Cytology-stratified evaluation of carcinoma in situ detection using 5-aminolevulinic acid-based photodynamic diagnosis.

BACKGROUND

Urinary cytology and white-light (WL) cystoscopy are standard tools for diagnosing bladder cancer; however, their sensitivity is limited for flat, visually inconspicuous lesions such as carcinoma in situ (CIS). Photodynamic diagnosis (PDD) using 5-aminolevulinic acid (ALA) enhances tumor visualization; however, few studies have specifically evaluated CIS detection sensitivity stratified by cytology grade.

OBJECTIVE

To evaluate the diagnostic accuracy of ALA-based PDD during transurethral resection of bladder tumors (TURBT) for detecting CIS, with cytology-stratified analyses and by anatomical site.

METHODS

We retrospectively analyzed 89 patients with histologically confirmed CIS who underwent PDD-assisted TURBT at Kochi Medical School between 2018 and 2025. Detection rates at both lesion and patient levels using WL and PDD were compared using McNemar's test. Preoperative urinary cytology was classified according to the Papanicolaou system (classes I-V).

RESULTS

In total, 217 CIS lesions were analyzed. Detection rates increased from 53.5% with WL to 87.1% with PDD (p < 0.001), with no WL-positive/PDD-negative lesions observed. PDD markedly improved detection across all subsites, particularly at the bladder neck (+56%) and dome (+37%). Overall, 31.5% of patients had at least one WL-negative/PDD-positive lesion and no WL-negative/PDD-negative lesions (true PDD-benefit), with corresponding proportions of 31.3%, 42.9%, and 24.4% for cytology classes I-II, III, and IV-V, respectively. The incremental benefit of PDD was evident across cytology strata, including cytology-negative (classes I-II) and equivocal (class III) patients.

CONCLUSIONS

ALA-based PDD-assisted TURBT significantly improves CIS detection compared with WL cystoscopy, providing consistent benefits across anatomical sites and cytologic strata.