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      Comparison of Immediate vs Deferred Cytoreductive Nephrectomy in Patients with Synchronous Metastatic Renal Cell Carcinoma Receiving Sunitinib : The SURTIME Randomized Clinical Trial

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          Abstract

          In clinical practice, patients with primary metastatic renal cell carcinoma (mRCC) have been offered cytoreductive nephrectomy (CN) followed by targeted therapy, but the optimal sequence of surgery and systemic therapy is unknown.

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          Most cited references18

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          Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study.

          There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (RCC) treated with vascular endothelial growth factor (VEGF) -targeted therapy. Baseline characteristics and outcomes on 645 patients with anti-VEGF therapy-naïve metastatic RCC were collected from three US and four Canadian cancer centers. Cox proportional hazards regression, followed by bootstrap validation, was used to identify independent prognostic factors for OS. The median OS for the whole cohort was 22 months (95% CI, 20.2 to 26.5 months), and the median follow-up was 24.5 months. Overall, 396, 200, and 49 patients were treated with sunitinib, sorafenib, and bevacizumab, respectively. Four of the five adverse prognostic factors according to the Memorial Sloan-Kettering Cancer Center (MSKCC) were independent predictors of short survival: hemoglobin less than the lower limit of normal (P < .0001), corrected calcium greater than the upper limit of normal (ULN; P = .0006), Karnofsky performance status less than 80% (P < .0001), and time from diagnosis to treatment of less than 1 year (P = .01). In addition, neutrophils greater than the ULN (P < .0001) and platelets greater than the ULN (P = .01) were independent adverse prognostic factors. Patients were segregated into three risk categories: the favorable-risk group (no prognostic factors; n = 133), in which median OS (mOS) was not reached and 2-year OS (2y OS) was 75%; the intermediate-risk group (one or two prognostic factors; n = 301), in which mOS was 27 months and 2y OS was 53%; and the poor-risk group (three to six prognostic factors; n = 152), in which mOS was 8.8 months and 2y OS was 7% (log-rank P < .0001). The C-index was 0.73. This model validates components of the MSKCC model with the addition of platelet and neutrophil counts and can be incorporated into patient care and into clinical trials that use VEGF-targeted agents.
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            Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal

            Summary Clear-cell renal cell carcinoma (ccRCC) exhibits a broad range of metastatic phenotypes that have not been systematically studied to date. Here, we analyzed 575 primary and 335 metastatic biopsies across 100 patients with metastatic ccRCC, including two cases sampledat post-mortem. Metastatic competence was afforded by chromosome complexity, and we identify 9p loss as a highly selected event driving metastasis and ccRCC-related mortality (p = 0.0014). Distinct patterns of metastatic dissemination were observed, including rapid progression to multiple tissue sites seeded by primary tumors of monoclonal structure. By contrast, we observed attenuated progression in cases characterized by high primary tumor heterogeneity, with metastatic competence acquired gradually and initial progression to solitary metastasis. Finally, we observed early divergence of primitive ancestral clones and protracted latency of up to two decades as a feature of pancreatic metastases.
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              Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma

              Cytoreductive nephrectomy has been the standard of care in metastatic renal-cell carcinoma for 20 years, supported by randomized trials and large, retrospective studies. However, the efficacy of targeted therapies has challenged this standard. We assessed the role of nephrectomy in patients with metastatic renal-cell carcinoma who were receiving targeted therapies.
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                Author and article information

                Journal
                JAMA Oncology
                JAMA Oncol
                American Medical Association (AMA)
                2374-2437
                December 13 2018
                Affiliations
                [1 ]The Netherlands Cancer Institute, Amsterdam, the Netherlands
                [2 ]Department of Urology, Radboud University Hospital, Nijmegen, the Netherlands
                [3 ]Department of Urology, Princess Margaret Hospital, Toronto, Ontario, Canada
                [4 ]Department of Oncology, Cardiff Hospital, Wales, United Kingdom
                [5 ]Department of Urology, Institut Jules Bordet, Brussels, Belgium
                [6 ]Department of Urology, Amsterdam Medical Center, Amsterdam University, Amsterdam, the Netherlands
                [7 ]Division of Medical Oncology, QEII Health Sciences Center, Halifax, Nova Scotia, Canada
                [8 ]Department of Urology, Saint Antonius Hospital, Nieuwegein, the Netherlands
                [9 ]Department of Oncology, Maastricht University Medical Center, Maastricht, the Netherlands
                [10 ]Department of Surgery-Urology, University of Montreal Hospital Center, Quebec, Ontario, Canada
                [11 ]Department of Oncology, The Royal Free Hospital and Queen Mary University, London, United Kingdom
                [12 ]Department of Urology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
                [13 ]Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium
                [14 ]Department of Urology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
                [15 ]Department of Statistics, European Organisation for Research and Treatment of Cancer, Brussels, Belgium
                [16 ]Currently with Bristol-Myers Squibb, Brussels, Belgium
                Article
                10.1001/jamaoncol.2018.5543
                6439568
                30543350
                41b3d87e-d410-487b-ac7b-9a045ec3a09a
                © 2018
                History

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