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Clinical Studies

Efficacy and safety of tislelizumab combined with chemotherapy for locally advanced penile cancer: a prospective, single-arm clinical study

British Journal of Cancer volume 134, pages 764–771 (2026)Cite this article

Subjects

Abstract

Background

Locally advanced penile squamous cell carcinoma (PSCC) generally has a poor prognosis. Our aim was to access the efficacy and safety of programmed cell death protein 1 (PD-1) inhibitor tislelizumab combined with chemotherapy for locally advanced PSCC.

Methods

In this prospective, single-arm clinical study, eligible patients received Nab-Paclitaxel (175 mg/m2 D1), Cisplatin (70 mg/m2 in 3 days), Bleomycin (30 mg D1, 8), and tislelizumab (200 mg D1) every 3 weeks for 4–6 cycles, followed by consolidative treatment if necessary. The primary endpoint was objective response rate (ORR) and progression-free survival (PFS).

Results

Of all 20 enrolled patients, 75.0% (15/20) had a history of previous penectomy and were recurrence cases. The median treatment cycles was 4 (range: 2-6). The ORR reached 75.0%. 35.0% (7/20) of patients underwent consolidative surgery, and 55.0% (11/20) received maintenance immunotherapy (median 7 cycles). At median follow-up of 29.3 months, the median PFS and the median overall survival (OS) were 12.5 months (95% CI 7.4-NE), 22.8 months (95% CI 13.7-NE), respectively. Grade≥3 treatment-related adverse events (TRAEs) were observed in 40% (8/20) patients. No treatment-related deaths occurred.

Conclusions

The combination of tislelizumab with chemotherapy demonstrated promising antitumor efficacy in locally advanced PSCC, with a manageable safety profile.

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Fig. 1: Trial profile of the study.
Fig. 2: Antitumor activity in patients with locally advanced penile cancer receiving tislelizumab combined with chemotherapy.
Fig. 3: Survival outcomes in patients with locally advanced penile cancer receiving tislelizumab combined with chemotherapy.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Montes Cardona CE, García-Perdomo HA. Incidence of penile cancer worldwide: systematic review and meta-analysis. Rev Panam Salud Publica. 2017;41:e117 https://doi.org/10.26633/rpsp.2017.117.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Bleeker MC, Heideman DA, Snijders PJ, Horenblas S, Dillner J, Meijer CJ. Penile cancer: epidemiology, pathogenesis and prevention. World J Urol. 2009;27:141–50.

    Article  CAS  PubMed  Google Scholar 

  3. Thomas A, Necchi A, Muneer A, Tobias-Machado M, Tran ATH, Van Rompuy AS, et al. Penile cancer. Nat Rev Dis Prim. 2021;7:11.

    Article  PubMed  Google Scholar 

  4. Guo YL, Na YQ, Ye ZQ, Huang J, Zhang X, Wei Qiang, et al. The 2022 Chinese guideline for the diagnosis and treatment of urological and andrological diseases. Science and Technology Press, 2022:245–71.

  5. Azizi M, Aydin AM, Hajiran A, Lai A, Kumar A, Peyton CC, et al. Systematic review and meta-analysis-is there a benefit in using neoadjuvant systemic chemotherapy for locally advanced penile squamous cell carcinoma?. J Urol. 2020;203:1147–55.

    Article  PubMed  Google Scholar 

  6. Wang J, Pettaway CA, Pagliaro LC. Treatment for metastatic penile cancer after first-line chemotherapy failure: analysis of response and survival outcomes. Urology. 2015;85:1104–10.

    Article  CAS  PubMed  Google Scholar 

  7. Cocks M, Taheri D, Ball MW, Bezerra SM, Del Carmen Rodriguez M, Ricardo BFP, et al. Immune-checkpoint status in penile squamous cell carcinoma: a North American cohort. Hum Pathol. 2017;59:55–61.

    Article  CAS  PubMed  Google Scholar 

  8. Hahn AW, Chahoud J, Campbell MT, Karp DD, Wang J, Stephen B, et al. Pembrolizumab for advanced penile cancer: a case series from a phase II basket trial. Invest N Drugs. 2021;39:1405–10.

    Article  CAS  Google Scholar 

  9. Baweja A, Mar N. Metastatic penile squamous cell carcinoma with dramatic response to combined checkpoint blockade with ipilimumab and nivolumab. J Oncol Pharm Pr. 2021;27:212–5.

    Article  Google Scholar 

  10. Lee A, Keam SJ. Tislelizumab: First Approval. Drugs. 2020;80:617–24.

    Article  CAS  PubMed  Google Scholar 

  11. Zhang T, Song X, Xu L, Ma J, Zhang Y, Gong W, et al. The binding of an anti-PD-1 antibody to FcγRΙ has a profound impact on its biological functions. Cancer Immunol Immunother. 2018;67:1079–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wang J, Lu S, Yu X, Hu Y, Sun Y, Wang Z, et al. Tislelizumab Plus chemotherapy vs chemotherapy alone as first-line treatment for advanced squamous non-small-cell lung cancer: a Phase 3 randomized clinical trial. JAMA Oncol. 2021;7:709–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Xu J, Bai Y, Xu N, Li E, Wang B, Wang J, et al. Tislelizumab plus chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma and gastric/gastroesophageal junction adenocarcinoma. Clin Cancer Res. 2020;26:4542–50.

