Johnson & Johnson has funded the development and publication of this article, including a consultancy fee for Eva Compérat and Markus Eckstein. The views expressed in the article are those of the authors and publisher, and do not necessarily reflect the views of Johnson & Johnson. CP-545293 | October 2025.
In the past, therapeutic choices for patients with bladder cancer were limited. While patients with superficial bladder cancer often endured repeated cystoscopies and surveillance procedures, which are both burdensome and costly, those with advanced bladder cancer were usually offered only chemotherapy. Today, precision medicine advances have identified biomarkers that are driving innovation in both diagnostics and drug development for superficial and advanced stages of bladder cancer.
Advances in next-generation sequencing (NGS) have revealed distinct molecular profiles in non-muscle-invasive bladder cancer (NMIBC), muscle-invasive bladder cancer (MIBC), and both locally advanced (LA) and metastatic urothelial carcinoma (mUC) with therapeutic relevance – including FGFR, HRAS, ERBB2, PIK3CA, and TP53 (1,2). Each of these alterations may potentially correspond to unique pathogenic pathways – and be associated with varying prognoses.
Therapeutic innovations such as antibody-drug conjugates, PD-1 and FGFR inhibitors will continue to transform the treatment landscape for patients with NMIBC, MIBC, and LA/ mUC. In the metastatic setting, molecular testing is already a requirement for selecting patients eligible for targeted therapy after progression on immunotherapy.
Guidelines highlight the increasing role of biomarker-driven precision medicine
In Europe, bladder cancer testing guidelines such as those from ESMO and The European Association of Urology include (3,4):
Applying PD-L1 testing to support decision making for:
first-line therapy in patients with metastatic bladder cancer if platin ineligible
adjuvant nivolumab treatment following radical cystectomy in curative intent.
Testing for susceptible FGFR3 gene alterations in patients with mUC or unresectable tumors, ideally upon progression to first-line standard of care.
The use of HER2 overexpression status to guide treatment decisions in metastatic disease.
The importance of a multidisciplinary approach to patient care, alongside the need for shared decision-making to ensure treatment choices reflect both clinical and personal priorities of patients.
These guidelines indicate we’re at a critical point where patient needs, industry guidelines, and biomarker breakthroughs are converging for a new era of precision-based approaches in bladder cancer treatment.
The evolving precision medicine landscape
Despite significant advances in the molecular characterization of bladder cancer, many unanswered questions remain. Along with variation in how biomarkers appear and behave between patients, there are gaps in our understanding of their ability to guide care. This has led to disparities in testing protocols across the European region.
Another pressing challenge is diagnostic turnaround time. In advanced bladder cancer, patients are often under intense therapeutic pressure. Waiting two to four weeks for NGS results can be a critical delay in a disease where every week matters, especially if visceral metastases are present or the overall metastatic burden is very high.
And, while precision medicine advancements are exciting, they require clinicians to navigate an increasingly intricate landscape. This is where pathology plays a pivotal role: ensuring that the right test is performed, interpreted, and communicated so that patients receive the appropriate therapy.
Pathology: leading the way in personalized care
Pathologists play a vital role in recognizing and understanding the implications of actionable genetic mutations. Looking ahead, it will be crucial to consult pathology early in the development and implementation of personalized medicine strategies, ideally in the phase of early clinical development.
In the clinic, strong communities comprising oncologists, urologists, and pathologists advocating for fairer reimbursement, while also pooling resources – for example, by funding shared sequencing facilities – could significantly reduce the costs of genetic biomarker testing. This, in turn, would make it easier to justify testing expenses to regulatory agencies – which, overall, are much lower compared to very high drug costs.
There is also a real need to reach out to smaller hospitals and community settings, where awareness and resources may be limited. Bringing pathology expertise and education into these environments will help ensure that all patients – no matter where they are treated – benefit from advances in personalized care and can be treated according to current standard of care.
The precision medicine model is well established for patients with breast and lung cancer (5, 6), where companion diagnostics are widely understood and pathologists are frequently involved as integral parts of (molecular) tumor boards. These successes show that best practice in biomarker testing depends not only on the scientific validity of a marker, but also on how seamlessly it can be integrated into existing pathology workflows.
The route to enhanced personalized care
To improve accessibility to biomarker testing, building greater testing capacity could be the way forward. High-volume centers can process samples more efficiently, filling sequencing machines faster and reducing turnaround times compared to smaller laboratories.
At the same time, there may be value in implementing rapid, lower-cost testing modalities alongside NGS. For example, for certain biomarkers with defined variants of interest, PCR-based assays can deliver reliable results quickly.
Other questions arise around whether reflex testing should be implemented – that is, performing molecular testing automatically on every patient with advanced bladder cancer at diagnosis, rather than waiting for a clinician to request it. Though cost and workforce must be considered, reflex testing can save valuable time, allowing clinicians to initiate targeted therapy sooner.
There are also promising initiatives exploring liquid biopsy testing in some European countries. As NGS technologies become more sensitive, liquid biopsy will likely become more widely used. For now, however, it is generally viewed as a complementary tool to tissue-based testing rather than a replacement, and comes along with own limitations, such as non-ctDNA-shedding tumors.
AI-driven multi-omics and data integration approaches may significantly accelerate the identification of therapeutic vulnerabilities in cancer – greatly accelerating drug development. For this reason, education must be central to pathology’s role in precision medicine.
The bladder cancer forecast
The future of personalized care in advanced bladder cancer will require speed, collaboration, and education. By strengthening infrastructure, embracing rapid testing alongside comprehensive sequencing, and embedding pathology more deeply into multidisciplinary care, the field can move closer to delivering timely, accurate, and individualized treatment for every patient.
In short, pathology will remain the foundation of diagnosis while also leading the integration of new testing approaches. To succeed, we must combine technical rigor with ongoing education. Only then will we ensure that every patient has access to timely, personalized care, and, therefore, optimal treatment outcomes.
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References
- M Ferro et al., “Emerging biomarker in bladder cancer: translating molecular advances into precision oncology,” Crit Rev Oncol Hematol, 215 (2025). PMID: 40712901.
- L C Kompier et al., “FGFR3, HRAS, KRAS, NRAS and PIK3CA mutations in bladder cancer and their potential as biomarkers for surveillance and therapy,” PLoS One, 5, 11 (2010). PMID: 21072204.
- EAU, “EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer” (2025). Available at: https://uroweb.org/guidelines/muscle-invasive-and-metastatic-bladder-cancer.
- T Powles et al., “Bladder Cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up,” Ann Oncol, 33, 3 (2022). PMID: 34861372
- H Jeon et al., “Update 2025: Management of non-small-cell lung cancer,” Lung, 203, 1 (2025). PMID: 40133478.
- A T Jacobs et al., “Targeted therapy for breast cancer: an overview of drug classes and outcomes,” Biochem Pharmacol, 204 (2022). PMID: 35973582.
