Innovative Molecular and Therapeutic Approaches in Conservative Management of Urothelial Carcinoma

Urothelial carcinoma is a multifaceted malignancy that includes non–muscle-invasive bladder cancer (NMIBC) and upper tract urothelial carcinoma (UTUC), each displaying unique anatomical, clinical, and molecular profiles. Despite a common cellular origin, NMIBC and UTUC are now understood to be separate biological entities with distinct genetic underpinnings and microenvironmental influences. Traditionally, radical surgery has been the standard care for advanced disease, yet contemporary uro-oncology is witnessing a paradigm shift—placing greater emphasis on organ preservation to enhance quality of life and minimize treatment-related morbidity. The increasing recognition of molecular heterogeneity and emerging resistance to conventional therapies, particularly in BCG-unresponsive NMIBC, have underscored the need for novel, effective, and less invasive strategies to achieve durable disease control.

In recent years, the clinical management of both NMIBC and UTUC has been invigorated by advances in immunotherapy, innovative drug delivery systems, gene-based interventions, and minimally invasive techniques. New intravesical agents, gene therapies, and oncolytic viruses are offering hope to patients with limited options, while technological progress in endoscopy and molecular characterization is enabling the safe application of kidney- and bladder-sparing approaches in select cohorts of UTUC and NMIBC. The identification and deployment of predictive biomarkers—ranging from urinary DNA mutations to immune and transcriptomic signatures—are enhancing patient selection, optimizing treatment response, and paving the way for personalized, conservative therapy. However, challenges remain in translating these innovations into standardized care, particularly in the integration of molecular diagnostics and novel therapeutics across diverse clinical settings.

This Research Topic aims to bring together current advances and foster cross-disciplinary dialogue around conservative management of NMIBC and UTUC. We seek manuscripts elucidating the molecular basis for organ-sparing interventions, as well as studies highlighting the development and validation of new biomarkers to guide individualized therapy. Additionally, we encourage submissions that address the efficacy and safety of emerging pharmacologic, immunologic, and endoscopic treatments—especially those that bridge minimally invasive surgery with molecularly targeted modalities. By uniting translational, clinical, and technological perspectives, this Research Topic aspires to redefine the landscape of urothelial carcinoma care, aligning oncological outcomes with organ function and patient quality of life.

To gather further insights in the evolving field of conservative therapy for NMIBC and UTUC, we welcome articles addressing, but not limited to, the following themes:

- Molecular profiling and biomarker discovery for patient selection and response prediction.
- Innovations in intravesical and intracavitary therapies.
- Advances in minimally invasive surgical techniques for bladder and kidney preservation.
- Development of novel drug delivery and gene therapy platforms.
- Integration of molecular diagnostics into clinical pathways.
- Strategies for overcoming drug resistance in localized disease.
- Real-world outcomes and quality-of-life assessments of organ-sparing interventions.

Dr. Di Bello declared the following conflicts of interest:
- He has received the EAU Endourology Fellowship Grant, sponsored by COOK Medical.

Dr. Breda declared the following conflicts of interest:
- He is consultant for KARL STORZ and COOK Medical.


Please note: Manuscripts relying solely on bioinformatics or computational analyses of public genomic or transcriptomic datasets, without validation in independent cohorts or experimental models, will not be considered.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Non–muscle-invasive bladder cancer, upper tract urothelial carcinoma, bladder-sparing therapy, kidney-sparing surgery, Intravesical therapy, biomarkers, immunotherapy, targeted drug delivery, molecular oncology

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.