The European Association of Urology (EAU) guidelines recommend upfront radical cystectomy (RC) for very high-risk (VHR) non-muscle-invasive bladder cancer (NMIBC). However, real-world adoption is limited, as most patients are reluctant to undergo immediate bladder removal. The EAU 2021 risk model set a five-year progression threshold of 20% as the decision point for RC, with a subset estimated to face a 44% progression risk. Yet, this figure was derived from BCG-naïve cohorts and may not reflect outcomes in contemporary practice. Several retrospective studies have challenged the universal role of upfront RC. Kamat et al, reported a five-year progression rate of only 14.9% among adequately BCG-treated VHR patients, with reduced model accuracy in this group. Contieri et al. found no survival difference between RC and BCG, while Miyake et al. observed a five-year progression-free survival of 79% in Japanese patients, regardless of VHR subclassification. Similarly, Subiela et al. demonstrated favourable outcomes with BCG, particularly in early responders, while Scilipoti et al. confirmed comparable survival between BCG and RC after adjustment. Importantly, delayed RC after progression was associated with inferior outcomes, emphasising the need for timely identification of BCG non-responders. The BRAVO feasibility trial highlighted the difficulty of generating level one evidence, as patient reluctance limited randomisation between RC and BCG. Current data suggest that while a subset may benefit from upfront RC, routine use risks overtreatment. Instead, individualised selection is critical, especially since adverse features such as variant histology or lymphovascular invasion have shown limited predictive value. Emerging approaches, such as urine-derived tumour DNA and molecular subtyping, offer promise in refining risk stratification. Concurrently, novel bladder-preserving strategies, including combinations of BCG with immune checkpoint inhibitors or sustained-release chemotherapy systems, are under investigation. Until validated, treatment decisions for VHR NMIBC should remain personalised, balancing oncologic risk with quality of life.
Management dilemma for very high-risk non–muscle-invasive bladder cancer
Reviewed by Asif H Ansari
Management Dilemma for very high-risk non-muscle-invasive bladder cancer: real-world data challenge the guideline recommendation for upfront radical cystectomy.
