of metastases.11 The four most common metastatic sites for
RCC are lung, bone, non-regional lymph nodes, and liver.
Pulmonary metastases. SM is most commonly performed
for patients having a limited number of unilateral
pulmonary metastases. Patients with disease limited
to the lung are the best responders to cytokine or targeted
therapy.14 Although many studies have reported
clinical benefit for pulmonary lesions, a poor prognosis
is more likely to be observed in patients with a higher
number of lesions, concomitant mediastinal nodal
metastases, and incomplete resection.
Bone metastases. As the second most common
metastatic site in mRCC, lesions to the spine are the most
affected bone site. Excisional surgery of bone metastases
is an extraordinary and technically demanding procedure
because the metastases are hypervascular and destructive,
with reconstruction further complicating the
likelihood for a successful outcome. In view of the negative
impact of complication after SM in bone and brain
metastases, SBRT may represent an alternative option to
improve treatment options in these patients.
Lymph nodes, liver and pancreatic metastases. The
data are sparse on these metastatic sites, particularly for
isolated lymph nodes. The guideline from Kato et al is
that SM for these lesions should be carefully considered
in patients with good performance status and completely
resectable solitary metastases.15 RCC tumors spread rarely
to the pancreas, but when they do, they represent solitary
metastatic involvement in up to half of these cases.16
This fact, combined with the often attenuated and delayed
pattern of spread noted above, supports surgical resection
as an option with durable long term survival in
surgically amenable cases.
The controversy surrounding the benefit of SM is
largely due to the lack of high-level evidence on its role
in terms of improving survival in the era of systemic
therapy. No randomized trials have evaluated the role of
complete SM, although many observational studies have
suggested a survival benefit of an aggressive surgical approach.
17 A systematic review of the literature derived
from 56 retrospective studies in Embase and Medline
databases offers valuable insights, however, with regard
to prognostic factors to consider in clinical decision making
when patients may be candidates for SM. Median
overall survival in this review by Ouzaid et al17 ranged
from 36 to 1432 months for those undergoing SM vs 8
to 27 months when SM was not performed. The most
important prognostic factor for OS was complete resection
of metastases. Other prognostic factors included disease
free survival from nephrectomy, primary tumor
features (T stage 3 or more, high grade, sarcomatoid features,
and pathological status), the number of metastases,
and performance status. Survival benefit was most apparent
with lung metastasectomy.
Concluding that only a small subgroup of patients
may benefit from SM, Ouzaid17 nevertheless suggest it is
a worthwhile option to consider, reiterating the conventional
wisdom that the best candidates are those with
good performance status, a long time interval with no
evidence of disease, a relatively limited burden of disease
(ideally a solitary metastasis), and achievable metastasesfree
status. Confirming what almost every series in the
44 Kidney Cancer Journal
literature has observed, the review suggests that patients
with synchronous metastases have worse prognosis.
Some sites—such as brain and liver—are also associated
with a poor prognosis and SM in this subset may not provide
potential benefit.
An intriguing question raised by the literature is to
what extent outcomes may be influenced by more specific
secondary analyses following cytoreductive nephrectomy
for oligometastatic RCC. A case in point: a
study by Pierorazio et al18 who examined whether outcomes
could be predicted based on the fractional percentage
of tumor removed (FPTV). Few studies have
followed up on the hypothesis raised by this report, but
the authors suggest some significant results: 55 patients
had their FPTV calculated; 45 had >90% FPTV. The median
disease-specific survival times were 11.6 and 2.9
months for patients with >90% and <90% FPTV removed
(P=0.002).
The value of this provocative study also lies in its hypothesis
generating aspects. Although FPTV may not be
the primary explanation for the discrepancy in survival,
this measure could be an easy-to-calculate surrogate for
complex factors driving the survival benefit in patients
who had higher results for FPTV. Thus, the FPTV criteria
could allow surgeons to easily identify patients who will
benefit from cytoreductive surgery without using complex
performance scales or nomograms.
Active Surveillance: When Can Immediate
Aggressive Treatment be Delayed?
With the publication of a pivotal, prospective, Phase 2
trial by Rini et al19 in 2016, the concept of active surveillance
began to undergo more consideration as a viable
approach. This study encouraged further investigations
that also undercut the widely held perception that tumors
needed to be treated immediately and aggressively.
Since the publication of the Rini paper, a significant shift
in thinking, including guidelines issued by the European
Society for Medical Oncology, have had a sharp impact
on treatment approaches.20
Among the salient factors accounting for this change
in rationale is the paradigm of risk stratification from the
International Metastatic Renal Cell Carcinoma Database
Consortium (IMDC). Rini et al19 relied on tis classification
scheme to propose that AS may be an acceptable option.
Patients can be classified into good, intermediate,
or poor prognosis according to:
• Time from diagnosis to treatment (<1 year).
• Karnofsky performance status (<80%).
• Anemia
• Hypercalcemia
• Thrombophilia
• Neutrophilia
The absence of all previous parameters identifies patients
in a favorable risk group; the presence of one or
two, and at least 3 prognostic factors classifies patients
into intermediate and poor-risk categories, respectively.
The ESMO guidelines introduced the possibility of managing
selected patients with favorable disease using AS.
The Rini study has been touted as the study with the best
available evidence; 48 patients with treatment-naïve,