Image directed redesign of bladder cancer treatment pathways: the BladderPath RCT.

Background: Transurethral resection of bladder tumour has been the mainstay of bladder cancer staging for > 60 years. Staging inaccuracies are commonplace, leading to delayed treatment of muscle-invasive bladder cancer. Multiparametric magnetic resonance imaging offers rapid, accurate and non-invasive staging of muscle-invasive bladder cancer, potentially reducing delays to radical treatment.

Objectives: To assess the feasibility and efficacy of the introducing multiparametric magnetic resonance imaging ahead of transurethral resection of bladder tumour in the staging of suspected muscle-invasive bladder cancer.

Design: Open-label, multistage randomised controlled study in three parts: feasibility, intermediate and final clinical stages. The COVID pandemic prevented completion of the final stage.

Setting: Fifteen UK hospitals.

Participants: Newly diagnosed bladder cancer patients of age ≥ 18 years.

Interventions: Participants were randomised to Pathway 1 or 2 following visual assessment of the suspicion of non-muscle-invasive bladder cancer or muscle-invasive bladder cancer at the time of outpatient cystoscopy, based upon a 5-point Likert scale: Likert 1-2 tumours considered probable non-muscle-invasive bladder cancer; Likert 3-5 possible muscle-invasive bladder cancer. In Pathway 1, all participants underwent transurethral resection of bladder tumour. In Pathway 2, probable non-muscle-invasive bladder cancer participants underwent transurethral resection of bladder tumour, and possible muscle-invasive bladder cancer participants underwent initial multiparametric magnetic resonance imaging. Subsequent therapy was determined by the treating team and could include transurethral resection of bladder tumour.

Main outcome measures: Feasibility stage: proportion with possible muscle-invasive bladder cancer randomised to Pathway 2 which correctly followed the protocol. Intermediate stage: time to correct treatment for muscle-invasive bladder cancer.

Results: Between 31 May 2018 and 31 December 2021, of 638 patients approached, 143 participants were randomised; 52.1% were deemed as possible muscle-invasive bladder cancer and 47.9% probable non-muscle-invasive bladder cancer. Feasibility stage: 36/39 [92% (95% confidence interval 79 to 98%)] muscle-invasive bladder cancer participants followed the correct treatment by pathway. Intermediate stage: median time to correct treatment was 98 (95% confidence interval 72 to 125) days for Pathway 1 versus 53 (95% confidence interval 20 to 89) days for Pathway 2 [hazard ratio 2.9 (95% confidence interval 1.0 to 8.1)], p = 0.040. Median time to correct treatment for all participants was 37 days for Pathway 1 and 25 days for Pathway 2 [hazard ratio 1.4 (95% confidence interval 0.9 to 2.0)].

Limitations: For participants who underwent chemotherapy, radiotherapy or palliation for multiparametric magnetic resonance imaging-diagnosed stage T2 or higher disease, it was impossible to conclusively know whether these were correct treatments due to the absence of histopathologically confirmed muscle invasion, this being confirmed radiologically in these cases. All patients had histological confirmation of their cancers. Due to the COVID-19 pandemic, we were unable to realise the final stage.

Conclusion: The multiparametric magnetic resonance imaging-directed pathway led to a substantial 45-day reduction in time to correct treatment for muscle-invasive bladder cancer, without detriment to non-muscle-invasive bladder cancer participants. Consideration should be given to the incorporation of multiparametric magnetic resonance imaging ahead of transurethral resection of bladder tumour into the standard pathway for all patients with suspected muscle-invasive bladder cancer. The improved decision-making accelerated time to treatment, even though many patients subsequently needed transurethral resection of bladder tumour. A proportion of patients can avoid transurethral resection of bladder tumour completely, reducing costs and morbidity, given the much lower cost of magnetic resonance imaging and biopsy compared to transurethral resection of bladder tumour.

Future work: Further work to cross-correlate with the recently developed Vesical Imaging-Reporting and Data System will improve accuracy and aid dissemination. Longer follow-up to examine the effect of the pathway on outcomes is also required. Incorporation of liquid deoxyribonucleic acid-based biomarkers may further improve the quality of decision-making and should also be investigated further.

Study registration: This study is registered as ISRCTN 35296862.

Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR135775) and is published in full in Health Technology Assessment; Vol. 28, No. 42. See the NIHR Funding and Awards website for further award information.