Roderick de Bruijn1, Akhila Wimalasingham2, Bernadett Szabados2, Grant D Stewart3, Sarah J Welsh4, Teele Kuusk5, Christian Blank6, John Haanen6, Tobias Klatte7, Michael Staehler8, Thomas Powles2, Axel Bex9. 1. Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands. 2. Barts Cancer Institute, Queen Mary University of London, London, UK. 3. Department of Urology, University of Edinburgh, Edinburgh, UK. 4. Department of Urology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. 5. Specialist Centre for Kidney Cancer, Royal Free London NHS Foundation Trust, UCL Division of Surgical and Interventional Science, London, UK. 6. Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. 7. Department of Urology, Royal Bournemouth Hospital, Bournemouth, UK; Department of Urology, Medical University of Vienna, Vienna, Austria. 8. Department of Urology, Ludwig Maximilian University, Munich, Germany. 9. Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands; Specialist Centre for Kidney Cancer, Royal Free London NHS Foundation Trust, UCL Division of Surgical and Interventional Science, London, UK. Electronic address: a.bex@ucl.ac.uk.
Abstract
BACKGROUND: Cancer du Rein Métastatique Nephrectomie et Antiangiogéniques (CARMENA) concluded that sunitinib alone is not inferior to cytoreductive nephrectomy (CN) followed by vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) in patients with metastatic renal cell carcinoma. It remains uncertain whether deferred CN is beneficial in this setting. OBJECTIVE: The aim of this study was to compare outcome in patients treated with presurgical VEGFR-TKI followed by CN (deferred CN) with that in patients receiving CN followed by VEGFR-TKI (upfront CN). DESIGN, SETTING, AND PARTICIPANTS: Pooled data from prospective trials in which a strategy of deferred CN in the absence of disease progression was investigated were compared with a retrospective dataset of upfront CN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) in the Memorial Sloan-Kettering Cancer Center (MSKCC) intermediate-risk group. RESULTS AND LIMITATIONS: Patients were treated between 2006 and 2016. In the MSKCC intermediate-risk group, 144 patients with a strategy of deferred CN after systemic therapy were compared with 131 patients treated with upfront CN. OS in the deferred cohort was 33.0 mo (95% confidence interval [CI] 25.0-51.0) compared with 22.8 mo (95% CI 17.9-30.6) after upfront CN (hazard ratio 0.72 [95% CI 0.52-0.996], p = 0.047). This study is limited by retrospective comparison of data, subgroup analysis, and a lack of intention-to-treat data for the upfront CN cohort. CONCLUSIONS: In MSKCC intermediate-risk patients, a strategy of deferred CN in the absence of progression yields OS, which compares favourably with upfront CN and published trial data from CARMENA. This warrants a formal individual patient data analysis of CARMENA, SURTIME, and single-arm prospective studies to define the role and timing of deferred CN in intermediate-risk patients. PATIENT SUMMARY: In this study, we report outcomes in patients with metastatic renal cell cancer treated with targeted therapy followed by nephrectomy, which compared favourably with nephrectomy followed by targeted therapy and results from published studies.
BACKGROUND: Cancer du Rein Métastatique Nephrectomie et Antiangiogéniques (CARMENA) concluded that sunitinib alone is not inferior to cytoreductive nephrectomy (CN) followed by vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) in patients with metastatic renal cell carcinoma. It remains uncertain whether deferred CN is beneficial in this setting. OBJECTIVE: The aim of this study was to compare outcome in patients treated with presurgical VEGFR-TKI followed by CN (deferred CN) with that in patients receiving CN followed by VEGFR-TKI (upfront CN). DESIGN, SETTING, AND PARTICIPANTS: Pooled data from prospective trials in which a strategy of deferred CN in the absence of disease progression was investigated were compared with a retrospective dataset of upfront CN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) in the Memorial Sloan-Kettering Cancer Center (MSKCC) intermediate-risk group. RESULTS AND LIMITATIONS: Patients were treated between 2006 and 2016. In the MSKCC intermediate-risk group, 144 patients with a strategy of deferred CN after systemic therapy were compared with 131 patients treated with upfront CN. OS in the deferred cohort was 33.0 mo (95% confidence interval [CI] 25.0-51.0) compared with 22.8 mo (95% CI 17.9-30.6) after upfront CN (hazard ratio 0.72 [95% CI 0.52-0.996], p = 0.047). This study is limited by retrospective comparison of data, subgroup analysis, and a lack of intention-to-treat data for the upfront CN cohort. CONCLUSIONS: In MSKCC intermediate-risk patients, a strategy of deferred CN in the absence of progression yields OS, which compares favourably with upfront CN and published trial data from CARMENA. This warrants a formal individual patient data analysis of CARMENA, SURTIME, and single-arm prospective studies to define the role and timing of deferred CN in intermediate-risk patients. PATIENT SUMMARY: In this study, we report outcomes in patients with metastatic renal cell cancer treated with targeted therapy followed by nephrectomy, which compared favourably with nephrectomy followed by targeted therapy and results from published studies.
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