Renzo G DiNatale1, Wanling Xie2, Maria F Becerra3, Andrew W Silagy4, Kyrollis Attalla5, Alejandro Sanchez5, Roy Mano5, Julian Marcon6, Kyle A Blum7, Nicole E Benfante5, Martin H Voss8, Robert J Motzer8, Jonathan Coleman5, Toni K Choueiri9, Ed Reznik10, Paul Russo5, Daniel Y C Heng11, A Ari Hakimi12. 1. Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Computational Oncology Service, Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 2. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA. 3. Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Urology, University of Miami, Miller School of Medicine, Miami, FL, USA. 4. Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Surgery, University of Melbourne, Austin Hospital, Melbourne, Australia. 5. Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 6. Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Urology, University Hospital of Munich, Munich, Germany. 7. Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 8. Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 9. Department of Medicine, Dana-Farber Cancer Institute, Boston, MA, USA. 10. Computational Oncology Service, Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 11. Department of Medicine, Tom Baker Cancer Center, Calgary, AB, Canada. 12. Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: hakimia@mskcc.org.
Abstract
BACKGROUND: One of the main challenges in the management of renal cell carcinoma (RCC) is risk-stratifying patients who present with metastatic disease. Tumor size is an important predictor of survival in the localized setting; however, this feature has not been explored fully in patients presenting with M1 RCC. OBJECTIVE: To assess the impact of tumor size on survival in patients with metastatic RCC who underwent cytoreductive nephrectomy (CN). DESIGN, SETTING, AND PARTICIPANTS: We queried the Memorial Sloan Kettering (MSK) nephrectomy database for patients who presented with M1 disease and underwent CN between 1989 and 2016 (n=304). Primary tumor size was obtained from pathology reports. Data from the International Metastatic Database Consortium (IMDC) were used for validation purposes (n=778). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) estimates were computed using the Kaplan-Meier method. Cox regressions were used to test the association between tumor size and OS in univariate and multivariable analyses. Tumors ≤4cm were compared with larger masses. Secondary analyses were performed to assess the robustness of these findings. RESULTS AND LIMITATIONS: Clear cell tumors ≤4cm were significantly associated with improved OS in both the MSK (hazard ratio [HR]: 0.35, 0.17-0.72, p= 0.004) and IMDC (HR 0.54, 0.36-0.83, p= 0.004) cohorts. The association was observed even after adjusting for known prognostic factors (HR 0.40, 0.14-1.14, p= 0.09 and HR: 0.54, 0.33-0.90, p= 0.02 in the MSK and IMDC cohorts, respectively). Limitations of this study include the absence of patients who were considered poor surgical candidates as well as potential selection bias. CONCLUSIONS: The primary tumor size ≤4cm was independently associated with improved OS in patients with metastatic clear cell RCC who underwent CN. Additionally, the association between primary size and survival was found to be nonlinear. These findings suggest that there is a group of small metastatic RCCs that can convey a better overall prognosis. The potential role of primary tumor size when risk stratifying patients with M1 RCC should be explored further to determine its utility during clinical decision making. PATIENT SUMMARY: We evaluated the impact of small tumor size on prognosis in patients with metastatic kidney cancer who undergo removal of the primary tumor. Very small masses (≤4cm) were associated with better prognosis in patients with clear cell tumors.
BACKGROUND: One of the main challenges in the management of renal cell carcinoma (RCC) is risk-stratifying patients who present with metastatic disease. Tumor size is an important predictor of survival in the localized setting; however, this feature has not been explored fully in patients presenting with M1 RCC. OBJECTIVE: To assess the impact of tumor size on survival in patients with metastatic RCC who underwent cytoreductive nephrectomy (CN). DESIGN, SETTING, AND PARTICIPANTS: We queried the Memorial Sloan Kettering (MSK) nephrectomy database for patients who presented with M1 disease and underwent CN between 1989 and 2016 (n=304). Primary tumor size was obtained from pathology reports. Data from the International Metastatic Database Consortium (IMDC) were used for validation purposes (n=778). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) estimates were computed using the Kaplan-Meier method. Cox regressions were used to test the association between tumor size and OS in univariate and multivariable analyses. Tumors ≤4cm were compared with larger masses. Secondary analyses were performed to assess the robustness of these findings. RESULTS AND LIMITATIONS: Clear cell tumors ≤4cm were significantly associated with improved OS in both the MSK (hazard ratio [HR]: 0.35, 0.17-0.72, p= 0.004) and IMDC (HR 0.54, 0.36-0.83, p= 0.004) cohorts. The association was observed even after adjusting for known prognostic factors (HR 0.40, 0.14-1.14, p= 0.09 and HR: 0.54, 0.33-0.90, p= 0.02 in the MSK and IMDC cohorts, respectively). Limitations of this study include the absence of patients who were considered poor surgical candidates as well as potential selection bias. CONCLUSIONS: The primary tumor size ≤4cm was independently associated with improved OS in patients with metastatic clear cell RCC who underwent CN. Additionally, the association between primary size and survival was found to be nonlinear. These findings suggest that there is a group of small metastatic RCCs that can convey a better overall prognosis. The potential role of primary tumor size when risk stratifying patients with M1 RCC should be explored further to determine its utility during clinical decision making. PATIENT SUMMARY: We evaluated the impact of small tumor size on prognosis in patients with metastatic kidney cancer who undergo removal of the primary tumor. Very small masses (≤4cm) were associated with better prognosis in patients with clear cell tumors.
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