A research team from Roswell Park Comprehensive Cancer Center has discovered a way to use computed tomography (CT) imaging to assess kidney tumors that test positive for the biomarker CD117 and accurately determine - before surgery - whether the tumor is benign or malignant. The findings have been published in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR).
"A persistent problem in kidney cancer diagnosis has been the inability to reliably determine whether a kidney tumor is cancerous without undergoing surgery to remove the tumor, and sometimes the whole kidney too," says senior author Eric Kauffman, MD, a staff physician and Assistant Professor of Oncology in the Department of Urology at Roswell Park. Surgery for benign kidney tumors is associated with frequent perioperative morbidity and an estimated annual healthcare cost approaching $100 million in the United States alone.
Kidney tumors are one of the few tumor types for which a biopsy cannot always confirm the diagnosis as cancerous or benign, explains Dr. Kauffman. A fine-needle aspiration biopsy doesn't provide enough tissue to make the diagnosis. And while a needle-core biopsy usually can, there's an important exception. When a tumor biopsy tests positive for the biomarker CD117, the diagnosis is narrowed to two potential conclusions: renal oncocytoma, a benign kidney tumor that is not dangerous, and chromophobe renal cell carcinoma (ChRCC), a potentially life-threatening form of kidney cancer.
Biopsies of these two tumor types often look nearly identical under the microscope, sharing characteristic features such as the shape and color of the tumor cells, the appearance of the nuclei and the pattern in which the cells are laid out in the tissue. In addition, they typically share a unique biomarker profile that helps pathologists to differentiate these two tumor types from other kidney tumor types -; but often not from each other.
To be on the safe side, most doctors recommend surgery to remove the tumor or kidney, and may even skip the biopsy since they believe it cannot reliably prove the tumor is benign, Dr. Kauffman explains. In addition, performing needle-core biopsies on the kidney is challenging and requires interventional radiologists with unique training and specialization in this approach. "Roswell Park is fortunate to have interventional radiologists with kidney tumor biopsy expertise, and who are aided by cytopathologists present during the biopsy to ensure biopsy accuracy in real time," he says.
Dr. Kauffman's team of urologists, radiologists and pathologists looked at 124 patients with oncocytoma or ChRCC tumors at Roswell Park. Patients diagnosed from 2003 to 2012 represented a retrospective study group to identify the clinical and radiographic variables associated with the benign condition versus the malignant one, particularly when the signature CD117 biomarker was positive. The team then tested variables prospectively on patients from 2013 to 2017 to validate their findings.
The team found several differentiating factors: larger tumor size and younger patient age were associated with the cancerous tumor type, whereas multiple tumors present simultaneously were associated with the benign condition. However, the most reliable variable was a measurement determined using multiphase contrast CT scanning, which the research team called the tumor-to-cortex Peak Early-phase Enhancement Ratio (PEER).
When a patient receives contrast dye through an IV for a CT scan, it makes the kidney and tumor appear brighter on the scan images. Tumor-to-cortex PEER refers to the level of brightness of the tumor compared to the brightness of the rim (cortex) of the kidney. A CT scan is first done without contrast dye, and then another scan with contrast is taken just as the dye is entering the kidney, referring to "early-phase enhancement," rather than when the contrast leaves the kidney. Essentially, when a CD117-positive tumor appears brighter than the rest of the kidney, it's more likely to be benign, and when it's darker, it's more likely to be cancer.
Among the retrospective cases, the Roswell Park-developed PEER algorithm classified each one correctly as oncocytoma or ChRCC, except for four cancer cases that were misclassified by PEER as benign. Intriguingly, all four misclassified cases tested negative for the signature CD117 biomarker; among CD117-positive tumors, diagnosis using PEER was 100% accurate. In the prospective cohort, PEER was validated to have 100% diagnostic accuracy among 22 additional CD117-positive oncocytoma or ChRCC tumors. Furthermore, perfect accuracy was reproducible among different doctors who separately interpreted all CT scans.
"This new approach may finally allow reliable diagnosis of benign kidney tumors among the CD117-positive variants, which could prevent thousands of kidney tumor patients from undergoing unnecessary and often risky operations in the U.S. each year," says Dr. Kauffman.