Photodynamic diagnosis-assisted transurethral resection using oral 5-aminolevulinic acid decreases residual cancer and improves recurrence-free survival in patients with non-muscle-invasive bladder cancer

Background: 5-aminolevulinic acid is a protoporphyrin IX precursor used for photodynamic diagnosis. We aimed to clarify the therapeutic benefits of orally administered 5-aminolevulinic acid for photodynamic diagnosis in transurethral resection for non-muscle-invasive bladder cancer in a real-world setting.

Methods: From January 2009 to December 2020, patients with non-muscle-invasive bladder cancer who have undergone visually complete resection by initial transurethral surgery were included. Histopathologically confirmed residual and intravesical recurrent bladder cancer was retrospectively investigated and compared with transurethral resection using photodynamic diagnosis and conventional white light.

Results: One hundred and fifteen patients who underwent photodynamic diagnosis-transurethral resection were compared with 346 patients who underwent white light-transurethral resection. The second transurethral resection revealed that the proportion of residual T1 and Ta bladder cancer was lower in the photodynamic diagnosis group than in the white light group (10.3% vs. 33.8%, P = 0.001). Additionally, the proportion of intravesical recurrence was lower in the photodynamic diagnosis group than in the white light group (9.6% vs. 41.9%, P < 0.001). Using 5-aminolevulinic acid-photodynamic diagnosis during transurethral resection of bladder tumor improved the cumulative intravesical recurrence-free survival (log-rank test: P < 0.001). Furthermore, multivariate analyses indicated that not using 5-aminolevulinic acid-photodynamic diagnosis was an independent predictive factor for residual bladder cancer (odds ratio, 6.16; 95% confidence interval, 2.10-18.0; P < 0.001) and intravesical recurrence (hazard ratio, 2.01; 95% confidence interval, 1.05-3.83, P = 0.034).

Conclusions: Introducing 5-aminolevulinic acid-photodynamic diagnosis into transurethral resection reduces residual bladder cancer and improves the cumulative intravesical recurrence-free survival in patients with non-muscle-invasive bladder cancer, indicating its possible therapeutic benefits.