Bladder cancer care is entering a molecular era in which the most important question may no longer be only where a tumour is located, but what biological instructions are driving it. A new consensus article from the International Bladder Cancer Group argues that clinically actionable biomarkers should be integrated into routine management rather than treated as optional tests reserved for advanced disease or specialist centres. The recommendations, published in Nature Reviews Urology, describe how molecular information can help guide diagnosis, predict treatment response and identify patients who may benefit from targeted medicines or immunotherapy.
Bladder cancer is not a single disease. Tumours that appear similar under a microscope can behave very differently, relapse at different rates and respond to entirely different treatments. Urothelial carcinoma, the most common form, is shaped by a complex mixture of genetic alterations, immune activity and changes in the tumour environment. Traditional clinical factors—such as tumour stage, grade, recurrence history and lymph-node involvement—remain essential, but they cannot fully explain this biological diversity. Biomarker testing offers a way to add that missing layer of information.
The group’s central message is that testing must be connected to a clinical decision. A biomarker is “actionable” when its result can influence treatment, surveillance or eligibility for a clinical trial. In bladder cancer, this may include alterations in the fibroblast growth factor receptor pathway, especially FGFR3, which can make some advanced tumours susceptible to FGFR-directed therapy. Other potentially relevant markers include programmed death-ligand 1, or PD-L1, which can help inform the use of immune checkpoint inhibitors in selected settings, as well as DNA repair defects, microsatellite instability and mismatch-repair deficiency, all of which may indicate an unusual sensitivity to immunotherapy.
The recommendations also highlight the importance of assessing HER2 biology, an area that has become increasingly relevant as antibody–drug conjugates and other targeted approaches expand. HER2 testing is not simply a matter of recording whether the protein is present or absent. Different laboratory methods can measure protein expression or gene amplification, and the result may depend on the assay, scoring system and quality of the tissue sample. Such technical details can determine whether a patient is correctly identified for a treatment opportunity, making standardized pathology procedures a critical part of precision oncology.
Timing is another major issue. Molecular information may be useful at diagnosis, before surgery, after recurrence or when metastatic disease develops, but the most informative sample can change as the cancer evolves. A tumour treated with chemotherapy, radiation, immunotherapy or targeted drugs may acquire new genetic features that were not present in the original biopsy. For this reason, the group supports a dynamic approach in which previously collected tissue is used when appropriate, while fresh tumour material—or, in selected circumstances, circulating tumour DNA from a blood sample—is considered when the disease changes.
This evolving biology creates a practical challenge for clinicians. A negative result from an old biopsy does not necessarily mean that a target is absent from a later tumour, just as a positive result may not guarantee that a treatment will work. Biomarkers are probabilities, not biological promises. Their interpretation must be combined with disease stage, previous therapies, organ function, patient preferences and the strength of evidence supporting a particular drug. The recommendations therefore emphasize multidisciplinary decision-making involving urologists, medical oncologists, pathologists, radiologists and molecular specialists.
The article also addresses the risk of fragmented testing. In many health systems, biomarker analysis is performed only after a patient has progressed through several lines of therapy, by which time an important treatment window may have passed. Tests may also be ordered inconsistently, interpreted using different criteria or delayed by limited access to specialized laboratories. The International Bladder Cancer Group calls for clearer testing pathways, validated assays and reporting systems that explain not only the molecular finding but also its clinical meaning, the available treatment options and the level of evidence behind them.
For patients, the shift could transform conversations about treatment. Instead of receiving a broadly defined diagnosis followed by a standard sequence of therapies, some individuals may be offered a strategy tailored to the molecular vulnerabilities of their cancer. A person whose tumour contains an actionable FGFR3 alteration, for example, may be considered for a pathway-specific drug, while another patient with immune-related biomarkers could be evaluated for checkpoint blockade. Those without an established target may be directed toward trials testing new combinations, novel antibody–drug conjugates or strategies designed to overcome resistance.
Yet precision medicine will not succeed through testing alone. The group stresses that biomarkers must be clinically validated, accessible and used equitably. Many promising molecular signals have not produced reliable benefits in large trials, and some tests remain too expensive or technically demanding for routine use. There is also a danger that unequal access to genomic profiling will widen existing differences in cancer outcomes. Integrating biomarkers into care therefore requires investment in laboratory quality, data interpretation, clinician education and reimbursement, alongside transparent communication with patients.
The wider significance of the recommendations reaches beyond bladder cancer. They represent a blueprint for moving from a one-size-fits-most model toward treatment decisions that reflect the biological identity of each tumour. As more targeted therapies and immunotherapies enter the clinic, the value of a biomarker will depend increasingly on how rapidly and accurately it can connect a patient to the right option. The International Bladder Cancer Group’s message is clear: molecular testing should not be an afterthought in bladder cancer care. It should become part of the clinical infrastructure that links diagnosis, treatment selection and the next generation of research.
Subject of Research: Bladder cancer biomarkers and their integration into clinical diagnosis, treatment selection, surveillance and precision oncology.
Article Title: Integrating clinically actionable biomarkers into bladder cancer care — recommendations from the International Bladder Cancer Group
Article References: Hensley, P.J., Teoh, J.Y.C., Li, R. et al. Integrating clinically actionable biomarkers into bladder cancer care — recommendations from the International Bladder Cancer Group. Nat Rev Urol (2026). https://doi.org/10.1038/s41585-026-01179-y
Image Credits: AI Generated
DOI: 10.1038/s41585-026-01179-y
Keywords: bladder cancer, urothelial carcinoma, biomarkers, precision oncology, FGFR3, HER2, PD-L1, immunotherapy, targeted therapy, molecular testing, circulating tumour DNA, cancer care.
