Role of cytoreductive nephrectomy in the targeted therapy era: A systematic review and meta-analysis

Abstract

PurposeTo determine the effectiveness and harm of cytoreductive nephrectomy versus no intervention in patients with metastatic renal carcinoma who undergo targeted therapy to improve overall survival.Materials and MethodsA search strategy was conducted in the MEDLINE, CENTRAL, Embase, HTA, DARE, NHS, and LILACS databases. Searches were also conducted for unpublished literature through references from relevant articles identified through the search, conferences, thesis databases, OpenGrey, Google Scholar, and clinicaltrials.gov, among others. Studies were included without language restrictions. The risk of bias assessment was made by using a modified Cochrane Collaboration tool. A meta-analysis of fixed effects was conducted. The expected outcomes were overall survival, quality of life, adverse effects, mortality, and progression- free survival. The measure of the effect was the hazard ratio (HR) with a 95% confidence interval (CI). The planned comparison was cytoreductive nephrectomy versus no intervention.ResultsA total of 22,507 patients were found among seven studies. Seven studies were included in the qualitative analysis (eight publications) and five in the quantitative analysis for overall survival. One study reported progression-free survival and one reported targeted therapy toxicities. A low risk of bias was shown for most of the study items. The HR for overall survival was 0.58 (95% CI, 0.50 to 0.65) favoring cytoreductive nephrectomy compared with no intervention.ConclusionsCytoreductive nephrectomy is effective for improving overall survival in patients with metastatic renal carcinoma who undergo targeted therapy compared with no intervention.

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

“…Although several meta-analyses have attempted to address this topic in the past, limitations in their methodology have precluded any definitive conclusions [ 48 , 49 , 50 , 51 , 52 ]. In some cases, multiple overlapping populations were included [ 48 , 49 , 50 , 51 , 52 ] and eligible studies were omitted [ 48 , 50 , 51 , 52 ] resulting in significant bias due to the disproportionate representation of certain patient populations.…”

“…Although several meta-analyses have attempted to address this topic in the past, limitations in their methodology have precluded any definitive conclusions [ 48 , 49 , 50 , 51 , 52 ]. In some cases, multiple overlapping populations were included [ 48 , 49 , 50 , 51 , 52 ] and eligible studies were omitted [ 48 , 50 , 51 , 52 ] resulting in significant bias due to the disproportionate representation of certain patient populations. An additional limitation of studies analyzing databases (e.g., the Surveillance Epidemiology and End-Results database and the National Cancer Data Base) included in the previous meta-analyses [ 48 , 50 , 52 ] is the use of surrogate coding markers, such as the year of diagnosis or the receipt of systemic therapy, to identify patients receiving targeted therapy [ 53 , 54 ].…”

Do Metastatic Kidney Cancer Patients Benefit From Cytoreductive Nephrectomy? A Real-World Retrospective Study From the SEER Database

“…Several meta-analysis and retrospective studies supported CN combined with target therapy instead of target therapy alone ( 7 , 8 ). However, a recent randomized CARMENA study opposed the above review and demonstrated that sunitinib alone was not inferior to sunitinib plus nephrectomy for the primary end point of OS.…”

Cytoreductive Nephrectomy and Overall Survival of Patients with Metastatic Renal Cell Carcinoma Treated with Targeted Therapy—Data from the National Renis Registry

“…CARMENA, the only prospective phase III trial studying CN in the context of TT, showed that the omission of CN and upfront initiation of sunitinib therapy in patients with synchronous mRCC is non-inferior compared to CN followed by sunitinib [ 6 ]. However, the CARMENA trial has been criticized and the conclusions have not been universally accepted [ 7 ], partly because of the contradiction with large retrospective studies [ 8 , 9 , 10 , 11 ] and meta-analyses [ 12 , 13 , 14 ]. The CARMENA study suffered from slow accrual that led to premature closure after the second interim analysis.…”