Metastatic Renal Cell Carcinoma: Watch for Brain Mets

MIAMI -- Roughly one in 20 patients with metastatic renal cell carcinoma (RCC) have asymptomatic brain metastases at diagnosis, a retrospective analysis of nearly 70 clinical trials found.

In close to 1,600 patients evaluated, 4.5% were found to have occult brain lesions at trial enrollment, and this was seen across all International Metastatic RCC Database Consortium (IMDC) risk categories, reported Ritesh Kotecha, MD, of Memorial Sloan Kettering Cancer Center in New York City.

The 12-month overall survival (OS) probability was 48% for this group of patients, with an estimated median OS of 10.3 months, according to the findings presented at the International Kidney Cancer Symposium.

"Current management guidelines for systemic practice for brain metastatic assessment is really not standard. Clinicians are sort of reliant on patients to present with neurologic symptoms to basically decide whether to do screening," Kotecha said. "Early detection can potentially allow for early intervention, which may impact morbidity and mortality, and specifically in the brain metastatic population."

By IMDC criteria, 26% of the patients' brain lesions identified had favorable-risk RCC, 61% had intermediate-risk disease, and 13% had poor-risk disease. The 1-year OS rates and median survival for each of these risk groups were:

• Favorable: 64%, 12.7 months
• Intermediate: 62%, 12.5 months
• Poor: 35%, 4.4 months

"In this heterogeneous group of patients, application of IMDC risk alone is fairly limited, and other metrics, including size and focality actually might be more key," Kotecha explained.

Patients with solitary lesions (68.5%) had a median OS of 14.2 months, as compared with 5.8 months for those with multifocal lesions (38.5%). The 1-year OS rates were 57% and 33% for these two groups, respectively. Patients with three or more lesions had a 1-year OS of 21%.

Examining survival by the size of the largest brain lesion, median OS was 19 months for patients with a solitary lesion <1 cm and 14 months for those with a single lesion >1 cm. For patients with multifocal disease, median OS was 6 months in patients whose largest lesion was <1 cm and 6.5 months for those whose largest lesion was >1 cm.

"There was associated edema present radiographically in almost 80% of patients," Kotecha said. "On chart review, we looked particularly to make sure that these patients were asymptomatic at study screening for any neurologic symptoms."

For their analysis, his group examined data on 68 clinical trials conducted from 2001 to 2019 that had mandatory baseline brain imaging at study entry, which in total involved 1,597 patients with metastatic clear cell RCC. Ultimately, they identified 72 patients with incidental brain metastases, three-fourths of whom were men. In 60%, the largest lesion was ≤1 cm. Most patients had had a prior nephrectomy (88%), and sarcomatoid features were present in 11%.

Median patient age in the cohort was 56, and 60% had stage IV disease at diagnosis. Most patients had a high degree of metastatic burden, with 86% having two or more extracranial lesions. Lung was the predominant site (92%) of these, followed by the liver and bone (25% each).

Following diagnosis of their cranial lesions, most patients were administered corticosteroids (83%) and received some sort of local therapy (93%):

• Stereotactic radiosurgery: 67%
• Whole-brain radiotherapy: 13%
• Surgery: 10%
• Surgery plus radiotherapy: 3%

Median time between diagnosis and site-directed therapy was 30 days.

Regarding treatment history, 32% were naive to systemic therapy, 43% had one prior regimen, and 25% had two or more prior regimens.