Aim: To compare the efficacy of first-line immune checkpoint inhibitor (ICI)-based combinations in metastatic renal cell carcinoma (mRCC) patients stratified by chronological age. Methods: According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, hazard ratios for overall survival (OS) from randomized controlled trials were synthesized. Results: Five RCTs were eligible for meta-analyses. ICI-based combinations significantly improved OS compared with sunitinib alone, both in younger (<65 years) and older (≥65 years) patients, whereas the OS benefit was significantly better in younger patients (p = 0.007). ICI-based combinations did not improve OS in patients aged ≥75 years. Treatment rankings showed age-related differential recommendations regarding improved OS. Conclusion: OS benefit from first-line ICI-based combinations was significantly greater in younger patients. Age-related differences could help enrich shared decision-making.

Scientists have found a special way to treat a type of cancer called metastatic renal cell carcinoma. They use a combination of medicines that help the body's immune system fight cancer. These treatments are very effective and recommended as the first choice for patients with this type cancer. However, as people get older, their immune systems may not work as well. Studies looking at how these treatments work in different age groups, and it was discovered that these treatments improved the chances of survival for all patients, no matter their age. However, they also noticed that younger patients got even more benefits from the treatments. Because of these discoveries, doctors can now make better decisions about which treatment to use for patients with this type of cancer, depending on patient age.

Cancer Prognostics and Health Outcomes Unit Division of Urology University of Montreal Health Center Montreal QC H2X 0A9 Canada

Clinic of Urology and Urological Oncology Jagiellonian University Krakow 30 688 Poland

Department of Urology 2nd Faculty of Medicine Charles University Prague 15006 Czech Republic

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna 1090 Austria

Department of Urology King Fahad Specialist Hospital Dammam 32253 Saudi Arabia

Department of Urology La Croix Du Sud Hospital Quint Fonsegrives 31130 France

Department of Urology Medical University of Silesia Zabrze 41 800 Poland

Department of Urology Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama 700 8530 Japan

Department of Urology The Jikei University School of Medicine Tokyo 105 8461 Japan

Department of Urology University Medical Center Hamburg Eppendorf Hamburg 20251 Germany

Department of Urology University of Texas Southwestern Medical Center Dallas TX 75390 USA

Department of Urology Weill Cornell Medical College NY 10021 USA

Division of Urology Department of Special Surgery The University of Jordan Amman 19328 Jordan

Institute for Urology and Reproductive Health Sechenov University Moscow 119435 Russia

Karl Landsteiner Institute of Urology and Andrology Vienna 1090 Austria

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