Current Guidelines for Treating Oligometastatic RCC:
An Ever-changing Paradigm Integrates New Strategies
his review provides an update on emerging data from
current literature on the treatment of oligometastatic
renal cell carcinoma. A rapidly evolving paradigm of
treatment reflects multimodal approaches ranging from active
surveillance to combinations of stereotactic radiotherapy and
systemic therapies. Guidelines for determining optimal choices
are presented.
Oligometastatic disease can be conceptualized as an intermediate
state between limited, organ-confined primary
cancer and diffuse, polymetastatic disease. Oligo,
which means few or scanty, is derived from the Greek
“oligos.” For clinicians, the term refers to a limited
tumor burden potentially amenable to local treatment
approaches, and a number of studies have redefined this
definition over 25 years.1-3 When first used, the term referred
to a state of limited metastatic burden, where some
patients may be amenable to cure if all known metastatic
deposits can be extirpated or ablated, and further distant
progression delayed or avoided altogether.1 A more quantitative
definition of the oligometastatic state suggests
up to three or up to five lesions, by various accounts.
Oligometastases may be present at the initial time of diagnosis
of the primary tumor (called synchronous), or
separated by an interval of time for recurrence since the
initial diagnosis or treatment of the primary tumor
(called metachronous). Metachronous oligometastases,
particularly those with a long delay in the time to recurrence,
are generally thought to have a better prognosis
than tumors with metastatic disease at the time of presentation.
42 Kidney Cancer Journal
Clear cell renal cell carcinoma (ccRCC) is capable of
both lymphatic and hematogenous spread, and has been
noted to have the ability to spread to nearly every possible
site in the body. Historically, it was noted that a small
subset of patients presented with an indolent form of advanced
disease in which surgical resection of small volume
metastatic deposits led to serial, protracted disease
free intervals, lending early support to the concept of
metastasectomy. These early clinical observations have
recently been supported by modern, large-scale genomic
sequencing initiatives that have defined the genetic underpinnings
for the diversity of metastatic phenotypes.
These patterns of spread range from rapid and simultaneous
metastatic dissemination to multiple tissue sites,
to a highly attenuated pattern characterized by slower
progression to solitary or oligometastatic disease. The
most extreme such presentation being described comprises
a protracted latency of up to two decades as a feature
of tumors that metastasize to the pancreas.4 While
the hallmark genomic drivers of ccRCC metastases appear
to be loss of chromosomes 9p and 14q,4-6 cases that
are multi-site rapid progressors are characterized by VHL
wildtype and BAP1 driven evolutionary subtypes.4 On
the other hand, tumors that display a more attenuated
phenotype of spread appear to harbor clones with
PBRM1 mutations.4
The treatment paradigm for oligometastatic renal cell
carcinoma (RCC) has moved in multiple directions beyond
just surgery, especially in the post-cytokine era, as
new treatments have vastly expanded the armamentarium
and debunked earlier concepts of how outcomes can
be improved. One of the concepts discarded from earlier
studies was that oligometastatic RCC represents a radiation
resistant malignancy, showing a high degree of resistance
to conventionally fractionated radiation
therapy. Stereotactic body radiotherapy (SBRT) has been
increasingly utilized for treatment of metastatic sites
with high local control rates and low toxicity.
Alexandra Drakaki, MD, PhD
Assistant Professor of Medicine
(Hematology/Oncology) and Urology
Medical Director of the GU Oncology
Program at the Institute of Urologic
Oncology at UCLA
Los Angeles, California
Allan J. Pantuck, MD, MS, FACS
Professor and Vice Chair for Academic Affairs
Department of Urology
UCLA Institute for Urologic Oncology
Los Angeles, California
Keywords: oligometastases, renal cell carcinoma, ablation, radiotherapy,
metastasectomy, nephrectomy, active surveillance, SBRT, IMDC
risk factors, systemic therapy.
Corresponding Author: Allan J. Pantuck, MD, University of California,
Los Angeles, 200, Medical Plaza Driveway Suite 140, Los Angeles, CA
90095; Phone: (310) 794-7700. Email: APantuck@mednet.ucla.edu
Albert J. Chang, MD
Associate Professor, Vice Chair of Surgical Services
and Brachytherapy Service Chief
Department of Radiation Oncology
David Geffen School of Medicine at UCLA
and UCLA Institute for Urologic Oncology
Los Angeles, California
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