Onkologie. 2025:19(2):69-75 | DOI: 10.36290/xon.2025.015

Current options for adjuvant treatment of urothelial carcinomas

Jindřich Kopecký1, Alexandr Poprach2
1 Klinika onkologie a radioterapie, Fakultní nemocnice Hradec Králové
2 Klinika komplexní onkologické péče, Masarykův onkologický ústav, Brno

Urothelial carcinoma (UC) represents a significant oncological challenge with high mortality, particularly in advanced stages. Adjuvant therapy, whether chemotherapy or immunotherapy, plays a crucial role in reducing the risk of relapse and improving survival after radical surgery. This review summarises current knowledge on the use of adjuvant treatment in UC and upper tract urothelial carcinoma (UTUC), including its histological variants. The most established modality remains cisplatin-based chemotherapy, which has demonstrated benefits, particularly in patients at high risk of relapse (pT3-4, N+) without prior neoadjuvant chemotherapy. A major breakthrough has been the introduction of immunotherapy, especially nivolumab, whose efficacy was confirmed in the randomised CheckMate 274 trial, with the most significant be­nefit observed in patients with high PD-L1 expression. The role of adjuvant therapy in histological variants of UC remains unclear and requires further research. The future direction of adjuvant treatment involves the identification of predictive biomarkers, including circulating tumour DNA (ctDNA) and developing personalised strategies that consider the molecular and immune characteristics of the tumour. Optimising patient selection using liquid biopsies and other biomarkers is key to improving long-term outcomes.

Keywords: urothelial carcinoma, upper tract urothelial carcinoma, immunotherapy, chemotherapy.

Accepted: April 25, 2025; Published: May 2, 2025  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Kopecký J, Poprach A. Current options for adjuvant treatment of urothelial carcinomas. Onkologie. 2025;19(2):69-75. doi: 10.36290/xon.2025.015.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • PDF will be unlocked 2.5.2026

