Page 5 - Kidney Cancer Research Network of Canada (KCRNC) consensus statement on the role of cytoreductive nephrectomy for patients with metastatic renal cell carcinoma

CUAJ – Consensus Statement Mason et al
KCRNC consensus: Cytoreductive nephrectomy for mRCC

of the primary tumor in a proportion of patients [37, 40-43], the median decrease in size
is estimated to be between 7-32% and the clinical impact of this is questionable [37, 40-
43]. Furthermore, if the primary tumor increases in size or complexity during systemic
therapy, the feasibility of resection may be decreased.
To investigate the optimal timing of CN relative to initiation of systemic therapy, the
Immediate Surgery or Surgery After sunitinib Malate in Treating Patients With
Metastatic Kidney Cancer (SURTIME) trial, which was presented at the 2017 European
Society of Medical Oncology annual meeting, compared upfront CN versus sunitinib
followed by CN among patients with mRCC with a primary endpoint of disease
progression at 28 weeks[4]. Overall, the sequence of upfront CN or sunitinib did not
impact disease progression at 28 weeks of follow-up (42.0% versus 42.9%, respectively,
p >0.99) [4]. Although an advantage was seen in overall survival in the deferred CN
group (median OS 32.4 versus 15 months, p=0.034), it is difficult to interpret this result
in light of the underpowered analysis and the discordance with the disease progression
results. Indeed, SURTIME was complicated by significant difficulties with accrual, with
an initial target of 458 patients and a final accrual of 99 patients. Furthermore, the choice
of PFS as an endpoint represents an important flaw in the context of mRCC, where
documented OS benefits are ideally needed in testing of alternative treatment strategies.
As a result of these factors, the clinical impact of this trial is limited.
Several retrospective observational studies have investigated whether the timing of
CN versus systemic therapy impacts patient outcomes [9, 44, 45]. Two of these studies
found no difference in survival with initial CN versus initial targeted therapy[44, 45].
However, these sample sizes were relatively small (n=35 and n=102), limiting their
statistical power. A third more recent population-based study from the SEER database,
found an increased overall survival among patients receiving initial targeted therapy
followed by CN compared with the opposite. Finally, the most recent population based
analysis based on a very large patient sample from the United States National Cancer
Database found an overall survival benefit among patients with mRCC treated with CN
as the initial treatment modality [46].
Considering the available evidence, the results from CARMENA and SURTIME
show that systemic therapy should be the priority in patients with mRCC, with CN
reserved for very select patients. Recognizing the limitations of the existing data on CN
in patients with mRCC, we provide the following recommendations, based on expert
consensus.
As advanced kidney cancer management is complex and rapidly evolving, decisions
regarding the optimal timing of CN should ideally be made after appropriate
multidisciplinary discussions and should be followed by a detailed and thorough
informed consent process.