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. 2021 Jan 28;11(2):185.
doi: 10.3390/diagnostics11020185.

Photodynamic Diagnosis-Assisted Transurethral Resection Using Oral 5-Aminolevulinic Acid Decreases the Risk of Repeated Recurrence in Non-Muscle-Invasive Bladder Cancer: A Cumulative Incidence Analysis by the Person-Time Method

Makito Miyake  1 , Nobutaka Nishimura  1 , Yasushi Nakai  1 , Tomomi Fujii  2 , Takuya Owari  1 , Shunta Hori  1 , Yosuke Morizawa  1 , Daisuke Gotoh  1 , Satoshi Anai  1 , Kazumasa Torimoto  1 , Nobumichi Tanaka  3 , Yoshihiko Hirao  4 , Kiyohide Fujimoto  1
Affiliations

Photodynamic Diagnosis-Assisted Transurethral Resection Using Oral 5-Aminolevulinic Acid Decreases the Risk of Repeated Recurrence in Non-Muscle-Invasive Bladder Cancer: A Cumulative Incidence Analysis by the Person-Time Method

Makito Miyake et al. Diagnostics (Basel). .

Abstract

Clinical evidence regarding risk reduction of repeated bladder recurrence after initial photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) is still limited in patients with non-muscle-invasive bladder cancer (NMIBC). We analyzed patients with primary NMIBC undergoing TURBT without any adjuvant treatment to compare the risk of cumulative recurrence between the conventional white-light (WL)-TURBT and PDD-TURBT. Out of 430 patients diagnosed with primary NMIBC from 2010 to 2019, 40 undergoing WL-TURBT and 60 undergoing PDD-TURBT were eligible. Multivariate Cox regression analysis for time to the first recurrence demonstrated that PDD assistance was an independent prognostic factor with better outcome (p = 0.038, hazard ratio = 0.39, and 95% confidence interval 0.16-0.95). While no patient experienced more than one recurrence within 1000 postoperative days in the PDD-TURBT group, five out of 40 patients treated by WL-TURBT experienced repeated recurrence. The comparison of cumulative incidence per 10,000 person-days between the two groups revealed that PDD assistance decreased by 6.6 recurrences per 10,000 person-days (exact p = 0.011; incidence rate ratio 0.37, Clopper-Pearson confidence interval 0.15-0.82). This is the first study addressing PDD assistance-induced risk reduction of repeated bladder recurrence using the person-time method. Our findings could support clinical decision making, especially on adjuvant therapy after TURBT.

Keywords: 5-aminolevulinic acid; bladder cancer; fluorescence; person-time method; photodynamic diagnosis; prognosis; repeated recurrence; transurethral resection; urothelial carcinoma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Representative images showing the benefit of using PDD assistance during TURBT. (A) A papillary Ta low-grade tumor is examined by both white-light (WL) and photodynamic diagnosis (PDD) modes. A small lesion (yellow arrowhead) spreads in the skirt of the tumor, which is clearly identified by PDD. (B) This lesion is equivocal on WL mode, while the PDD mode reveals a flat tumor fluorescing pink under PDD mode. The pathological examination of the biopsy confirmed that this lesion was carcinoma in situ. (C) After tumor resection, the PDD mode found a small residual tumor (yellow arrow) close to the resection margin. The additional resection was performed to achieve complete tumor resection. CIS: carcinoma in situ; TUR: transurethral resection.
Figure 2
Figure 2
Study design and flow chart of this study. NMIBC: non-muscle-invasive bladder cancer; TURBT: transurethral resection of bladder tumor; BCG: Bacillus Calmette Guérin; WL: white-light; PDD: photodynamic diagnosis.
Figure 3
Figure 3
Recurrence-free survival curves of patients treated with white-light transurethral resection of bladder tumor (WL-TURBT) or photodynamic diagnosis (PDD)-assisted (TURBT).
Figure 4
Figure 4
Swimmer’s plot of the 100 patients with time on follow-up. Individual swimmer’s plots for each patient showing the number of follow-up days for the WL-TURBT group (upper figure) and the PDD-TURBT group (lower figure). Follow-ups were performed by routine white-light cystoscopy and conventional urine cytology. Green and blue square boxes indicate low-grade and high-grade non-muscle-invasive bladder cancer (NMIBC), respectively. The red circle indicates a recurrent tumor of muscle-invasive bladder cancer (MIBC). The number of patients who experienced repeated recurrence, ranging from one to four, is shown in each figure.
See this image and copyright information in PMC

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