Prognosis of Incidental Brain Metastases in Patients With Advanced Renal Cell Carcinoma

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  • 1 Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York;
  • 2 Department of Cancer Medicine, Gustave Roussy, Paris-Saclay University, Villejuif, France;
  • 3 Department of Oncology and Hematology, University of Modena and Reggio Emilia, Modena, Italy; and
  • 4 Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
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Background: Metastatic renal cell carcinoma (mRCC) management guidelines recommend brain imaging if clinically indicated and the rate of occult central nervous system (CNS) metastasis is not well-defined. Early detection could have major therapeutic implications, because timely interventions may limit morbidity and mortality. Patients and Methods: A retrospective review was performed to characterize patients with mRCC incidentally diagnosed with asymptomatic brain metastases during screening for clinical trial participation at Gustave Roussy and Memorial Sloan Kettering Cancer Center. Descriptive statistics and time-to-event methods were used to evaluate the cohort. Results: Across 68 clinical trials conducted between 2001 and 2019 with a median 14.1-month follow-up, 72 of 1,689 patients (4.3%) with mRCC harbored occult brain metastases. The International Metastatic RCC Database Consortium (IMDC) risk status was favorable (26%), intermediate (61%), and poor (13%), and 86% of patients had ≥2 extracranial sites of disease, including lung metastases in 92% of patients. CNS involvement was multifocal in 38.5% of patients, and the largest brain metastasis was >1 cm in diameter in 40% of the cohort. Localized brain-directed therapy was pursued in 93% of patients, predominantly radiotherapy. Median overall survival was 10.3 months (range, 7.0–17.9 months), and the 1-year overall survival probability was 48% (95% CI, 37%–62%). IMDC risk and number or size of lesions did not correlate with survival (log-rank, P=.3, P=.25, and P=.067, respectively). Conclusions: This large multi-institutional mRCC cohort study identified occult brain metastasis in a notable proportion of patients (4.3%) and highlights that the risk of asymptomatic CNS involvement extends to those with favorable risk features per IMDC risk assessment. These data provide rationale for brain screening in patients with advanced RCC.

Submitted June 29, 2020; accepted for publication August 4, 2020. Published online February 12, 2021.

Author contributions: Study concept: Kotecha, Escudier, Motzer, Albiges, Voss. Study design: Kotecha, Flippot, Escudier, Motzer, Albiges, Voss. Data acquisition: Kotecha, Flippot, Nortman, Guida. Quality control of data and algorithms: Kotecha, Flippot, Albiges, Voss. Data analysis and interpretation: Kotecha, Flippot, Escudier, Motzer, Albiges, Voss. Statistical analyses: Kotecha, Flippot, Patil. Manuscript preparation: Kotecha, Flippot, Escudier, Motzer, Albiges, Voss. Critical revision: All authors.

Disclosures: Dr. Escudier has disclosed that he is a scientific advisor for Novartis, Pfizer, Bristol-Myers Squibb, Ipsen, EUSA Pharma, AVEO, and Genentech; receives honoraria from Pfizer, Novartis, Bristol-Myers Squibb, Ipsen, Genentech, EUSA Pharma; and receives consulting fees from Bristol-Myers Squibb, Pfizer, Genentech, and Ipsen. Dr. Motzer has disclosed that he receives consulting fees from Pfizer, Eisai, Merck, Genentech (Roche), and Novartis. Dr. Albiges has disclosed that he is a scientific advisor for Novartis, Amgen, Bristol-Myers Squibb, Ipsen, Roche, Novartis, Pfizer, Astellas Pharma, and Merck. Dr. Voss has disclosed that he receives grant/research support from Bristol-Myers Squibb, Pfizer, and Genentech; is a scientific advisor for Alexion Pharmaceuticals, Calithera Biosciences, Corvus Pharmaceuticals, Exelixis, Eisai, Natera, Novartis, and Pfizer; receives consulting fees from Eisai and Takeda; and receives honoraria from Novartis. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Martin H. Voss, MD, Department of Medicine, Memorial Sloan Kettering Cancer Center, 300 East 66th Street, Box 138, New York, NY 10065. Email: vossm@mskcc.org
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