78 A major review has raised the alarm over current methods used to assess progression risk in non-muscle-invasive bladder cancer (NMIBC), suggesting that existing tools fail to accurately identify patients who will develop the more dangerous form of the disease. NMIBC accounts for around 75 percent of bladder cancer cases, but up to 45 percent of these patients eventually progress to muscle-invasive disease, which carries a significantly worse prognosis. For years, clinicians have relied on risk stratification models based solely on clinical and pathological features, such as tumour size, grade, and recurrence history. However, the latest evidence shows these models are often unreliable, leading to both undertreatment and overtreatment. Researchers from the Erasmus MC Cancer Institute have now called for a shift towards incorporating molecular biomarkers to enhance how NMIBC is assessed and managed. Their review, published in Nature Reviews Urology, examines recent breakthroughs in genomic and transcriptomic profiling that reveal deeper insights into the biological mechanisms driving bladder cancer progression. Among the most promising findings are single-gene biomarkers such as CCNE1, FOXM1, and STAG2, which are implicated in cell cycle control and chromosomal stability. These genes have consistently shown strong associations with disease progression, but none has yet been prospectively validated for routine clinical use. This lack of validation remains a major barrier to their implementation. The study also explores emerging gene signatures, such as the 12-gene PCR panel and the Molecular Progression Risk Score. These multi-gene tools have demonstrated some ability to predict progression risk, yet their real-world impact remains limited without integration into current clinical workflows. Molecular subtyping has added further depth, dividing NMIBC into biologically distinct categories with varying degrees of aggressiveness. For example, the UROMOL21 classification scheme identifies a high-risk Class 2a subtype, which shows a poor prognosis and might benefit from earlier, more aggressive treatment. However, issues such as tumour heterogeneity, high costs, and long turnaround times continue to hinder practical use in most healthcare settings. The researchers emphasise that any future improvements in bladder cancer care will depend on high-quality validation studies. These studies would need to demonstrate that using biomarkers can meaningfully improve patient outcomes, not just enhance diagnostic precision. They argue that until this is achieved, molecular profiling will remain a promising but underused tool in the fight against bladder cancer. There is optimism that combining existing risk stratification models with biomarker data could lead to more personalised treatment plans, sparing some patients from invasive surgery while ensuring others receive timely intervention. Yet the path to clinical adoption remains long, and experts stress the need for coordinated international efforts to bring these scientific advances into mainstream care.