Comparison of first-line immuno-oncology combinations with molecular targeted therapy in patients with advanced renal cell carcinoma undergoing hemodialysis: a real-world multicenter retrospective study

Kosuke Ueda; Hiroki Kurata; Yoji Murakami; Akinori Minato; Masaki Shiota; Shotaro Nakanishi; Keijiro Kiyoshima; Toru Inoue; Hisaji Kumagae; Shinichiro Irie; Mitsuru Noguchi; Shuichi Tatarano; Hiroshi Matsuzaki; Yuji Tokuda; Atsuro Sawada; Tatsuro Abe; Yoshinori Oshiro; Shuji Harada; Tsukasa Igawa

doi:10.1007/s10147-025-02933-9

Comparison of first-line immuno-oncology combinations with molecular targeted therapy in patients with advanced renal cell carcinoma undergoing hemodialysis: a real-world multicenter retrospective study

Int J Clin Oncol. 2026 Jan;31(1):160-171. doi: 10.1007/s10147-025-02933-9. Epub 2025 Dec 2.

Authors

Kosuke Ueda¹, Hiroki Kurata², Yoji Murakami³, Akinori Minato⁴, Masaki Shiota⁵, Shotaro Nakanishi⁶, Keijiro Kiyoshima⁷, Toru Inoue⁸, Hisaji Kumagae⁹, Shinichiro Irie¹⁰, Mitsuru Noguchi¹¹, Shuichi Tatarano¹², Hiroshi Matsuzaki¹³, Yuji Tokuda¹⁴, Atsuro Sawada¹⁵, Tatsuro Abe¹⁶, Yoshinori Oshiro¹⁷, Shuji Harada¹⁸, Tsukasa Igawa¹⁹

Affiliations

¹ Department of Urology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan. ueda_kousuke@med.kurume-u.ac.jp.
² Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
³ Department of Urology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
⁴ Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
⁵ Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
⁶ Department of Urology, Graduate School of Medicine, University of the Ryukyus, Ginowan, Japan.
⁷ Department of Urology, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan.
⁸ Department of Urology, Faculty of Medicine, Oita University, Yufu, Japan.
⁹ Department of Urology, Omuta City General Hospital, Omuta, Japan.
¹⁰ Department of Urology, Aso Iizuka Hospital, Iizuka, Japan.
¹¹ Department of Urology, Faculty of Medicine, Saga University, Saga, Japan.
¹² Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
¹³ Department of Urology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
¹⁴ Department of Urology, Koga Hospital 21, Kurume, Japan.
¹⁵ Department of Urology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
¹⁶ Division of Urology, Harasanshin Hospital, Fukuoka, Japan.
¹⁷ Department of Urology, Chubu Tokushukai Hospital, Okinawa, Japan.
¹⁸ Department of Urology, Shin-Yukuhashi Hospital, Yukuhashi, Japan.
¹⁹ Department of Urology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.

PMID: 41329256
DOI: 10.1007/s10147-025-02933-9

Abstract

Background: Patients with advanced renal cell carcinoma (RCC) undergoing hemodialysis are often excluded from clinical trials. We aimed to evaluate real-world outcomes of first-line molecular targeted therapy (MTT) and immuno-oncology (IO) combination therapies in patients with advanced RCC receiving hemodialysis.

Methods: We retrospectively analyzed data from 88 patients undergoing hemodialysis who received first-line systemic therapy for advanced RCC at 18 institutions in Japan between 2008 and 2023. Patients were divided into three groups by first-line regimen: MTT (n = 53), IO-IO (n = 18), or IO-tyrosine kinase inhibitor (IO-TKI, n = 17). Treatment response, progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) were evaluated. Prognostic factors were identified using univariate and multivariate Cox regression analyses.

Results: The median PFS and OS were 3.9 and 18.9 months, respectively. The IO-IO and IO-TKI groups achieved significantly longer PFS than that in the MTT group (median PFS 3.5, 5.4, and 7.5 months, respectively; p = 0.003); OS did not differ significantly between the groups. Grade ≥ 3 TRAEs occurred in 30.2%, 33.3%, and 41.2% of the MTT, IO-IO, and IO-TKI groups, respectively. Multivariate analysis identified poor Eastern Cooperative Oncology Group performance status, longer hemodialysis duration (≥ 10 years), and first-line regimen as independent PFS predictors. International Metastatic RCC Database Consortium risk classification and hemodialysis duration independently predicted OS.

Conclusions: Systemic therapy, including IO-IO and IO-TKI regimens, demonstrated acceptable safety profiles for patients with advanced RCC undergoing hemodialysis. IO combination therapy significantly improved PFS, supporting its utility as a first-line treatment option.

Keywords: Hemodialysis; Immune checkpoint inhibitors; Molecular targeted therapy; Renal cell carcinoma; Tyrosine kinase inhibitors.

Publication types

Multicenter Study
Comparative Study

MeSH terms

Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols* / adverse effects
Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
Carcinoma, Renal Cell* / drug therapy
Carcinoma, Renal Cell* / mortality
Carcinoma, Renal Cell* / pathology
Carcinoma, Renal Cell* / therapy
Female
Humans
Japan
Kidney Neoplasms* / drug therapy
Kidney Neoplasms* / mortality
Kidney Neoplasms* / pathology
Kidney Neoplasms* / therapy
Male
Middle Aged
Molecular Targeted Therapy* / methods
Progression-Free Survival
Protein Kinase Inhibitors / administration & dosage
Protein Kinase Inhibitors / therapeutic use
Renal Dialysis*
Retrospective Studies

Substances

Protein Kinase Inhibitors