Time to Turn on the Blue Lights: A Systematic Review and Meta-analysis of Photodynamic Diagnosis for Bladder Cancer

Context: White light (WL) cystoscopy and transurethral resection of bladder tumour (TURBT) comprise the current gold standard technique for detecting and grading bladder cancer. However, with WL cystoscopy, recurrence following initial TURBT is high, and identification of smaller tumours and carcinoma in situ is poor. Photodynamic diagnosis (PDD) has been developed to improve the detection of bladder. Objective: To assess the effect of PDD-guided TURBT compared with WL on recurrence rates (RRs) in non–muscle-invasive bladder cancer (NMIBC). Evidence acquisition: A systematic review of the literature from inception to April 2020 using Medline, EMBASE, and CENTRAL was undertaken. Randomised control trials comparing TURBT undertaken with PDD to WL that reported RRs of at least 12 mo were included in the analysis. The primary outcomes were RRs at 12 and 24 mo. The secondary outcomes were reported adverse effects. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of the evidence. Evidence synthesis: Twelve randomised controlled trials (2288 patients) were included for the meta-analysis. PDD was found to reduce RRs at 12 mo (RR 0.73, confidence interval [CI] 0.60–0.88) and 24 mo (RR 0.75, CI 0.62–0.91). There was an increased risk of recurrence for patients undergoing WL at 12 mo (hazard ratio [HR] 1.14, CI 1.05–1.23) and 24 mo (HR 1.25, CI 1.15–1.35). Two studies reported recurrence data at 60 mo showing statistically significant outcomes in favour of PDD: one showed lower RRs for PDD (49% PDD vs 68% WL), whilst the other showed increased recurrence-free survival (68.2% PDD vs 57.3% WL). Adverse effects appeared to be minimal, though poorly reported. A GRADE analysis showed the evidence to be of moderate certainty overall. Conclusions: This systematic review found that PDD reduced RRs and improved recurrence-free survival compared with WL in NMIBC over at least 2-yr follow-up. These effects may persist up to 5 yr. Further research in a pragmatic study looking at longer-term outcomes beyond 24 mo will help guide recommendations on clinical adoption. Patient summary: This review suggests that photodynamic diagnosis, compared with white light cystoscopy, improves recurrence-free survival in non–muscle-invasive bladder cancer over at least 2 yr of follow-up. However, confirmatory pragmatic studies with longer-term outcomes are required for its clinical adoption.