Lorenzo Marconi1, Roderick de Bruijn2, Erik van Werkhoven2, Christian Beisland3,4, Kate Fife5, Axel Heidenreich6, Anil Kapoor7, Jose Karam8, Caroline Kauffmann6, Tobias Klatte9, Boerje Ljungberg10, Surena Matin8, Daniel Sjoberg11, Michael Staehler12, Grant D Stewart5,13,14, Simon Tanguay15, Robert Uzzo16, Sarah Welsh5, Lori Wood17,18, Chris Wood8, Axel Bex19. 1. Department of Urology, Coimbra University Hospital, Coimbra, Portugal. 2. Division of Surgical Oncology, Department of Urology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. 3. Department of Urology, Haukeland University Hospital, Bergen, Norway. 4. Department of Clinical Medicine, University of Bergen, Bergen, Norway. 5. Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, University of Cambridge, Cambridge, UK. 6. Department of Urology, University Hospital Cologne, Cologne, Germany. 7. Department of Surgery, McMaster University, Hamilton, Canada. 8. The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 9. Department of Urology, Medical University of Vienna, Vienna, Austria. 10. Department of Urology, Umeå University, Umea, Sweden. 11. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 12. University Hospital Munich-Grosshadern, Ludwig Maximilian University, Munich, Germany. 13. Department of Surgery, University of Cambridge, Cambridge Biomedical Campus, Hill's Road, Cambridge, UK. 14. Department of Surgery, University of Edinburgh, Edinburgh, UK. 15. Department of Urology, McGill University, Montreal, Canada. 16. Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA, USA. 17. Queen Elizabeth II Health Science Centre, Halifax, Canada. 18. The Kidney Cancer Research Network of Canada, Hamilton, ON, Canada. 19. Division of Surgical Oncology, Department of Urology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. a.bex@nki.nl.
Abstract
INTRODUCTION: Recent trials have emphasized the importance of a precise patient selection for cytoreductive nephrectomy (CN). In 2013, a nomogram was developed for pre- and postoperative prediction of the probability of death (PoD) after CN in patients with metastatic renal cell carcinoma. To date, the single-institutional nomogram which included mostly patients from the cytokine era has not been externally validated. Our objective is to validate the predictive model in contemporary patients in the targeted therapy era. METHODS: Multi-institutional European and North American data from patients who underwent CN between 2006 and 2013 were used for external validation. Variables evaluated included preoperative serum albumin and lactate dehydrogenase levels, intraoperative blood transfusions (yes/no) and postoperative pathologic stage (primary tumour and nodes). In addition, patient characteristics and MSKCC risk factors were collected. Using the original calibration indices and quantiles of the distribution of predictions, Kaplan-Meier estimates and calibration plots of observed versus predicted PoD were calculated. For the preoperative model a decision curve analysis (DCA) was performed. RESULTS: Of 1108 patients [median OS of 27 months (95% CI 24.6-29.4)], 536 and 469 patients had full data for the validation of the pre- and postoperative models, respectively. The AUC for the pre- and postoperative model was 0.68 (95% CI 0.62-0.74) and 0.73 (95% CI 0.68-0.78), respectively. In the DCA the preoperative model performs well within threshold survival probabilities of 20-50%. Most important limitation was the retrospective collection of this external validation dataset. CONCLUSIONS: In this external validation, the pre- and postoperative nomograms predicting PoD following CN were well calibrated. Although performance of the preoperative nomogram was lower than in the internal validation, it retains the ability to predict early death after CN.
INTRODUCTION: Recent trials have emphasized the importance of a precise patient selection for cytoreductive nephrectomy (CN). In 2013, a nomogram was developed for pre- and postoperative prediction of the probability of death (PoD) after CN in patients with metastatic renal cell carcinoma. To date, the single-institutional nomogram which included mostly patients from the cytokine era has not been externally validated. Our objective is to validate the predictive model in contemporary patients in the targeted therapy era. METHODS: Multi-institutional European and North American data from patients who underwent CN between 2006 and 2013 were used for external validation. Variables evaluated included preoperative serum albumin and lactate dehydrogenase levels, intraoperative blood transfusions (yes/no) and postoperative pathologic stage (primary tumour and nodes). In addition, patient characteristics and MSKCC risk factors were collected. Using the original calibration indices and quantiles of the distribution of predictions, Kaplan-Meier estimates and calibration plots of observed versus predicted PoD were calculated. For the preoperative model a decision curve analysis (DCA) was performed. RESULTS: Of 1108 patients [median OS of 27 months (95% CI 24.6-29.4)], 536 and 469 patients had full data for the validation of the pre- and postoperative models, respectively. The AUC for the pre- and postoperative model was 0.68 (95% CI 0.62-0.74) and 0.73 (95% CI 0.68-0.78), respectively. In the DCA the preoperative model performs well within threshold survival probabilities of 20-50%. Most important limitation was the retrospective collection of this external validation dataset. CONCLUSIONS: In this external validation, the pre- and postoperative nomograms predicting PoD following CN were well calibrated. Although performance of the preoperative nomogram was lower than in the internal validation, it retains the ability to predict early death after CN.
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