State of the Art of Adjuvant Immunotherapy in Urothelial Cancer: New Developments and Upcoming Changes

Overview

Journal Hum Vaccin Immunother

Specialty Allergy & Immunology

Date 2024 Dec 19

PMID 39701156

Authors

Elisa Tassinari

Linda Danielli

Andrea Marchetti

Matteo Rosellini

Costantino Ricci

Pietro Piazza

Angelo Mottaran

Riccardo Schiavina

Matteo Santoni

Veronica Mollica

Francesco Massari

Affiliations

Soon will be listed here.

Abstract

In recent years, several clinical trials focused on the potential role of immune-checkpoint inhibitors (ICIs) in the adjuvant treatment of muscle-invasive urothelial cancer (UC). Heretofore, only the anti-programmed death protein 1 (anti-PD1) nivolumab received European Medical Agency (EMA) approval for cisplatin-unfit patients. In our work, we deeply analyzed the results of the three pivotal studies in view of the rapidly evolving therapeutic advanced UC's scenario. Furthermore, there are several ongoing research to investigate ICIs and other emerging immune agents in this setting; results are awaited. Additionally, current efforts have been made to assess the role of these agents in earlier disease settings, particularly in high-risk non-muscle-invasive bladder cancer (NMIBC). In our review, we analyzed the potential role of predictive and/or prognostic biomarkers that may improve patient selection and treatment efficacy. To conclude, we highlighted the upcoming changes that could redefine the standard of care for patients with early-stage UC.

References

Aydin A, Baydar D, Hazir B, Babaoglu B, Bilen C . Prognostic significance of pre- and post-treatment PD-L1 expression in patients with primary high-grade non-muscle-invasive bladder cancer treated with BCG immunotherapy. World J Urol. 2020; 38(10):2537-2545. DOI: 10.1007/s00345-019-03065-2. View

Powles T, Assaf Z, Davarpanah N, Banchereau R, Szabados B, Yuen K . ctDNA guiding adjuvant immunotherapy in urothelial carcinoma. Nature. 2021; 595(7867):432-437. DOI: 10.1038/s41586-021-03642-9. View

van der Heijden M, Sonpavde G, Powles T, Necchi A, Burotto M, Schenker M . Nivolumab plus Gemcitabine-Cisplatin in Advanced Urothelial Carcinoma. N Engl J Med. 2023; 389(19):1778-1789. DOI: 10.1056/NEJMoa2309863. View

Black P, Tangen C, Singh P, McConkey D, Lucia M, Lowrance W . Phase 2 Trial of Atezolizumab in Bacillus Calmette-Guérin-unresponsive High-risk Non-muscle-invasive Bladder Cancer: SWOG S1605. Eur Urol. 2023; 84(6):536-544. PMC: 10869634. DOI: 10.1016/j.eururo.2023.08.004. View

Jiang S, Redelman-Sidi G . BCG in Bladder Cancer Immunotherapy. Cancers (Basel). 2022; 14(13). PMC: 9264881. DOI: 10.3390/cancers14133073. View

Uccello M, Adeleke S, Moschetta M, Ghose A, Boussios S . Immunotherapy for advanced urothelial carcinoma (UC): rational and current evidence. Ann Palliat Med. 2023; 12(6):1345-1354. DOI: 10.21037/apm-22-1350. View

Siefker-Radtke A, Cho D, Diab A, Sznol M, Bilen M, Balar A . Bempegaldesleukin plus Nivolumab in First-line Metastatic Urothelial Carcinoma: Results from PIVOT-02. Eur Urol. 2022; 82(4):365-373. DOI: 10.1016/j.eururo.2022.05.002. View

Pichler R, Fritz J, Zavadil C, Schafer G, Culig Z, Brunner A . Tumor-infiltrating immune cell subpopulations influence the oncologic outcome after intravesical Bacillus Calmette-Guérin therapy in bladder cancer. Oncotarget. 2016; 7(26):39916-39930. PMC: 5129981. DOI: 10.18632/oncotarget.9537. View

Powles T, Park S, Caserta C, Valderrama B, Gurney H, Ullen A . Avelumab First-Line Maintenance for Advanced Urothelial Carcinoma: Results From the JAVELIN Bladder 100 Trial After ≥2 Years of Follow-Up. J Clin Oncol. 2023; 41(19):3486-3492. PMC: 10306435. DOI: 10.1200/JCO.22.01792. View

10.