    Article  CAS  PubMed  Google Scholar 

  14. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74:12–49.

    PubMed  Google Scholar 

  15. NCCN Clinical Practice Guidelines in Oncology. Penile Cancer (Version 1. 2026). 2025. https://www.nccn.org/professionals/physician_gls/pdf/penile.pdf.

  16. Chahoud J, Kohli M, Spiess PE. Management of Advanced Penile Cancer. Mayo Clin Proc. 2021;96:720–32.

    Article  PubMed  Google Scholar 

  17. Chahoud J, Tamil M, Necchi A. Second line salvage systemic therapy for advanced penile cancer. Urol Oncol. 2022;40:229–34.

    Article  PubMed  Google Scholar 

  18. Novara G, Galfano A, De Marco V, Artibani W, Ficarra V. Prognostic factors in squamous cell carcinoma of the penis. Nat Clin Pr Urol. 2007;4:140–6.

    Article  Google Scholar 

  19. Leijte JA, Kirrander P, Antonini N, Windahl T, Horenblas S. Recurrence patterns of squamous cell carcinoma of the penis: recommendations for follow-up based on a two-centre analysis of 700 patients. Eur Urol. 2008;54:161–8.

    Article  PubMed  Google Scholar 

  20. de Vries HM, Ottenhof SR, van der Heijden MS, Pos FJ, Horenblas S, Brouwer OR. Management of the penile squamous cell carcinoma patient after node positive radical inguinal lymph node dissection: current evidence and future prospects. Curr Opin Urol. 2020;30:223–8.

    Article  PubMed  Google Scholar 

  21. Pagliaro LC, Williams DL, Daliani D, Williams MB, Osai W, Kincaid M, et al. Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy for metastatic penile cancer: a phase II study. J Clin Oncol. 2010;28:3851–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Nicholson S, Hall E, Harland SJ, Chester JD, Pickering L, Barber J, et al. Phase II trial of docetaxel, cisplatin and 5FU chemotherapy in locally advanced and metastatic penis cancer (CRUK/09/001). Br J Cancer. 2013;109:2554–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Xu J, Li G, Zhu SM, Cai QL, Wang Z, Yang X, et al. Neoadjuvant docetaxel, cisplatin and ifosfamide (ITP) combination chemotherapy for treating penile squamous cell carcinoma patients with terminal lymph node metastasis. BMC Cancer. 2019;19:625.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Dickstein RJ, Munsell MF, Pagliaro LC, Pettaway CA. Prognostic factors influencing survival from regionally advanced squamous cell carcinoma of the penis after preoperative chemotherapy. BJU Int. 2016;117:118–25.

    Article  CAS  PubMed  Google Scholar 

  25. Zhu S, Zhang T, Zheng L, Liu H, Song W, Liu D, et al. Combination strategies to maximize the benefits of cancer immunotherapy. J Hematol Oncol. 2021;14:156.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Yu WD, Sun G, Li J, Xu J, Wang X. Mechanisms and therapeutic potentials of cancer immunotherapy in combination with radiotherapy and/or chemotherapy. Cancer Lett. 2019;452:66–70.

    Article  CAS  PubMed  Google Scholar 

  27. Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, de Castro G Jr., et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394:1915–28.

    Article  CAS  PubMed  Google Scholar 

  28. El Zarif T, Nassar AH, Pond GR, Zhuang TZ, Master V, Nazha B, et al. Safety and efficacy of immune checkpoint inhibitors in advanced penile cancer: report from the Global Society of Rare Genitourinary Tumors. J Natl Cancer Inst. 2023;115:1605–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Cotait Maluf F, Trindade K, Preto D, de Almeida Luz M, Medeiros Milhomem Beato P, Assed Bastos D, et al. Pembrolizumab Plus Platinum-Based Chemotherapy for Patients With Advanced Penile Cancer: The Nonrandomized HERCULES (LACOG 0218) Clinical Trial. JAMA Oncol. 2025 e253266. https://doi.org/10.1001/jamaoncol.2025.3266.

  30. Dhasthakeer U, Jha AN, Gupta AK. Comparison of efficacy and toxicity of chemotherapeutic regimens used as adjuvant and/or neoadjuvant chemotherapy in penile cancer patients. Curr Probl Cancer. 2025;55:101185.

    Article  PubMed  Google Scholar 

  31. An X, Guo SJ, Yan R, Xue T, Xiong LB, Ma HL, et al. Neoadjuvant toripalimab plus nimotuzumab combined with taxol-based chemotherapy in locally advanced penile squamous cell carcinoma. Cancer Cell. 2025;43:970–80.e973. https://doi.org/10.1016/j.ccell.2025.03.023.

