwent a PET-CT scan to detect the radioactive component of the drug, which lights up the scan where the CA9 protein is present. This provided a clearer view of the cancer, enabling doctors to determine whether the kidney mass is likely malignant based on the binding of ⁸⁹Zr-TLX250 to cancer cells.

The imaging method demonstrated strong results, with 85.5 % sensitivity and 87.0 % specificity, correctly identifying cancer in most cases while reducing false positives. It was also effective in detecting very small renal masses (under 2 cm), a growing issue with the increased use of abdominal imaging. Additionally, the procedure proved safe, with no significant side effects from the ⁸⁹Zr-TLX250.

Shuch added, “The implications of this research are vast. 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.”

Study Co-Author Dr. Allan Pantuck, Professor of Urology and Vice Chair of Academic Affairs for UCLA Urology, stated, “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. 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.”

Dr. Pantuck further added, “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’s next goal is to determine whether ⁸⁹Zr-TLX250 PET-CT imaging can also detect distant or disseminated disease. A new clinical trial called CANINE is underway to determine if this imaging method can identify metastases in high-risk patients after nephrectomy. This could help inform decisions on post-surgery treatment.

Accurate imaging could enhance adjuvant therapy if disease is detected or spare patients from unnecessary treatments if no disease is found.

The study was sponsored by Telix Pharmaceuticals.

Journal Reference:

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