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Long-Term Survival Outcomes of Cytoreductive Nephrectomy Combined with Targeted Therapy for Metastatic Renal Cell Carcinoma: A Systematic Review and Individual Patient Data Meta-Analysis.

ABSTRACT: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) remains controversial during the targeted therapy era. To reconcile the current literature, we analyzed the reported survival data at the individual patient level and compared the long-term survival outcomes of CN combined with targeted therapy vs. targeted therapy alone in patients with mRCC. We performed a systematic review of the literature using the MEDLINE, Scopus, and Cochrane Library databases (end-of-search date: 21 July 2020). We recuperated individual patient data from the Kaplan-Meier curves for overall (OS), progression-free (PFS), and cancer-specific survival (CSS) from each study. We subsequently performed one-stage frequentist and Bayesian random-effects meta-analyses using both Cox proportional hazards and restricted mean survival time (RMST) models. Two-stage random-effects meta-analyses were also performed as sensitivity analyses. A subgroup analysis was also performed to determine the effect of CN timing. Fifteen studies fulfilling our inclusion criteria were identified, including fourteen retrospective cohort studies and one randomized controlled trial. In the one-stage frequentist meta-analysis, the CN group had superior OS (hazard ratio [HR]: 0.58, 95% confidence interval [CI]: 0.54-0.62, p < 0.0001) and CSS (HR: 0.63, 95% CI: 0.53-0.75, p < 0.0001). No meaningful clinical difference was observed in PFS (HR: 0.90, 95% CI: 0.80-1.02, p = 0.09). One-stage Bayesian meta-analysis also revealed superior OS (HR: 0.59, 95% credibility interval [CrI]: 0.55-0.63) and CSS (HR: 0.63, 95% CrI: 0.53-0.75) in the CN group, while no meaningful clinical difference was detected in PFS (HR: 0.91, 95% CrI: 0.80-1.02). Similar results were obtained with the RMST models. The OS benefit was also noted in the two-stage meta-analyses models, and in the subgroup of patients who received upfront CN. The combination of CN and targeted therapy for mRCC may lead to superior long-term survival outcomes compared to targeted therapy alone. Careful patient selection based on prognostic factors is required to optimize outcomes.

SUBMITTER: Esagian SM

PROVIDER: S-EPMC7915816 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe metastatic renal cell carcinoma (mRCC) patients treated with upfront cytoreductive nephrectomy combined with α-interferon yields additional overall survival (OS) benefits. It is unclear whether mRCC patients treated with vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) will benefit from such cytoreductive nephrectomy either. The aim of the study was to identify variables for selection of patients who would benefit from upfront cytoreductive nephrectomy for mRCC treated with VEGFR-TKI.MethodsClinical data on 74 patients enrolled in 5 clinical trials conducted in Cancer Hospital (Institute), Chinese Academy of Medical Sciences from January 2006 to January 2014 were reviewed retrospectively. The survival analysis was performed by the Kaplan-Meier method. Comparisons between patient groups were performed by Chi-square test. A Cox regression model was adopted for analysis of multiple factors affecting survival, with a significance level of α = 0.05.ResultsFifty-one patients underwent cytoreductive nephrectomy followed by targeted therapy (cytoreductive nephrectomy group) and 23 patients were treated with targeted therapy alone (noncytoreductive nephrectomy group). The median OS was 32.2 months and 23.0 months in cytoreductive nephrectomy and noncytoreductive nephrectomy groups, respectively (P = 0.041). Age ≤45 years (P = 0.002), a low or high body mass index (BMI <19 or >30 kg/m2) (P = 0.008), a serum lactate dehydrogenase (LDH) concentration >1.5 × upper limit of normal (P = 0.025), a serum calcium concentration >10 mg/ml (P = 0.034), and 3 or more metastatic sites (P = 0.023) were independent preoperative risk factors for survival. The patients only with 0-2 risk factors benefited from upfront cytoreductive nephrectomy in terms of OS when compared with the patients treated with targeted therapy alone (40.0 months vs. 23.2 months, P = 0.042), while those with more than 2 risk factors did not.ConclusionsFive risk factors (age, BMI, LDH, serum calcium, and number of metastatic sites) seemed to be helpful for selecting patients who would benefit from undergoing upfront cytoreductive nephrectomy.

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Long-Term Survival Outcomes of Cytoreductive Nephrectomy Combined with Targeted Therapy for Metastatic Renal Cell Carcinoma: A Systematic Review and Individual Patient Data Meta-Analysis.

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