    References

    1. Kirkali Z, Chan T, Manoharan M, et al. Bladder cancer: epidemiology, staging and grading, and diagnosis. Urology. 2005;66(6 Suppl 1):4-34. Go to original source... Go to PubMed...
    2. Humphrey PA, Moch H, Cubilla AL, et al. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part B: Prostate and Bladder Tumours. Eur Urol. 2016;70(1):106-119. Go to original source... Go to PubMed...
    3. Ogbue O, Haddad A, Almassi N, et al. Overview of histologic variants of urothelial carcinoma: current trends and narrative review on treatment outcomes. Transl Androl. J Urol. 2022;11(6):877-901. Go to original source... Go to PubMed...
    4. Vetterlein MW, Wankowicz SAM, Seisen T, et al. Neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer with variant histology. Cancer. 2017;123(22):4346-4355. Go to original source... Go to PubMed...
    5. Catto JW, Yates DR, Rehman I, et al. Behavior of urothelial carcinoma with respect to anatomical location. J Urol. 2007;177(5):1715-1720. Go to original source... Go to PubMed...
    6. Cognetti F, Ruggeri EM, Felici A, et al. Adjuvant chemotherapy with cisplatin and gemcitabine versus chemotherapy at relapse in patients with muscle-invasive bladder cancer submitted to radical cystectomy: an Italian, multicenter, randomized phase III trial. Ann Oncol. 2012;23(3):695-700. Go to original source... Go to PubMed...
    7. Paz-Ares LG, Solsona E, Esteban E, et al. Randomized phase III trial comparing adjuvant paclitaxel/gemcitabine/cisplatin (PGC) to observation in patients with resected invasive bladder cancer: Results of the Spanish Oncology Genitourinary Group (SOGUG) 99/01 study. Journal of Clinical Oncology. 2010;28(18_suppl):LBA4518-LBA4518. Go to original source...
    8. Sternberg CN, Skoneczna I, Kerst JM, et al. Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial. Lancet Oncol. 2015;16(1):76-86. Go to original source... Go to PubMed...
    9. Adjuvant Chemotherapy for Muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis of Individual Participant Data from Randomised Controlled Trials. Eur Urol. 2022;81(1):50-61. Go to original source... Go to PubMed...
    10. Kronstedt S, Saffati G, Hinojosa-Gonzalez DE, et al. Early Adjuvant Chemotherapy Improves Survival in Muscle Invasive Bladder Cancer: A Systematic Review and Meta-analysis. Urology. 2024;194:289-294. doi: 10.1016/j.urology.2024.08.067. Epub 2024 Sep 2. PMID: 39233282. Go to original source... Go to PubMed...
    11. Cai Z, Jin H, Chen J, et al. Adjuvant chemotherapy in patients with locally advanced bladder cancer after neoadjuvant chemotherapy and radical cystectomy: a systematic review and pooled analysis. Translational Andrology and Urology. 2021;10(1):283-291. Go to original source... Go to PubMed...
    12. Galsky MD, Hahn NM, Rosenberg J, et al. Treatment of patients with metastatic urothelial cancer "unfit" for Cisplatin-based chemotherapy. J Clin Oncol. 2011;29(17):2432-2438. Go to original source... Go to PubMed...
    13. Powles T, Park SH, Voog E, et al. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. New England Journal of Medicine. 2020;383(13):1218-1230. Go to original source... Go to PubMed...
    14. Bamias A, Davis ID, Galsky MD, et al. Atezolizumab monotherapy versus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis from a randomised, controlled, phase 3 study. The Lancet Oncology. 2024;25(1):46-61. Go to original source... Go to PubMed...
    15. van der Heijden MS, Sonpavde G, Powles T, et al. Nivolumab plus Gemcitabine-Cisplatin in Advanced Urothelial Carcinoma. N Engl J Med. 2023;389(19):1778-1789. Go to original source... Go to PubMed...
    16. Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med. 2017;376(11):1015-1026. Go to original source... Go to PubMed...
    17. Balar AV, Castellano D, O'Donnell PH, et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. The Lancet Oncology. 2017;18(11):1483-1492. Go to original source... Go to PubMed...
    18. Bellmunt J, Hussain M, Gschwend JE, et al. Adjuvant atezolizumab versus observation in muscle-invasive urothelial carcinoma (IMvigor010): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(4):525-537. Go to original source... Go to PubMed...
    19. Powles T, Assaf ZJ, Degaonkar V, et al. Updated Overall Survival by Circulating Tumor DNA Status from the Phase 3 IMvigor010 Trial: Adjuvant Atezolizumab Versus Observation in Muscle-invasive Urothelial Carcinoma. Eur Urol. 2024;85(2):114-122. Go to original source... Go to PubMed...
    20. Apolo AB, Ballman KV, Sonpavde G, et al. Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma. N Engl J Med. 2025;392(1):45-55. doi: 10.1056/NEJMoa2401726. Epub 2024 Sep 15. PMID: 39282902; PMCID: PMC11698643. Go to original source... Go to PubMed...
    21. Powles T, Catto JWF, Galsky MD, et al. Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer. N Engl J Med. 2024;391(19):1773-1786. Go to original source... Go to PubMed...
    22. Hoimes CJ, Loriot Y, Bedke J, et al. Perioperative enfortumab vedotin (EV) plus pembrolizumab (pembro) versus chemotherapy in cisplatin-eligible patients (pts) with muscle-invasive bladder cancer (MIBC): Phase 3 KEYNOTE-B15/EV-304. Journal of Clinical Oncology. 2023;41(6_suppl): TPS588-TPS588. Go to original source...
    23. Bajorin DF, Witjes JA, Gschwend JE, et al. Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. New England Journal of Medicine. 2021;384(22):2102-2114. Go to original source... Go to PubMed...
    24. Galsky MD, Witjes JA, Gschwend JE, et al. Adjuvant Nivolumab in High-Risk Muscle-Invasive Urothelial Carcinoma: Expanded Efficacy From CheckMate 274. Journal of Clinical Oncology. January 2025;(43):1. Go to original source... Go to PubMed...
    25. Liang FX, Bosland MC, Huang H, et al. Cellular basis of urothelial squamous metaplasia: roles of lineage heterogeneity and cell replacement. J Cell Biol. 2005;171(5):835-44. Go to original source... Go to PubMed...
    26. Sfakianos JP, Cha EK, Iyer G, et al. Genomic Characterization of Upper Tract Urothelial Carcinoma. Eur Urol. 2015;68(6):970-977. Go to original source... Go to PubMed...
    27. van der Post RS, Kiemeney LA, Ligtenberg MJ, et al. Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers. J Med Genet. 2010;47(7):464-470. Go to original source... Go to PubMed...
    28. Birtle A, Johnson M, Chester J, et al. Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial. Lancet. 2020;395(10232):1268-1277. Go to original source... Go to PubMed...
    29. Birtle AJ, Jones R, Chester J, et al. Improved Disease-Free Survival With Adjuvant Chemotherapy After Nephroureterectomy for Upper Tract Urothelial Cancer: Final Results of the POUT Trial. Journal of Clinical Oncology. 2024;42(13):1466-1471. Go to original source... Go to PubMed...
    30. Witjes JA, Babjuk M, Bellmunt J, et al. EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer-An International Collaborative Multistakeholder Effort(†): Under the Auspices of the EAU-ESMO Guidelines Committees. Eur Urol. 2020;77(2):223-250. Go to original source... Go to PubMed...
    31. Black AJ and Black PC Variant histology in bladder cancer: diagnostic and clinical implications. Transl Cancer Res. 2020;9(10):6565-6575.
    32. Minato A, Murooka K, Okumura Y, et al. Efficacy of Platinum-based Chemotherapy in Patients With Metastatic Urothelial Carcinoma With Variant Histology. In Vivo. 2024;38(2):873-880. Go to original source... Go to PubMed...
    33. Lobo N, Shariat SF, Guo CC, et al. What Is the Significance of Variant Histology in Urothelial Carcinoma? European Urology Focus. 2020;6(4):653-663. Go to original source... Go to PubMed...

    Return to the content


    Oncology

    Madam, Sir,
    please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
    Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

    I declare:

    1. that I have met the above instruction
    2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited

    No
    Yes

    If your statement is not true, please be aware
    that brings the risk of danger to their health or the health of others.