Poor Prognosis With Intravesical Bacillus Calmette-Guérin History After Photodynamic Diagnosis-assisted Transurethral Resection Using 5-Aminolevulinic Acid

Abstract

Background/Aim: Diagnostic efficacy and treatment outcome of orally administered 5 aminolevulinic acid (ALA) assessment for photodynamic diagnosis (PDD) in transurethral resection for non-muscle-invasive bladder cancer (NMIBC) in clinical practice. Patients and Methods: A retrospective analysis was performed of 105 patients who underwent PDD transurethral resection using orally administered ALA and were pathologically diagnosed with Ta, T1, or Tis at the Ishikawa Prefectural Central Hospital from December 2018 to May 2022. Results: Fluorescent light had a significantly higher sensitivity but a lower specificity in detecting carcinoma compared to white light (91.7% vs. 77.1%; p<0.05 and 43.0% vs. 85.2%; p<0.05, respectively), as well as in detecting carcinoma in situ lesions (80.4% vs. 28.6%; p<0.05 and 23.3% vs. 84.5%; p<0.05, respectively). The cumulative frequency of recurrence and progression 1 year after treatment were 26.3% and 12.3%, respectively. Multivariate analyses indicated that a Bacillus Calmette-Guérin (BCG) history instillation was an independent predictive factor for intravesical recurrence (hazard ratio=4.439; p=0.002) and disease progression (hazard ratio=8.534; p=0.005). The 1-year cumulative recurrence rates were 66.2% and 16.5%, respectively (p<0.001), and progression rates for patients with and without prior BCG intravesical instillation were 50.4% and 3.5%, respectively (p<0.001). Conclusion: Sufficient diagnostic accuracy and relatively good treatment outcome was shown in PDDtransurethral resection using ALA. However, prior BCG intravesical instillation for NMIBC patients was a poor prognostic factor of cancer recurrence and progression, and may be useful for clinicians in their postoperative follow-up.Transurethral resection of bladder tumor (TURBT) by intraoperative cancer detection under white light (WL) (1) is the standard therapy for non-muscle-invasive bladder cancer (NMIBC) in clinical practice, which accounts for approximately 70% of bladder cancers (BCs). However, about 50% of NMIBCs recur, and BC invades the muscle layer in the recurrence process in 15%-30% of cases (2). Therefore, improving TURBT quality and increasing the complete tumor resection rate is essential to reduce the recurrence risk. The protoporphyrin IX precursor called 5aminolevulinic acid (ALA) is attracting attention as a new generation photosensitive material for photodynamic diagnosis (PDD). PDD assisted TURBT using orally administered ALA has demonstrated clear advantages in Japan in terms of increased tumor detection and improved oncological outcome (3-7). Clinical data originating from Japan are not yet sufficient, although ALA was made available under the Japanese public medical insurance system in 2017.Recently, the Bacillus Calmette-Guérin (BCG) unresponsive disease concept was advocated; a group of diseases that recur despite adequate BCG intravesical therapy and are considered ineffective for reintroduction of BCG intravesical therapy (8, 9). However, it is unclear how prior BCG intravesical treatme...

Photodynamic Diagnosis and Therapy in Non-Muscle-Invasive Bladder Cancer

“…In the BCG combination therapy group, the presence or absence of PDD did not show a significant difference in 2-year progression-free survival, and PDD did not affect disease progression control [112]. Makino et al revealed that prior BCG infusion history, particularly BCG-unresponsive disease, is responsible for poor prognostic factors in NMIBC patients undergoing PDD-TURBT [115]. Thus, special postoperative follow-up may be needed for these patients.…”