Low-grade non-muscle-invasive bladder cancer: molecular landscape, treatment strategies and emerging therapies
- PMID: 40931081
- DOI: 10.1038/s41585-025-01072-0
Low-grade non-muscle-invasive bladder cancer: molecular landscape, treatment strategies and emerging therapies
Abstract
Low-grade non-muscle invasive bladder cancer is a specific category of bladder cancer with a favourable prognosis; however, its management presents several challenges. The risk of stage progression is very low, but approximately half of patients will experience recurrence within the first 5 years after diagnosis. This high propensity for recurrence, coupled with the threat of progression, mandates ongoing surveillance. However, the optimal frequency and duration of follow-up monitoring remain undefined. Current management strategies for low-grade non-muscle invasive bladder cancer rely heavily on routine office cystoscopy, with few advances in diagnostic and treatment options over the past 25 years. Our basic understanding of disease biology has substantially advanced. However, at present, considerable variations in clinical practice exist, with implications for increased financial and treatment burden for patients and health care systems. Molecular signatures and biomarker discoveries are crucial to understand disease behaviour and inform novel treatment strategies. Emerging therapies, such as advanced drug-delivery systems, immunomodulatory agents and targeted therapies, offer the potential to improve patient outcomes, streamline management and reduce the need for surveillance cystoscopies. Actionable avenues for future research in the field include prospective validation of novel biomarkers and therapies with the ultimate aim of optimizing patient care and reducing health care costs.
© 2025. Springer Nature Limited.
Conflict of interest statement
Competing interests: S.P.L declares patent: TCGA classifier; clinical trials: Aura Bioscience, FKD, JBL (SWOG), Merck (Alliance), QED Therapeutics, Surge Therapeutics; advisory board/consulting fee: Aura Bioscience, Astra Zeneca, BMS, Pfizer/EMD Serono, Protara, Surge Therapeutics, Immunity Bio UroGen, Verity, Gilead, FKD, Viventa; honoraria: Grand Rounds Urology, UroToday. J.J.M. declares advisory boards/consulting: Merck, AstraZeneca, Janssen, BMS, UroGen, Prokarium, Imvax, Pfizer, Seagen/Astellas, Ferring, CG Oncology, Calibr, Immunity Bio, Protara, Photocure. S.P.P. declares research funding: National Institute on Aging, Bladder Cancer Advocacy Network, PRIME Education, Inc, Janssen; guidelines committee: American Urological Association: Upper Tract Urothelial Carcinoma Guidelines 2023 and AUA Practice Guidelines Committee; advisory/consulting: Janssen (SunRise-4 Global Co-PI), Immunity Bio, Merck, CG Oncology, Pfizer; editorial boards: European Urology, Bladder Cancer; steering committees/leadership: Bladder Cancer Advocacy Network, KCCure/Kidney Cancer Association/International Kidney Cancer Society; educational company presentations given: PeerView, MedScape, UroToday. A.M.K. declares patent: CyPRIT (Anderson Cancer Center #00043705); grants/contracts: FKD Therapies, Patient-Centered Outcomes Institute (PCORI), Photocure, Seagen, EnGene, Arquer Diagnostis, SWOG; advisory board/consulting: Astellas Pharma, Atonco Pharma, Biologic Dynamics, Bristol-Myers Squibb, CG Oncology, Cystotech, Eisai, EnGene, Ferring, Genentech, Imagin Medical, ImmunityBio, Imvax, Incyte, Janssen, Medac, Merk, Nonagen Bioscience, Pfizer, Photocure, Protara Therapeutics, Roche, Seagen, Sesen Bio, Theralase, urogen Pharma, US Biotest, Valar Labs, Vivet Therapeutics; boards/committee: IBCG, European Urology Oncology, Journal of Urology, UroToday, World Bladder Cancer patient Coalition, American Urological Association. L.D. declares funding agreement: 2i Genomics, Veracyte, Natera, AstraZeneca, Photocure and Ferring; advisory/consulting: Ferring, MSD, Cystotech, AstraZeneca and UroGen; honoraria: AstraZeneca, Pfizer and Roche and travel support from MSD. R.L. declares research support: Predicine; Valar labs; Johnson & Johnson; scientific adviser/consultant: BMS, Merck, CG Oncology, ImmunityBio, Pfizer, Johnson & Johnson, AstraZeneca, enGene, Valar Labs; honoraria: UroToday, IBCG, MashUP Media, MJH Lifesciences; travel: Predicine, CG Oncology, Johnson & Johnson. P.E.S. declares vice-chair of the NCCN bladder and penile cancer panel. All other authors declare no competing interests.
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