Alessandro Antonelli1, Andrea Minervini2, Marco Sandri3, Roberto Bertini4, Riccardo Bertolo5, Marco Carini2, Maria Furlan6, Alessandro Larcher4, Guglielmo Mantica7, Andrea Mari2, Francesco Montorsi4, Carlotta Palumbo6, Francesco Porpiglia5, Paola Romagnani8, Claudio Simeone6, Carlo Terrone7, Umberto Capitanio4. 1. Department of Urology, Spedali Civili Hospital, University of Brescia, Brescia, Italy. Electronic address: alessandro_antonelli@me.com. 2. Department of Urology, Careggi Hospital, University of Florence, Florence, Italy. 3. Data Methods and Systems Statistical Laboratory, University of Brescia, Brescia, Italy. 4. Division of Experimental Oncology, Department of Urology, URI-Urological Research Institute, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy. 5. Department of Urology, San Luigi Gonzaga Hospital, School of Medicine, Orbassano, Turin, Italy. 6. Department of Urology, Spedali Civili Hospital, University of Brescia, Brescia, Italy. 7. Department of Urology, IRCCS San Martino Hospital, University of Genoa, Genoa, Italy. 8. Department of Biomedical Experimental and Clinical Science "Mario Serio", University of Florence, Florence, Italy.
Abstract
BACKGROUND: The hypothesis that renal function could influence oncological outcomes is supported by anecdotal literature. OBJECTIVE: To determine whether estimated glomerular filtration rate (eGFR) is related to cancer-specific mortality (CSM) in patients who had undergone surgery for renal cell carcinoma (RCC). DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of 3457 patients who underwent radical (39%) or partial nephrectomy (61%) for cT1-2 RCC between 1990 and 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The eGFR was calculated by the Chronic Kidney Disease Epidemiology Collaboration equation. CSM was analyzed in a multivariable competing-risk framework, estimating the subdistribution hazard ratio (SHR) accounting for deaths from other causes. The relationship between eGFR and CSM was investigated from multiple statistical approaches-extended Cox regression with eGFR incorporated as a time-dependent covariate, landmark analysis, and joint modeling. Other predictors were selected by competing-risk random forest method and backward elimination. RESULTS AND LIMITATIONS: The relationship between eGFR and CSM was graphically described by a linear spline, i.e. a continuous piecewise linear function with two lines joined by a knot. For eGFR treated as a time-dependent covariate, the knot was located at 65ml/min; at landmark analysis with eGFR at the baseline, 12 mo, and last functional follow-up, the knots were 85, 60, and 65ml/min, respectively. In multivariable competing-risk analysis, CSM was associated with eGFR only for values of eGFR below these cutoffs, with SHRs for every 10ml/min of reduction in eGFR of 1.25 (p=0.003), 1.16 (p=0.028), 1.44 (p=0.02), and 1.16 (p=0.042), corresponding to time-dependent eGFR, and eGFR at baseline, 12 mo, and last functional follow-up, respectively. Joint modeling confirmed these results. A retrospective design with inherent biases in data collection represents a limitation. CONCLUSIONS: In patients undergoing surgery for RCC, renal function should be preserved in order to improve cancer-related survival. PATIENT SUMMARY: The relationship between renal function and probability of dying due to renal cancer is complex. The present study found a correlation between glomerular filtration rate and cancer specific mortality that could reconsider the oncological role of renal function in patients undergoing surgery for renal cancer.
BACKGROUND: The hypothesis that renal function could influence oncological outcomes is supported by anecdotal literature. OBJECTIVE: To determine whether estimated glomerular filtration rate (eGFR) is related to cancer-specific mortality (CSM) in patients who had undergone surgery for renal cell carcinoma (RCC). DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of 3457 patients who underwent radical (39%) or partial nephrectomy (61%) for cT1-2 RCC between 1990 and 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The eGFR was calculated by the Chronic Kidney Disease Epidemiology Collaboration equation. CSM was analyzed in a multivariable competing-risk framework, estimating the subdistribution hazard ratio (SHR) accounting for deaths from other causes. The relationship between eGFR and CSM was investigated from multiple statistical approaches-extended Cox regression with eGFR incorporated as a time-dependent covariate, landmark analysis, and joint modeling. Other predictors were selected by competing-risk random forest method and backward elimination. RESULTS AND LIMITATIONS: The relationship between eGFR and CSM was graphically described by a linear spline, i.e. a continuous piecewise linear function with two lines joined by a knot. For eGFR treated as a time-dependent covariate, the knot was located at 65ml/min; at landmark analysis with eGFR at the baseline, 12 mo, and last functional follow-up, the knots were 85, 60, and 65ml/min, respectively. In multivariable competing-risk analysis, CSM was associated with eGFR only for values of eGFR below these cutoffs, with SHRs for every 10ml/min of reduction in eGFR of 1.25 (p=0.003), 1.16 (p=0.028), 1.44 (p=0.02), and 1.16 (p=0.042), corresponding to time-dependent eGFR, and eGFR at baseline, 12 mo, and last functional follow-up, respectively. Joint modeling confirmed these results. A retrospective design with inherent biases in data collection represents a limitation. CONCLUSIONS: In patients undergoing surgery for RCC, renal function should be preserved in order to improve cancer-related survival. PATIENT SUMMARY: The relationship between renal function and probability of dying due to renal cancer is complex. The present study found a correlation between glomerular filtration rate and cancer specific mortality that could reconsider the oncological role of renal function in patients undergoing surgery for renal cancer.
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