• This study compares ALA-based PDD and white-light cystoscopy with a specific focus on CIS. • ALA-PDD improved CIS detection across all bladder subsites. • Cytology-stratified analysis showed that PDD improves CIS detection even in cytology-negative and equivocal cases. 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. 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. 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). 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. ALA-based PDD-assisted TURBT significantly improves CIS detection compared with WL cystoscopy, providing consistent benefits across anatomical sites and cytologic strata.
Shigehisa et al. (Sun,) studied this question.