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Current trends in the promising immune checkpoint inhibition and radiotherapy combination for locally advanced and metastatic urothelial carcinoma

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Abstract

Locally advanced and metastatic urothelial carcinoma (UC) remains a challenging malignancy, though several novel therapeutic drugs have been developed in recent years. Over the past decade, immune checkpoint inhibitors (ICI) have shifted the paradigm of therapeutic strategies for UC; however, only a limited number of patients respond to ICI. Since radiotherapy (RT) is widely known to induce systemic immune activation, it may boost the efficacy of ICI. Conversely, RT also causes exhaustion of cytotoxic T cells, and the activation and recruitment of immunosuppressive cells; ICI may help overcome these immunosuppressive effects. Therefore, the combination of ICI and RT has attracted attention in recent years. The therapeutic benefits of this combination therapy and its optimal regimen have not yet been determined through prospective studies. Therefore, this review article aimed to provide an overview of the current preclinical and clinical studies that illustrate the underlying mechanisms and explore the optimization of the RT regimen along with the ICI and RT combination sequence. We also analyzed ongoing prospective studies on ICI and RT combination therapies for metastatic UC. We noted that the tumor response to ICI and RT combination seemingly differs among cancer types. Thus, our findings highlight the need for well-designed prospective trials to determine the optimal combination of ICI and RT for locally advanced and metastatic UC.

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Acknowledgements

We would like to thank Editage (www.editage.com) for English language editing.

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Authors and Affiliations

  1. Department of Urology and Andrology, Kansai Medical University Hospital, 2-5-1 Shin-machi, Hirakata-shi, Osaka, 573-1010, Japan

    Takeshi Sano

  2. Department of Urology, Graduate School of Medicine, Kyoto University, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Takeshi Sano, Ryoichi Saito, Kaoru Murakami, Yuki Kita, Kimihiko Masui, Takayuki Goto & Takashi Kobayashi

  3. Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Rihito Aizawa & Takashi Mizowaki

  4. Institute for Integrated Radiation and Nuclear Science, Kyoto University, 2 Asashiro-Nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494, Japan

    Tsubasa Watanabe

Authors
  1. Takeshi Sano
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  2. Ryoichi Saito
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  3. Rihito Aizawa
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  4. Tsubasa Watanabe
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  6. Yuki Kita
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  7. Kimihiko Masui
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  8. Takayuki Goto
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  9. Takashi Mizowaki
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  10. Takashi Kobayashi
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Contributions

TS, TM, and TK contributed to the study conception and design. TS, RS, RA, TW, and KM collected the related references and participated in discussion. The first draft of the manuscript was written by TS, and all the authors commented on previous versions of the manuscript. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Takashi Kobayashi.

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Sano, T., Saito, R., Aizawa, R. et al. Current trends in the promising immune checkpoint inhibition and radiotherapy combination for locally advanced and metastatic urothelial carcinoma. Int J Clin Oncol 28, 1573–1584 (2023). https://doi.org/10.1007/s10147-023-02421-y

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  • DOI: https://doi.org/10.1007/s10147-023-02421-y

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