Brain Metastases Occur in Significant Percentage of Advanced RCC, Underscoring Potential Role for Routine Brain Imaging

Ritesh R. Kotecha, MD

Brain imaging should be considered for patients with advanced or metastatic renal cell carcinoma (mRCC) who have a high metastatic burden and who have progressed after treatment with first-line therapies, according to data published in the Journal of the National Comprehensive Cancer Network.¹

Results from a large multi-institutional cohort study found that 4.3% (95% CI, 3.3%-5.3%; n = 72) of 1689 patients with mRCC had incidental brain metastases without documented neurological symptoms. The median overall survival (OS) in these patients was 10.3 months (range, 7.0-17.9) and the 1-year OS rate was 48% (95% CI, 37%-62%).

When stratified by International Metastatic RCC Database Consortium (IMDC) risk status, survival outcomes were not found to significantly differ between those with favorable-, intermediate-, or poor-risk patients vs the use of log-rank testing (P = .3). The median OS in the favorable-risk, intermediate-risk, and poor-risk subgroups was 12.7 months (range, 4.8–not evaluable [NE]), 12.4 months (range, 7.4-19.7), and 4.5 months (range, 3.8–NE), respectively. The 1-year OS probability of favorable-, intermediate-, and poor-risk disease was 53% (95% CI, 33%-86%), 52% (95% CI, 38%-71%), and 29% (95% CI, 9%-92%), respectively.

“With 4% overall incidence in this cohort, one might conclude that baseline brain imaging should be considered in all patients with metastatic kidney cancer, particularly those with multiorgan involvement and/or pulmonary metastases” lead study author Ritesh R. Kotecha, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, stated in a press release.²

Although brain metastases occur in approximately 5% to 20% of patients with mRCC, no standard guidelines exist for brain imaging in the absence of symptoms. As such, asymptomatic patients may not be included in historical rates, making this population difficult to define. Earlier detection of brain metastases through standardized screening guidelines could help to solidify the rates among patients with mRCC, as well as improve survival outcomes.

To characterize those with mRCC who were diagnosed with asymptomatic brain metastases, investigators performed a retrospective review of data from patients who were screened prior to entering clinical trials. Data from 68 clinical trials performed at Memorial Sloan Kettering Cancer Center and Gustave Roussy between 2001 and 2019 were reviewed and utilized to evaluate baseline characteristics, as well as reported symptoms. Any clinical trials that did not require brain imaging for participation were not reviewed.

“Brain imaging is routinely obtained for [patients with] kidney cancer with symptoms that suggest central nervous system [CNS] metastases, but none of the patients with brain metastases included here were symptomatic,” senior researcher Martin H. Voss, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, stated in the release. “In current practice, the chest, abdomen, and pelvis are routinely imaged from the time that metastatic disease is first detected, yet many oncologists do not image the brain.”

Of the 72 patients found to have incidental brain metastases without neurologic symptoms, the median age at the time of cancer diagnosis was 56 years (range, 37-77) and 75% of patients were male. Additionally, 88% (n = 63) of patients had undergone prior nephrectomy, and 68% had received at least 1 prior line of treatment. All patients had a clear cell histologic subtype, and 60% (n = 43) presented with stage IV disease at initial diagnosis. In terms of brain metastases characteristics, 63% (n = 45) of patients had a solitary lesion, and CNS involvement was multifocal in 38.5% of patients.

Among the 72 patients reviewed, 61 had additional follow-up data that indicated they received brain metastases site-directed therapy. Of those patients, 83% (n = 52) received a corticosteroid, and 93% (n = 57) underwent site-specific therapy, such as stereotactic radiotherapy (72%), whole-brain radiotherapy (14%), surgical resection (11%), or both radiotherapy and resection (4%). Moreover, the median time between brain imaging and site-directed therapy was 30 days (range, 4-262).

Additional data indicated that OS was not found to differ significantly in patients with solitary disease vs those with multifocal disease. The median OS for patients with solitary disease was 14.2 months (range, 9.5-21.6) vs 5.8 months (range, 4.1-18 months) for those with multifocal disease; the 1-year OS probability rates were 57% (95% CI, 44%-74%) and 33% (95% CI, 19%-58%), respectively. Difference across other subgroups, including lesion size, also did not show statistical differences.

“The findings in this study are important for 2 reasons. First, they show that the overall prognosis of patients with brain metastases is consistently worse than the broader population of patients with metastatic renal cell carcinoma. We need to develop a deeper scientific understanding of why this patient population has a worse outcome, and we need to include them in future clinical trials,” Eric Jonasch, MD, a professor of Genitourinary Medical Oncology at The University of Texas MD Anderson Cancer Center, stated in the release. “Second, they underscore the utility for MRI imaging of all patients with metastatic renal cell carcinoma both at initial diagnosis, and at regular intervals, to detect occult brain metastases, since specific treatment strategies are required for this patient population.”

References

1. Kotecha RR, Flippot R, Nortman T, et al. Prognosis of incidental brain metastases in patients with advanced renal cell carcinoma. J Natl Canc Netw. 2021;19(4):432-438. doi:10.6004/jnccn.2020.7634
2. JNCCN study: important potential role for routine brain imaging in advanced kidney cancer. News release. The National Comprehensive Cancer Network. April 13, 2021. Accessed April 22, 2021. https://bit.ly/2PcPYiD