Efficacy of cisplatin-based neoadjuvant chemotherapy and risk factors for residual extravesical disease in muscle-invasive bladder cancer: insights from a nationwide cohort

Ryoichi Saito^{1

2}, Rikiya Taoka³, Jun Miki^{4

5}, Wataru Fukuokaya^{4

5}, Yoshiyuki Matsui⁶, Shingo Hatakeyama⁷, Takashi Kawahara⁸, Ayumu Matsuda⁶, Taketo Kawai^{9

10}, Tomokazu Sazuka¹¹, Minoru Kato¹², Takeshi Sano^{13

14}, Fumihiko Urabe^{4

15}, Soki Kashima¹⁶, Hirohito Naito^{3

17}, Yoji Murakami¹⁸, Makito Miyake¹⁹, Kei Daizumoto²⁰, Yuto Matsushita²¹, Takuji Hayashi²², Junichi Inokuchi^{23

24}, Yusuke Sugino²⁵, Kenichiro Shiga²⁶, Noriya Yamaguchi²⁷, Shingo Yamamoto²⁸, Keiji Yasue^{4

29}, Takashige Abe³⁰, Shotaro Nakanishi²⁴, Katsuyoshi Hashine³¹, Masato Fujii³², Kiyoaki Nishihara³³, Hiroaki Matsumoto³⁴, Shuichi Tatarano³⁵, Koichiro Wada³⁶, Sho Sekito^{25

36}, Ryo Maruyama³⁷, Naotaka Nishiyama³⁸, Hiroyuki Nishiyama⁸, Hiroshi Kitamura³⁹, Hidefumi Kinoshita¹³; Japan Urological Oncology Group

Affiliations

¹ Department of Urology and Andrology, Kansai Medical University, Hirakata, Japan. rsaito@kuhp.kyoto-u.ac.jp.
² Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan. rsaito@kuhp.kyoto-u.ac.jp.
³ Department of Urology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
⁴ Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
⁵ Department of Urology, The Jikei University Kashiwa Hospital, Chiba, Japan.
⁶ Department of Urology, National Cancer Center Hospital, Tokyo, Japan.
⁷ Department of Urology, Hirosaki University Graduate School of Medicine, Aomori, Japan.
⁸ Department of Urology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
⁹ Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
¹⁰ Department of Urology, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Japan.
¹¹ Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
¹² Department of Urology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
¹³ Department of Urology and Andrology, Kansai Medical University, Hirakata, Japan.
¹⁴ Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
¹⁵ Department of Urology, Jikei University Hospital, Tokyo, Japan.
¹⁶ Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.
¹⁷ Department of Urology, Kurashiki Central Hospital, Okayama, Japan.
¹⁸ Department of Urology, Graduate School of Life Science, Kumamoto University, Kumamoto, Japan.
¹⁹ Department of Urology, Nara Medical University, Nara, Japan.
²⁰ Department of Urology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
²¹ Department of Urology, Hamamatsu University School of Medicine, Shizuoka, Japan.
²² Department of Urology, Osaka International Cancer Institute, Osaka, Japan.
²³ Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
²⁴ Department of Urology, Graduate School of Medicine, University of the Ryukyus, Ginowan, Japan.
²⁵ Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Mie, Japan.
²⁶ Department of Urology, Harasanshin General Hospital, Fukuoka, Japan.
²⁷ Department of Urology, Faculty of Medicine, Tottori University, Tottori, Japan.
²⁸ Department of Urology, Hyogo Medical University, Hyogo, Japan.
²⁹ Department of Urology, The Jikei University Katsushika Medical Center, Tokyo, Japan.
³⁰ Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
³¹ Department of Urology, National Hospital Organization Shikoku Cancer Center, Ehime, Japan.
³² Department of Urology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
³³ Department of Urology, Kurume University School of Medicine, Fukuoka, Japan.
³⁴ Department of Urology Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan.
³⁵ Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
³⁶ Department of Urology, Faculty of Medicine, Shimane University, Shimane, Japan.
³⁷ Department of Urology, Aichi Cancer Center Hospital, Aichi, Japan.
³⁸ Department of Urology, Niigata University Graduate School of Medicine, Niigata, Japan.
³⁹ Department of Urology, Faculty of Medicine, University of Toyama, Toyama, Japan.

PMID: 40690100
DOI: 10.1007/s10147-025-02833-y

Efficacy of cisplatin-based neoadjuvant chemotherapy and risk factors for residual extravesical disease in muscle-invasive bladder cancer: insights from a nationwide cohort

Ryoichi Saito et al. Int J Clin Oncol. 2025 Oct.

. 2025 Oct;30(10):2106-2117.

doi: 10.1007/s10147-025-02833-y. Epub 2025 Jul 21.

