Brain Metastases in RCC: New Trials Reveal
How Discovery of Underlying Mechanisms, Novel Treatment
Approaches Could Improve a Dismal Prognosis
ntil recently, the exclusion of patients with brain metastases
from clinical trials on treatment of advanced
renal cell carcinoma hindered efforts to adequately evaluate
management approaches in this high-risk population.
The picture is changing, and with the publication of new information
from trials including these patients, an improved
understanding of how such resistant tumors may be treated is
emerging.
Although renal cell carcinoma (RCC) metastasizes less
often to the brain than to other sites, the poor prognosis
associated with a diagnosis of brain metastases in kidney
cancer has focused greater attention on the need to clarify
not only the epidemiology of this phenomenon but to
more clearly delineate underlying mechanisms and potential
therapies that could improve survival. Generally,
brain metastases are usually small and asymptomatic
when discovered on screening such as routine staging or
institution of systemic therapy. However, brain metastases
may present symptomatically and can be quite large.1
An estimated 64,000 new cases of kidney cancer were
diagnosed in the US in 2017, with approximately 14,400
deaths.2 A clear cell histology predominates in 70% to
80% of RCCs while subtypes other than clear cell include
papillary (10-15%) and chromophobe (5%). Although
RCC is typically localized at presentation (65% of cases),
in 35% of the cases, synchronous regional or distant metastases
are identified. Metachronus metastasis will develop
in approximately one-third of patients in whom RCC
is initially local. Studies within the last five years have
further clarified the epidemiology, pointing to lungs,
lymph nodes, liver, bone and brain as the most likely
sites.3
48 Kidney Cancer Journal
Epidemiology of Brain Metastases in RCC
A review of the International Metastatic Renal Cell Carcinoma
Database Consortium (IMDC) found that among
2027 patients with mRCC, the incidence of metastasis to
the brain was 8%, compared with 69% to the lungs, 43%
to the lymph nodes, 34% to the bones, and 19% to the
liver.3 Other studies have also reviewed the epidemiology
with similar results. For example, a population-based analysis
from Italy (n=11,157) and a global expanded-access
study (n=4543) showed that the incidence of brain metastases
ranged from 7% to 8%. They also confirmed that
specific sites of metastatic disease were also more associated
with brain metastasis: the rate of brain metastases was
2% in patients with abdominal metastases only vs 16%
in patients with thoracic and bone metastases.3
Further insights on epidemiology appeared in a report
by Sun et al4 who also provided perspectives on clinical,
patient, and sociodemographic characteristics of patients
presenting with primary RCC and brain metastases (BM)
at diagnosis. These authors used a nationally representative
cancer cohort originating from the US. While the global
incidence of BM at cancer diagnosis was 9.6%, in
descending order, its incidence varied according to primary
site: lung (20%), melanoma (6.9%), renal (6.5%),
breast (5.1%), and colon cancers (1.8%). Possibly with the
increased use of improved neuroimaging staging and
greater use of magnetic resonance imaging, the incidence
of BM is hypothesized to have increased in the last two
decades. There is a bit of a conundrum behind the supposed
increase in BM in kidney cancer patients. Sun et al
suggest that the increase is disconcerting, considering
that traditionally, such individuals have been excluded
from clinical trials
One of the intriguing aspects of the epidemiology papers
such as the report by Sun et al is the extent to which
they also explore the implications of emerging data for
prognosis in RCC patients with BM. Until recently, the
prognostic implications of this subset have not been well
delineated. Sun et al4 categorized patients based on clinical
risk factors they evaluated, including white/other race,
Jun Gong, MD
Medical Oncologist
Assistant Professor
Samuel Oschin Comprehensive
Cancer Institute at
Cedars-Sinai Medical Center
Los Angeles, California
U
Keywords: brain metastases, renal cell carcinoma, epidemiology,
mechanisms, tyrosine kinase inhibitors, cabozantinib, c-MET, PD-L1,
NIVOREN trial, checkpoint inhibitors.
Corresponding Author: Jun Gong, MD, Samuel Oschin Cancer Center,
8700 Beverly Blvd., Los Angeles, CA 90048.
Email address: jun.gong@cshs.org
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