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
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