Authors

Affiliations

¹ Department of Urology and Andrology, Kansai Medical University, Hirakata, Japan. rsaito@kuhp.kyoto-u.ac.jp.
² Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan. rsaito@kuhp.kyoto-u.ac.jp.
³ Department of Urology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
⁴ Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
⁵ Department of Urology, The Jikei University Kashiwa Hospital, Chiba, Japan.
⁶ Department of Urology, National Cancer Center Hospital, Tokyo, Japan.
⁷ Department of Urology, Hirosaki University Graduate School of Medicine, Aomori, Japan.
⁸ Department of Urology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
⁹ Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
¹⁰ Department of Urology, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Japan.
¹¹ Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan.
¹² Department of Urology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
¹³ Department of Urology and Andrology, Kansai Medical University, Hirakata, Japan.
¹⁴ Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
¹⁵ Department of Urology, Jikei University Hospital, Tokyo, Japan.
¹⁶ Department of Urology, Akita University Graduate School of Medicine, Akita, Japan.
¹⁷ Department of Urology, Kurashiki Central Hospital, Okayama, Japan.
¹⁸ Department of Urology, Graduate School of Life Science, Kumamoto University, Kumamoto, Japan.
¹⁹ Department of Urology, Nara Medical University, Nara, Japan.
²⁰ Department of Urology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
²¹ Department of Urology, Hamamatsu University School of Medicine, Shizuoka, Japan.
²² Department of Urology, Osaka International Cancer Institute, Osaka, Japan.
²³ Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
²⁴ Department of Urology, Graduate School of Medicine, University of the Ryukyus, Ginowan, Japan.
²⁵ Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Mie, Japan.
²⁶ Department of Urology, Harasanshin General Hospital, Fukuoka, Japan.
²⁷ Department of Urology, Faculty of Medicine, Tottori University, Tottori, Japan.
²⁸ Department of Urology, Hyogo Medical University, Hyogo, Japan.
²⁹ Department of Urology, The Jikei University Katsushika Medical Center, Tokyo, Japan.
³⁰ Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
³¹ Department of Urology, National Hospital Organization Shikoku Cancer Center, Ehime, Japan.
³² Department of Urology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
³³ Department of Urology, Kurume University School of Medicine, Fukuoka, Japan.
³⁴ Department of Urology Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan.
³⁵ Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
³⁶ Department of Urology, Faculty of Medicine, Shimane University, Shimane, Japan.
³⁷ Department of Urology, Aichi Cancer Center Hospital, Aichi, Japan.
³⁸ Department of Urology, Niigata University Graduate School of Medicine, Niigata, Japan.
³⁹ Department of Urology, Faculty of Medicine, University of Toyama, Toyama, Japan.

PMID: 40690100
DOI: 10.1007/s10147-025-02833-y

Abstract

Background: Cisplatin-based neoadjuvant chemotherapy (NAC) improves survival in muscle-invasive bladder cancer (MIBC) as long as disease progression does not occur during treatment. However, predictors of NAC sensitivity remain elusive in clinical practice. This study evaluated the efficacy of NAC followed by radical cystectomy (NAC-RC) in cStage II-IIIA MIBC and identified the risk factors associated with residual extravesical disease.

Methods: Clinical data from 1474 patients who underwent radical cystectomy for cStage II-IIIA urothelial carcinoma were collected from 36 institutions of the Japanese Urological Oncology Group. Overall survival (OS) and non-urinary tract recurrence-free survival (NUT-RFS) were compared between the NAC-RC and upfront RC groups using the Kaplan-Meier method adjusted by inverse probability of treatment weighting. Logistic regression was used to identify independent risk factors for RED.

Results: Pathological complete response (pT0N0) was achieved in 33.1 and 20.2% of cStage II and IIIA patients in the NAC-RC group, respectively, compared with 16.3 and 4.5% in the RC group. NAC significantly improved the OS and NUT-RFS in the IPTW-adjusted cohort. BCG-unresponsiveness, low serum albumin levels, and a high neutrophil-to-lymphocyte ratio were independent predictors of RED in the NAC-RC cohort. Squamous differentiation was associated with worse prognosis but a favorable response to NAC in some tumors.

Conclusions: Cisplatin-based NAC improves outcomes in patients with cStage II-IIIA MIBC, including some tumors with squamous differentiation; however, its benefits may be limited in BCG-unresponsive cases. Given the biological heterogeneity of urothelial cancer, individualized treatment planning that integrates biological features and treatment history is needed for patients with MIBC.

Keywords: BCG unresponsive; Chemosensitivity; Muscle-invasive bladder cancer; Neoadjuvant chemotherapy; Residual Extravesical Disease; Squamous differentiation.

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Conflict of interest statement

Declarations. Ethical approval: This study was approved by the Institutional Review Board of Kagawa University. The reference number is 2021-140. Informed consent: The opt-out method was used to obtain consent from participants using posters and/or websites. Conflict of interest: The authors declare no conflict of interest.

References

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Efficacy of cisplatin-based neoadjuvant chemotherapy and risk factors for residual extravesical disease in muscle-invasive bladder cancer: insights from a nationwide cohort

Affiliations

Efficacy of cisplatin-based neoadjuvant chemotherapy and risk factors for residual extravesical disease in muscle-invasive bladder cancer: insights from a nationwide cohort

Authors

Affiliations

Abstract

Conflict of interest statement

References

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical