Page 3 - Kidney Cancer Research Network of Canada (KCRNC) consensus statement on the role of cytoreductive nephrectomy for patients with metastatic renal cell carcinoma
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CUAJ – Consensus Statement Mason et al
KCRNC consensus: Cytoreductive nephrectomy for mRCC
Should patients with metastatic renal cell carcinoma be offered cytoreductive
nephrectomy and what is the optimal patient selection and timing?
1. Recognizing the complex nature of advanced kidney cancer management,
decisions regarding CN should ideally be made in a multidisciplinary setting.
2. Patients with a good performance status (ECOG ≤1 or KPS ≥ 80%), minimal
symptoms related to metastases, a resectable primary tumor, and a limited burden
of metastatic disease should be offered upfront CN followed by metastases
directed therapy, a period of surveillance or systemic therapy.
3. Patients with significant systemic symptoms from metastatic disease, active
central nervous system metastases, a limited burden of disease within the kidney
relative to the cumulative extra -renal volume of metastases, rapidly progressing
disease, a poor performance status (ECOG >1 or KPS < 80%), and/or limited life
expectancy should not undergo CN.
4. Patients with mRCC but without characteristics of (2) or (3) should be offered
initial treatment with systemic therapy with consideration of CN given to those
with a significant clinical response.
Beyond the clinical trials performed prior to the modern era, several recent studies
have investigated the role of CN in patients receiving targeted therapy. The Clinical Trial
to Assess the Importance of Nephrectomy (CARMENA) randomized patients with
mRCC to CN followed by sunitinib therapy or sunitinib without CN[3]. Contrary to the
clinical trials performed in the pre-targeted therapy era, CARMENA did not identify a
survival advantage to undergoing CN prior to systemic therapy. Including 452 patients
with a median follow-up 50.2 months, sunitinib alone was found to be non-inferior to CN
followed by sunitinib with regards to overall survival (HR 0.89; 95% CI 0.71 – 1.10).
Furthermore, no significant difference was identified in progression-free survival or
response to treatment. There are noteworthy limitations to this trial. Most importantly,
44% of patients included in CARMENA had poor-risk disease as classified by the
Memorial Sloan Kettering Cancer Center (MSKCC) Prognostic Model and the remaining
patients had intermediate risk disease. This trial was not designed to test whether CN
provides a survival advantage among mRCC patients with favorable risk characteristics.
CARMENA accrued 21% less patients than initially planned over a long time period (8
years) casting some statistical doubt on the results. Furthermore, systemic therapy in
CARMENA consisted of sunitinib whereas the first line systemic treatment for mRCC
continues to evolve with the use of different targeted therapies and combinations of
checkpoint inhibitors proven more active than sunitinib for intermediate and poor risk
patients [5]. These limitations notwithstanding, CARMENA is the best available data on