Kidney Cancer Journal 43
Metastatic RCC accounts for up to 25-30% of patients
at diagnosis and leads to death in most cases.7 Additional
studies from that period pointed toward a poor prognosis
for patients with oligometastatic RCC, with a 5-year survival
rate of <10%.8 As part of their identifying the challenges
in the pre-cytokine era, these reports also
examined other issues, for example, whether the number
of metastatic sites rather than location dictated overall
survival in oligometastatic RCC. One of these reports by
Han et al,9 found that oligometastatic RCC confined to
only one organ site had a better prognosis than RCC in
multiple organs. Survival in patients with disease limited
to the lung was similar to that of patients whose disease
was limited to bone.
This early pivotal retrospective study is important for
other reasons, offering a benchmark for how much more
information was needed at the time (2003) on the treatment
of oligometastatic RCC and suggesting how future
reports would explore more precisely emerging data. For
example, Han et al9 urged physicians to consider enrolling
patients with multiple organ involvement into
clinical trials because these patients appear to have a
lower response rate to immunotherapy. It would be years
after this published study that immunotherapy would
begin to have a much more robust influence on the treatment
of oligometastatic RCC in patients with multiple
organ involvement and it is intriguing to consider how
much the treatment algorithm has changed in the postcytokine
environment and the advent of checkpoint inhibitors.
Since then new concepts about treatment have ushered
in a dramatically different era, albeit with its own
set of new challenges. But unlike the challenges of
decades ago when oligometastatic RCC was perceived as
largely radioresistant, new challenges have emerged.
These challenges are driven by advances in targeted therapies,
the use of immune checkpoint inhibitors, and perhaps
most significantly, the application of stereotactic
body radiation therapy (SBRT) for oligometastatic RCC,
thus improving outcomes in an otherwise radioresistant
malignancy.
Challenging Choices in Treatment
These new challenges, however, are more related to our
ability to sort through and resolve many issues and questions
related to an abundance of data affecting our
choices—whether to treat the tumors as metastatic or
local disease, should it be removed, radiated, or observed?
In evaluating our choices, we need to determine
criteria for selection of appropriate candidates for surgical
metastasectomy, understand the safety of combining
SBRT with TKI agents and checkpoint inhibitors, assess
the extent to which patients can undergo active surveillance
as opposed to upfront systemic therapy, determine
what time between nephrectomy and recurrence of RCC
could be an indicator for observation, and consider how
unique metastatic site influences the symptoms, deterioration
of general condition and activities of daily living.
In addressing these issues, this review will focus on
the most recent papers in the field and how emerging
data could reshape treatment rationale. One of the controversies
addressed extensively has been the role of
complete surgical metastasectomy of RCC in the postcytokine
era. This is important in view of the fact that
data supporting complete metastasectomy (CM) were derived
primarily from the era of cytokine therapy.10 Studies
like those of Lyon et al addressed whether complete
metastasectomy remains beneficial in patients who receive
more recently approved systemic therapies. In
doing so, they examined survival outcomes among patients
treated with CM in the era of targeted therapy and
checkpoint blockade availability.
Lyon et al identified 586 patients who underwent partial
or radical nephrectomy of unilateral, sporadic renal
cell carcinoma with a first occurrence of metastasis between
2006 and 2017. Of these patients 158 were treated
with complete metastasectomy. The authors observed
that CM was associated with improved CSS and OS compared
to incomplete or no CM in the era of targeted therapy
and checkpoint blockade availability. This associa-
tion persisted after adjusting for the timing, location and
number of metastases and it was observed in the context
of 93% of patients who underwent CM but did not receive
systemic treatment of the index metastasis.10
These data suggest that CM should continue to have
a role in the management of oligometastatic RCC despite
the improved efficacy of targeted therapies and checkpoint
inhibitors relative to previously available systemic
agents. Careful patient selection for this approach remains
key. In this series most patients chosen for CM
had a solitary metastasis and a prolonged disease-free interval
between nephrectomy and metastasis development,
consistent with known prognostic features of CM.
Moreover, a strategy of CM followed by observation has
the potential advantage of sparing patients the additional
morbidity of systemic agents while preserving the
efficacy of these agents for use later in the disease
process.
Emphasizing that careful patient selection for SM is
essential, Kato et al.11 analyzed a host of factors all of
which should be considered when determining which
patients are candidates for surgery. Reviewing the literature
in an editorial commentary, Kata et al cited numerous
articles pointing toward a general consensus on
clinical and pathological factors, including: performance
status, disease-free interval, abnormal laboratory data,
and sites of metastases, Fuhrman grade, and risk category
in prognostic models. Acknowledging reports that complications
and in-hospital mortality rates are not negligible
in patients treated with targeted therapy who
undergo surgical resection.12, 13 Kato et al identified patients
with a good indication for SM of RCC. These patients
should have the following features:
• Solitary or oligometastatic lesions.
• Symptomatic metastases deteriorating activities
of daily living and/or quality of life.
• Resistance to radiotherapy and/or recently
developed systemic therapies.
• Easy surgical accessibility and resectability with a
lower rate of complications.
Surgical Metastasectomy: Site-specific Clinical Factors
Treatment strategies may be influenced by site-specific
clinical factors with prognostic value for local treatment