Circulating Tumor DNA May Have Prognostic Value in Kidney Cancer

Among patients with metastatic renal cell carcinoma (mRCC), serial tumor-informed circulating tumor DNA (ctDNA) negativity or clearance was associated with improved outcomes when compared with patients who became or were persistently ctDNA positive, researchers have found.

“In the surveillance setting, ctDNA positivity was strongly predictive of [progressive disease] in patients with mRCC, whereas nearly all of the serially ctDNA-negative patients remained progression free during follow-up,” researchers noted in study findings published in JCO Precision Oncology. “This latter observation has particular clinical significance, providing evidence to support intermittent treatment breaks in the setting of mRCC.”

According to the National Cancer Institute, ctDNA is a term used to refer to small pieces of DNA that are released into a patient’s blood by tumor cells after they die. A sample of blood can be utilized to look for and measure the amount of ctDNA and identify specific mutations in the DNA.

Investigators evaluated 490 plasma samples from 92 patients, including those with both clear cell and non-clear cell subtypes of RCC (79.3% ccRCC, 14.1% nccRCC and 6.5% unclassified). At a median follow-up of 10 months, ctDNA dynamics were assessed in 56 patients on treatment and ctDNA status was analyzed in a 32-patient surveillance cohort, researchers reported.

Patients who became or were persistently ctDNA-positive had a 220% higher risk of experiencing disease progression or death compared with those with serial ctDNA negativity or clearance. Additionaly, in the surveillance cohort of patients with persistent ctDNA positivity were 18 times more likely to experience disease progression or death, according to the study’s findings.

“ctDNA has been controversial in kidney cancer in the past,” study co-author Dr. Alan Tan told CURE® in an interview. “It’s known to be one of the lower-shedding solid tumor types, and so not many people are doing ctDNA to make decisions in kidney cancer. And I don't think the take home message [of the study] is to do it on everybody and try to make decisions based on it, but I think the take home point is it's very prognostic.”

Tan is the GU Oncology Lead at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, as well as an associate professor in the Division of Hematology/Oncology at Vanderbilt University Medical Center and GU Executive Officer with the Alliance for Clinical Trials in Oncology. He spoke with CURE® about the trial and the significance of its findings.

Transcript:

ctDNA has been controversial in kidney cancer in the past. It’s known to be one of the lower-shedding solid tumor types, so not many people are doing ctDNA to make decisions in kidney cancer. I don't think the take home message [of the study] is to do it on everybody and try to make decisions based on it, but the take home point is it's very prognostic. If you look at the publication that we just had in JCO Precision Oncology, we had close to 100 patients in the study. If you're ctDNA-positive at any time point, your progression free survival is significantly worse. If you remain serially ctDNA-negative, then your survival is much better.

Transcript has been edited for clarity and conciseness.

Reference:

“Longitudinal Testing of Circulating Tumor DNA in Patients With Metastatic Renal Cell Carcinoma” by Dr. Arnab Basu et al., JCO Precision Oncology.

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