Photodynamic versus white-light-guided resection of first-diagnosis non-muscle-invasive bladder cancer: PHOTO RCT.

backgroundAround 7500 people are diagnosed with non-muscle-invasive bladder cancer in the UK annually. Recurrence following transurethral resection of bladder tumour is common, and the intensive monitoring schedule required after initial treatment has associated costs for patients and the NHS. In photodynamic diagnosis, before transurethral resection of bladder tumour, a photosensitiser that is preferentially absorbed by tumour cells is instilled intravesically. Transurethral resection of bladder tumour is then conducted under blue light, causing the photosensitiser to fluoresce. Photodynamic diagnosis-guided transurethral resection of bladder tumour offers better diagnostic accuracy than standard white-light-guided transurethral resection of bladder tumour, potentially reducing the chance of subsequent recurrence.

objectiveThe objective was to assess the clinical effectiveness and cost-effectiveness of photodynamic diagnosis-guided transurethral resection of bladder tumour.

designThis was a multicentre, pragmatic, open-label, parallel-group, non-masked, superiority randomised controlled trial. Allocation was by remote web-based service, using a 1 : 1 ratio and a minimisation algorithm balanced by centre and sex.

settingThe setting was 22 NHS hospitals.

participantsPatients aged ≥ 16 years with a suspected first diagnosis of high-risk non-muscle-invasive bladder cancer, no contraindications to photodynamic diagnosis and written informed consent were eligible.

interventionsPhotodynamic diagnosis-guided transurethral resection of bladder tumour and standard white-light cystoscopy transurethral resection of bladder tumour.

main outcome measuresThe primary clinical outcome measure was the time to recurrence from the date of randomisation to the date of pathologically proven first recurrence (or intercurrent bladder cancer death). The primary health economic outcome was the incremental cost per quality-adjusted life-year gained at 3 years.

resultsWe enrolled 538 participants from 22 UK hospitals between 11 November 2014 and 6 February 2018. Of these, 269 were allocated to photodynamic diagnosis and 269 were allocated to white light. A total of 112 participants were excluded from the analysis because of ineligibility ( LIMITATIONS: Fewer patients than anticipated were correctly diagnosed with intermediate- to high-risk non-muscle-invasive bladder cancer before transurethral resection of bladder tumour and the ratio of intermediate- to high-risk non-muscle-invasive bladder cancer was higher than expected, reducing the number of observed recurrences and the statistical power.

conclusionsPhotodynamic diagnosis-guided transurethral resection of bladder tumour did not reduce recurrences, nor was it likely to be cost-effective compared with white light at 3 years. Photodynamic diagnosis-guided transurethral resection of bladder tumour is not supported in the management of primary intermediate- to high-risk non-muscle-invasive bladder cancer. FUTURE WORK: Further work should include the modelling of appropriate surveillance schedules and exploring predictive and prognostic biomarkers.

trial registrationThis trial is registered as ISRCTN84013636.

fundingThis project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in