    Article  CAS  PubMed  Google Scholar 

  32. Gu W, Zhu Y, Ye D. Beyond chemotherapy for advanced disease-the role of EGFR and PD-1 inhibitors. Transl Androl Urol. 2017;6:848–54.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Udager AM, Liu TY, Skala SL, Magers MJ, McDaniel AS, Spratt DE, et al. Frequent PD-L1 expression in primary and metastatic penile squamous cell carcinoma: potential opportunities for immunotherapeutic approaches. Ann Oncol. 2016;27:1706–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Xue T, Yan R, Han H. Research progress of immune microenvironment and immunotherapy of penile cancer. J Contemp Urol Reprod Oncol. 2022;14:249–52.

    Google Scholar 

  35. Haas GP, Blumenstein BA, Gagliano RG, Russell CA, Rivkin SE, Culkin DJ, et al. Cisplatin, methotrexate and bleomycin for the treatment of carcinoma of the penis: a Southwest Oncology Group study. J Urol. 1999;161:1823–5.

    Article  CAS  PubMed  Google Scholar 

  36. Zou B, Han Z, Wang Z, Bian J, Xu J, Wang H, et al. Neoadjuvant therapy combined with a BMP regimen for treating penile cancer patients with lymph node metastasis: a retrospective study in China. J Cancer Res Clin Oncol. 2014;140:1733–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Corral DA, Sella A, Pettaway CA, Amato RJ, Jones DM, Ellerhorst J. Combination chemotherapy for metastatic or locally advanced genitourinary squamous cell carcinoma: a phase II study of methotrexate, cisplatin and bleomycin. J Urol. 1998;160:1770–4.

    Article  CAS  PubMed  Google Scholar 

  38. Dexeus FH, Logothetis CJ, Sella A, Amato R, Kilbourn R, Fitz K, et al. Combination chemotherapy with methotrexate, bleomycin and cisplatin for advanced squamous cell carcinoma of the male genital tract. J Urol. 1991;146:1284–7.

    Article  CAS  PubMed  Google Scholar 

  39. Hamed KM, Dighriri IM, Baomar AF, Alharthy BT, Alenazi FE, Alali GH, et al. Overview of Methotrexate Toxicity: A Comprehensive Literature Review. Cureus. 2022;14:e29518. https://doi.org/10.7759/cureus.29518.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Marupudi NI, Han JE, Li KW, Renard VM, Tyler BM, Brem H. Paclitaxel: a review of adverse toxicities and novel delivery strategies. Expert Opin Drug Saf. 2007;6:609–21.

    Article  CAS  PubMed  Google Scholar 

  41. EAU-ASCO Collaborative Guidelines on Penile Cancer. 2025. https://uroweb.org/guidelines/penile-cancer.

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Acknowledgements

Not applicable.

Funding

The study was supported by the Beijing Medical Award Foundation (no. YXJL-2020-0951-0409).

Author information

Authors and Affiliations

  1. Department of Urology, Cancer Hospital of Huanxing Chaoyang District Beijing, Beijing, China

    Xingli Shan, Hongsong Bai, Houshan Ning, Chengming Xie, Yonghai Chen, Sijia Xing, Donglin Ni & Linjun Hu

  2. Department of Medical Oncology, Cancer Hospital of Huanxing Chaoyang District Beijing, Beijing, China

    Xiaohua Guo

  3. Department of Hepatology, Ganzhou Institute of Liver Disease, The Fifth People’s Hospital of Ganzhou, Ganzhou, China

    Jingke Zeng

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Contributions

Xingli Shan and Linjun Hu had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Linjun Hu and Xiaohua Guo were involved in the study's concepts and design. All authors (Xingli Shan, Hongsong Bai, Houshan Ning, Chengming Xie, Yonghai Chen, Sijia Xing, Donglin Ni, Xiaohua Guo, Jingke Zeng, Linjun Hu) were involved in the acquisition, analysis and interpretation of data. Jingke Zeng was mainly involved in the treatment of AE (such as liver injury). Linjun Hu and Hongsong Bai supervised the analysis. Hongsong Bai and Chengming Xie were involved in the draft of the manuscript. All authors read, critically revised, and approved the manuscript.

Corresponding authors

Correspondence to Jingke Zeng or Linjun Hu.

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Ethics approval and consent to participate

The study protocol was approved by the Ethics Committee of Beijing Chaoyang Huanxing Cancer Hospital (approval no. 2020-10), and the study was conducted following the Declaration of Helsinki, Good Clinical Practice Guidelines, and Chinese regulatory requirements. Written informed consent was obtained from all patients.

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The authors declare no competing interests.

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Shan, X., Bai, H., Ning, H. et al. Efficacy and safety of tislelizumab combined with chemotherapy for locally advanced penile cancer: a prospective, single-arm clinical study. Br J Cancer 134, 764–771 (2026). https://doi.org/10.1038/s41416-025-03321-w

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