Page 4 - 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

CN in patients with mRCC, and the findings suggest that CN does not provide a survival
advantage in a significant proportion of patients with mRCC.
In addition to this randomized trial, several retrospective observational studies have
investigated whether CN provides a survival advantage in patients receiving targeted
therapy [6-18]. These observational studies are limited to a varying degree by
heterogeneous patient populations, selection bias, confounding and as a result, the
strength of their evidence and related conclusions regarding the benefits of CN are
limited. Despite these limitations, nearly all available observational studies have
identified a significant survival advantage in favor of CN for patients treated with
targeted therapies [6-18]. For example, in a well performed analysis from the
International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) (one of
only two studies including Canadian patients), a 40% reduction in all-cause mortality was
noted among patients receiving CN after controlling for known biases and adjustment for
confounders [13]. Similar findings have been noted across many other multi-institutional
and population-based studies [6, 7, 9-12, 14-16, 18].
Overall, although CARMENA did not identify an overall survival advantage to CN,
the available evidence suggests that CN may provide a survival advantage in select
patients but not in all comers. Risk stratification and patient selection for CN remains
difficult. Multiple studies have investigated factors associated with both survival after CN
and response to CN[7, 8, 11-13, 17-32], and a nomogram has been developed and
externally validated to aid in the prediction of 6-month and 1-year survival after CN
using preoperative clinical variables[19, 33]. However, no validated models exist to
predict response to CN. Although the MSKCC[34] and the IMDC[35] prognostic models
are widely used to risk stratify patients with mRCC, and have been incorporated into
other professional society recommendations on CN[36], these models have also not been
validated to predict response to CN.
In patients with mRCC who are being considered for CN, the optimal timing relative
to the initiation of systemic therapy also remains controversial. Initiating systemic
therapy prior to CN may provide symptomatic control and disease stabilization or
regression for patients with a large tumor burden. In addition, treating patients with initial
systemic therapy may allow the identification of patients not likely to benefit from CN;
specifically, patients who progress rapidly on systemic therapy have a poor prognosis and
are unlikely to derive a survival advantage by undergoing CN. Approximately 30% of
patients who undergo initial targeted therapy prior to planned CN have been found
ultimately to not receive CN, with the most common reason being disease progression,
suggesting that a trial of initial targeted therapy may help select patients for CN[37-39].
The rationale for upfront CN is that it has the potential advantages of palliating symptoms
related to the primary tumor, elimination of a source of secondary metastases, and
improvement in host immune dysfunction. Although systemic therapy decreases the size