Comparison of IO-IO and IO-TKI Treatment Outcomes in Metastatic Renal Cell Carcinoma - Influence of Metastatic Site Count

Q: What treatment strategies were compared in the study?

The study compared dual immune checkpoint blockade (IO-IO) with a combination of immunotherapy and tyrosine kinase inhibitors (IO-TKI) for metastatic renal cell carcinoma.

Q: How was the number of metastatic organs evaluated for its prognostic impact?

The analysis focused on metastatic organ count and assessed its relationship with survival using multivariable Cox proportional hazards models and treatment-by-metastatic-organ interaction terms.

Q: What was the main finding regarding efficacy differences between IO-TKI and IO-IO?

The number of metastatic organs affected outcomes in the IO-TKI group but showed no effect on progression-free survival in the IO-IO group.

Sep 28, 2026

Uploaded by mieayamfan

Background/Aim: The therapeutic efficacy of Immuno-Oncology combination therapy based on the number of metastatic organs in renal cancer has yet to be examined. Therefore, this retrospective work compared dual immune checkpoint blockade (IO-IO) versus immunotherapy plus tyrosine kinase inhibitors (IO-TKI) in metastatic renal cell carcinoma, emphasizing how metastatic organ count influences outcomes. Patients and Methods: 147 patients receiving systemic therapy (Aug 2015–Jul 2023) were analyzed with multivariable Cox models and interaction terms. Results identified key predictors of progression-free survival and showed divergent effects between treatment groups.

LanguageEnglish

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Abstract

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Patients and Methods

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doi: 10.21873/cdp.10513 Comparison of IO-IO and IO-TKI Treatment Outcomesin Metastatic Renal Cell Carcinoma: Influence of Metastatic Site Count HIROSHI KIKUCHI1, TAKAHIRO OSAWA1, SEI NAITO2, KAZUYUKI NUMAKURA3, OJIRO TOKAIRIN1, YUKI TAKAI2, YUYA SEKINE3, HARUKA MIYATA1, RYUJI MATSUMOTO1, TAKASHIGE ABE1, YOICHI ITO4, TOMONORI HABUCHI3, NORIHIKOTSUCHIYA2 and NOBUO SHINOHARA1 1 Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; 2 Department of Urology, Yamagata University Faculty of Medicine, Yamagata, Japan; 3 Department of Urology, Akita University Graduate School of Medicine, Akita, Japan; 4Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Sapporo, Japan Abstract Background/Aim: The therapeutic efficacy of Immuno-Oncology combination therapy based on the number of metastatic organs in renal cancer has yet to be examined. Therefore, we herein compared the efficacy of dual immune checkpoint blockade (IO-IO) and combination of immunotherapy with tyrosine kinase inhibitors (IO-TKI) strategies in metastatic renal cell carcinoma (mRCC), with a focus on how the number of metastatic organs affects clinical outcomes. Patients and Methods: This retrospective study included 147 patients with mRCC treated with systemic therapies between August 2015 and July 2023. A multivariable Cox proportional hazards model was used to examine the relationships between clinical parameters and survival. To examine whether the effects of the number of metastatic organs on survival varied between treatment regimens, interaction terms were evaluated. Results: In the multivariate Cox regression analysis, IMDC poor risk [hazard ratio (HR)=1.95; 95% confidence interval (CI)=1.19-3.18] and the presence of three or more metastatic organs in the IO-TKI group (HR=3.72; 95% CI=1.35- 10.23) were identified as independent predictors of progression-free survival (PFS). In the IO-TKI group, patients with <3 metastatic organs had longer PFS than those with ≥3 metastatic organs. No significant difference in PFS was observed between <3 and ≥3 metastatic organs in the IO-IO group. This differential effect of the metastatic burden was confirmed by a significant interaction between the treatment group and number of metastatic organs (p for interaction=0.001) . continued ✉ Dr. Takahiro Osawa, Department of Urology, Hokkaido University, Graduate School of Medicine, N15 W7 Kita-ku, Sapporo, 060-8638 Japan. Tel: +81 117065966, Fax: +81 117067853, e-mail: [taka0573@gmail.com](taka0573@gmail.com) Received August 12, 2025 | Revised September 22, 2025 | Accepted October 1, 2025 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. ©2026 The Author(s) . Anticancer Research is published by the International Institute of Anticancer Research. Conclusion: The number of metastatic organs affects the efficacy of IO-TKI but has no effect on the efficacy of IO-IO treatment. We recommend considering the number of metastatic organs as an additional prognostic factor to optimize treatment selection for patients with mRCC. Keywords: Renal cell carcinoma, dual immune checkpoint blockade, immune-oncology combination therapy, systemic treatment, tyrosine kinase inhibitors, metastasis. Introduction In the last decade, the treatment landscape for advanced renal cell carcinoma (RCC) has been revolutionized by recent advances in immunotherapy. Dual immune checkpoint blockade (IO-IO) and the combination of immunotherapy with tyrosine kinase inhibitors (IO-TKI) have emerged as two promising approaches in the management of metastatic RCC (mRCC) (1-4) . IO-IO regimens, which typically include agents targeting complementary immune pathways, aim to synergistically enhance the anti-tumor immune response, while IO-TKI combinations not onl

FAQs

What treatment strategies were compared in the study?

The study compared dual immune checkpoint blockade (IO-IO) with a combination of immunotherapy and tyrosine kinase inhibitors (IO-TKI) for metastatic renal cell carcinoma.

How was the number of metastatic organs evaluated for its prognostic impact?

The analysis focused on metastatic organ count and assessed its relationship with survival using multivariable Cox proportional hazards models and treatment-by-metastatic-organ interaction terms.

What was the main finding regarding efficacy differences between IO-TKI and IO-IO?

The number of metastatic organs affected outcomes in the IO-TKI group but showed no effect on progression-free survival in the IO-IO group.

Sep 28, 2026

Uploaded by mieayamfan