Comparison of upfront versus deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma receiving systemic therapy: a systematic review and meta-analysis

Background: This study aimed to conduct a pooled analysis to compare the outcomes of patients with metastatic renal cell carcinoma who received presurgical systemic therapy [(ST); including immunotherapy and/or targeted therapy] followed by cytoreductive nephrectomy (CN) [(deferred CN; (dCN)] with those who underwent upfront CN (uCN) followed by ST. Methods: The present study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A comprehensive search was conducted in PubMed, Embase, Web of Science, Scopus, and the Cochrane Library database to identify eligible comparative studies up to April 2023. To evaluate their relevance, pooled hazard ratio with 95% CIs were calculated. Results: A total of 3157 patients were included in nine studies. The dCN group was observed to be correlated with superior overall survival (OS) compared to the uCN group (hazard ratio =0.71, 95% CI 0.57–0.89, P=0.003). Moreover, the authors conducted subgroup analyses according to the type of ST, sample size, sex, age, and risk score, and observed similar outcomes for OS across most subgroups. Conclusions: The results of this study demonstrated that dCN may be associated with improved OS compared to uCN in patients with metastatic renal cell carcinoma receiving ST. However, no significant differences were found between the uCN and dCN groups in the immunotherapy-based combinations subgroup. Further research is needed to confirm these results.


Information sources
6 Specify all databases, registers, websites, organisations, reference lists and other sources searched or consulted to identify studies.
Specify the date when each source was last searched or consulted. Page4/Line68-69 Search strategy 7 Present the full search strategies for all databases, registers and websites, including any filters and limits used.Page4/Line68-75 Selection process 8 Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process. Page5/Line86-87

Data collection process
9 Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process.
Page5/Line87-92 Data items 10a List and define all outcomes for which data were sought.Specify whether all results that were compatible with each outcome domain in each study were sought (e.g. for all measures, time points, analyses), and if not, the methods used to decide which results to collect. Page5/Line86-92 10b List and define all other variables for which data were sought (e.g.participant and intervention characteristics, funding sources).Describe any assumptions made about any missing or unclear information. Page5/Line86-92

Study risk of bias assessment
11 Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process. Page5/Line93-97 Effect measures 12 Specify for each outcome the effect measure(s) (e.g.risk ratio, mean difference) used in the synthesis or presentation of results.Page5/Line100-101

Synthesis methods
13a Describe the processes used to decide which studies were eligible for each synthesis (e.g.tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item #5)). Page4/Line78-83 13b Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions.
Page5/Line 99-104 13c Describe any methods used to tabulate or visually display results of individual studies and syntheses.Page5/Line 99-104 13d Describe any methods used to synthesize results and provide a rationale for the choice(s).If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used.19 For all outcomes, present, for each study: (a) summary statistics for each group (where appropriate) and (b) an effect estimate and its precision (e.g.confidence/credible interval), ideally using structured tables or plots.

Table1 and Table2
Results of syntheses 20a For each synthesis, briefly summarise the characteristics and risk of bias among contributing studies.Page7/Line129-134 20b Present results of all statistical syntheses conducted.If meta-analysis was done, present for each the summary estimate and its precision (e.g.confidence/credible interval) and measures of statistical heterogeneity.If comparing groups, describe the direction of the effect.
methods used to assess certainty (or confidence) in the body of evidence for an outcome.Page5/Line93-97RESULTSStudy selection16a Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram.Page6/Line110-114, (Fig1)16b Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded.included study and present its characteristics.Page6/Line114-124Risk of bias in studies 18 Present assessments of risk of bias for each included study.Page7/Line129-134Results of individual studies

Page7
of all investigations of possible causes of heterogeneity among study results.Page7-9/Line135-170 20d Present results of all sensitivity analyses conducted to assess the robustness of the synthesized results.Page9/Line171-178 Reporting biases 21 Present assessments of risk of bias due to missing results (arising from reporting biases) for each synthesis assessed.Page9/Line179-183 Certainty of evidence 22 Present assessments of certainty (or confidence) in the body of evidence for each outcome assessed.Page7-9/Line135-170 DISCUSSION Discussion 23a Provide a general interpretation of the results in the context of other evidence.Page9-14/Line184-280 23b Discuss any limitations of the evidence included in the review.Page13-14/Line269-280 23c Discuss any limitations of the review processes used.Page13-14/Line269-271 23d Discuss implications of the results for practice, policy, and future research.