Kwon W, Lee S, Jeong T, Kim H, Lee M . Antibody-Drug Conjugates in Urothelial Cancer: From Scientific Rationale to Clinical Development. Cancers (Basel). 2024; 16(13). PMC: 11240765. DOI: 10.3390/cancers16132420. View

11.

Oddens J, Brausi M, Sylvester R, Bono A, van de Beek C, van Andel G . Final results of an EORTC-GU cancers group randomized study of maintenance bacillus Calmette-Guérin in intermediate- and high-risk Ta, T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus 3 years of.... Eur Urol. 2012; 63(3):462-72. DOI: 10.1016/j.eururo.2012.10.039. View

12.

Shore N, Boorjian S, Canter D, Ogan K, Karsh L, Downs T . Intravesical rAd-IFNα/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study. J Clin Oncol. 2017; 35(30):3410-3416. PMC: 5648171. DOI: 10.1200/JCO.2017.72.3064. View

13.

Sylvester R, Brausi M, Kirkels W, Hoeltl W, da Silva F, Powell P . Long-term efficacy results of EORTC genito-urinary group randomized phase 3 study 30911 comparing intravesical instillations of epirubicin, bacillus Calmette-Guérin, and bacillus Calmette-Guérin plus isoniazid in patients with intermediate- and.... Eur Urol. 2009; 57(5):766-73. PMC: 2889174. DOI: 10.1016/j.eururo.2009.12.024. View

14.

. Adjuvant Chemotherapy for Muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis of Individual Participant Data from Randomised Controlled Trials. Eur Urol. 2021; 81(1):50-61. PMC: 8708165. DOI: 10.1016/j.eururo.2021.09.028. View

15.

Saint F, Kurth N, Maille P, Vordos D, Hoznek A, Soyeux P . Urinary IL-2 assay for monitoring intravesical bacillus Calmette-Guérin response of superficial bladder cancer during induction course and maintenance therapy. Int J Cancer. 2003; 107(3):434-40. DOI: 10.1002/ijc.11352. View

16.

Kohut-Jackson A, Orf J, Barresi D, Davaro F, Hamilton Z . Age related trends in the utilization of neoadjuvant chemotherapy for muscle invasive bladder cancer. Urol Oncol. 2024; 42(5):160.e25-160.e31. DOI: 10.1016/j.urolonc.2024.01.006. View

17.

Li D, Yu Q, Wu R, Wang J, Feng D, Deng S . Efficiency of transurethral en-bloc resection vs. conventional transurethral resection for non-muscle-invasive bladder cancer: An umbrella review. Cancer Med. 2024; 13(11):e7323. PMC: 11141332. DOI: 10.1002/cam4.7323. View

18.

Tassinari E, Mollica V, Nuvola G, Marchetti A, Rosellini M, Massari F . Treatment Options for Metastatic Urothelial Carcinoma After First-Line Chemotherapy. Cancer Manag Res. 2022; 14:1945-1960. PMC: 9205436. DOI: 10.2147/CMAR.S287904. View

19.

Bray F, Laversanne M, Sung H, Ferlay J, Siegel R, Soerjomataram I . Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024; 74(3):229-263. DOI: 10.3322/caac.21834. View

20.

van Dijk N, Gil-Jimenez A, Silina K, Hendricksen K, Smit L, de Feijter J . Preoperative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer: the NABUCCO trial. Nat Med. 2020; 26(12):1839-1844. DOI: 10.1038/s41591-020-1085-z. View