The role of cytoreductive nephrectomy (CN) in the immune checkpoint inhibitor (ICI) era of metastatic renal cell carcinoma (mRCC): A systematic review and individual patient data (IPD) meta-analysis of 2319 patients.

Authors

null

Dimitrios Makrakis

Department of Medicine, NYC Health + Hospitals/Jacobi, Albert Einstein College of Medicine, Bronx, NY

Dimitrios Makrakis , Pavlos Msaouel , Jose A. Karam , Stepan M. Esagian

Organizations

Department of Medicine, NYC Health + Hospitals/Jacobi, Albert Einstein College of Medicine, Bronx, NY, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX

Research Funding

No funding sources reported

Background: The combination of CN and systemic therapy has been established as one of the mainstay treatments for mRCC during the targeted therapy era. However, the role of CN in the ICI era remains unclear. Methods: We performed a systematic search of the MEDLINE, EMBASE, and Web of Science databases until August 26th, 2023, for studies comparing the combination of CN + ICI vs. ICI alone in mRCC. Using published Kaplan-Meier overall survival (OS) curves, we reconstructed IPD and then performed one-stage and two-stage meta-analyses with both parametric and non-parametric effect estimates. To account for immortal time bias, we performed 6-month and 12-month landmark analyses. We also performed a subgroup analysis according to ICI line of treatment. The risk of bias was assessed using the ROBINS-I tool. Results: We identified eight retrospective cohort studies fulfilling our inclusion criteria. Only two out of eight studies adjusted for immortal time bias and none of them adequately adjusted for all predetermined confounding factors. A total of 2319 (1264 CN + ICI and 1055 ICI only) patients were included in our analysis. Patients in CN + ICI group were younger (median age 58.2 vs. 62.8), had lower proportions of non-clear cell histology (8.8% vs. 15.2%), ≥2 metastatic sites (60.0% vs. 68.5%), liver metastases (9.0% vs. 21.9%), and poor IMDC risk score (21.7% vs. 43.9%), but had higher proportions of sarcomatoid histology (15.6% vs. 10.6%) and ≥2nd line treatment (38.1% vs. 17.1%). The combination of CN + ICI was associated with superior OS in the one stage (HR: 0.45, 95% CI 0.38–0.52), 6-month landmark (HR: 0.45, 95% CI 0.37–0.54), 12-month landmark (HR: 0.50, 95% CI 0.31–0.50) and two-stage (HR: 0.38, 95% CI 0.29–0.49) meta-analyses. Similarly, the combination of CN + ICI was associated with superior OS in the subgroup of patients receiving first-line ICI (HR 0.39, 95% CI: 0.30–0.48). Conclusions: The combination of CN + ICI for mRCC may be associated with superior OS compared to ICI alone, but currently available data are subject to selection bias. More studies, including well-designed randomized controlled trials, are needed to determine the role of CN in the ICI era.

AnalysisOutcome MeasureValue95% CIp-value
One-stage meta-analysisHR0.450.38–0.52<0.001
One-stage meta-analysis (6-month landmark)HR0.450.37–0.54<0.001
One-stage meta-analysis (12-month landmark)HR0.500.31–0.50<0.001
Two-stage meta-analysisHR0.380.29–0.49<0.001
1-year life expectancy differenceMonths1.050.74–1.35<0.001
1-year life expectancy ratioRatio1.111.07–1.14<0.001
3-year life expectancy differenceMonths7.125.75–8.48<0.001
3-year life expectancy ratioRatio1.361.28–1.44<0.001
First-line ICI only (6-month landmark)HR0.390.30–0.48<0.001

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Abstract Details

Meeting

2024 ASCO Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session C: Renal Cell Cancer; Adrenal, Penile, and Testicular Cancers

Track

Renal Cell Cancer,Adrenal Cancer,Penile Cancer,Testicular Cancer

Sub Track

Therapeutics

Citation

J Clin Oncol 42, 2024 (suppl 4; abstr 425)

DOI

10.1200/JCO.2024.42.4_suppl.425

Abstract #

425

Poster Bd #

H7

Abstract Disclosures

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