Keiji Inoue1, Hideyasu Matsuyama2, Kiyohide Fujimoto3, Yoshihiko Hirao3, Hironobu Watanabe4, Seiichiro Ozono5, Masafumi Oyama6, Munehisa Ueno6, Yoshiki Sugimura7, Hiroaki Shiina8, Hiromitsu Mimata9, Haruhito Azuma10, Yasushi Nagase11, Akio Matsubara12, Yoichi M Ito13, Taro Shuin14. 1. Department of Urology, Kochi Medical School, Kohasu, Oko, Nankoku, Kochi 783-8505, Japan. Electronic address: keiji@kochi-u.ac.jp. 2. Department of Urology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan. 3. Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. 4. Division of Urology, National Hospital Organizarion Kochi Hospital, 1-2-25 Asakuranishimachi, Kochi 780-8077, Japan. 5. Department of Urology, Hamamatsu University School of Medicine, 1-20-1 Higashi-ku, Handayama, Hamamatsu, Shizuoka 431-3192, Japan. 6. Department of UroOncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama 350-1298, Japan. 7. Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine Institute of Medical Science, 2-174 Edobashi Tsu, Mie 514-8507, Japan. 8. Department of Urology, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan. 9. Department of Urology, Oita University Faculty of Medicine, Graduate School of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan. 10. Department of Urology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686, Japan. 11. Division of Urology, Tokyo Metropolitan Tama Medical Center, 2-8-29 Musashidai, Fuchu-shi, Tokyo 183-8524, Japan. 12. Department of Urology, Hiroshima University Faculty of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. 13. Department of Biostatistics, Hokkaido University Graduate School of Medicine, North-15, West-7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan. 14. Department of Urology, Kochi Medical School, Kohasu, Oko, Nankoku, Kochi 783-8505, Japan.
Abstract
OBJECTIVE: To examine the utility and safety of photodynamic diagnosis (PDD) after oral administration of 5-aminolevulinic acid (5-ALA) (ALA-PDD) of non-muscle-invasive bladder cancer (NMIBC) using fluorescent-light (FL)-cystoscopy. METHODS: The study was a single-arm, open-label, multi-center prospective study on ALA-PDD of NMIBC, with safety as the primary endpoint and efficacy as the secondary endpoint. Diagnostic potential was evaluated through comparisons with the conventional diagnostic method using a white-light (WL)-source. Clinically recommended doses were also examined. Oral administration of 5-ALA (1.0g/50mL) was performed 180-240min before FL-cystoscopy, and positive or negative results were judged using a WL-source and based on presence or absence of red fluorescence on exposure to a blue FL-source. RESULTS: Regarding safety, the adverse drug reactions were observed as grade 1 pruritus in 1 patient (0.6%). As for efficacy, specificity and positive predictability were lower than those of a WL-source, but sensitivity was higher with a FL-source than with a WL-source. The proportion of patients with tumors detected only by FL-cystoscopy was greater than the proportion of patients with tumors detected only by conventional WL-cystoscopy. Moreover, not only sensitivity, but also the proportion of patients with tumors detected only by FL-cystoscopy, was highest among patients who received 5-ALA at ≧20mg/kg/body. CONCLUSIONS: ALA-PDD was shown to be safe and effective. Furthermore, diagnostic accuracy of PDD increased with increased dose of 5-ALA, and the recommended dose was determined as ≧20mg/kg/body in the present study.
OBJECTIVE: To examine the utility and safety of photodynamic diagnosis (PDD) after oral administration of 5-aminolevulinic acid (5-ALA) (ALA-PDD) of non-muscle-invasive bladder cancer (NMIBC) using fluorescent-light (FL)-cystoscopy. METHODS: The study was a single-arm, open-label, multi-center prospective study on ALA-PDD of NMIBC, with safety as the primary endpoint and efficacy as the secondary endpoint. Diagnostic potential was evaluated through comparisons with the conventional diagnostic method using a white-light (WL)-source. Clinically recommended doses were also examined. Oral administration of 5-ALA (1.0g/50mL) was performed 180-240min before FL-cystoscopy, and positive or negative results were judged using a WL-source and based on presence or absence of red fluorescence on exposure to a blue FL-source. RESULTS: Regarding safety, the adverse drug reactions were observed as grade 1 pruritus in 1 patient (0.6%). As for efficacy, specificity and positive predictability were lower than those of a WL-source, but sensitivity was higher with a FL-source than with a WL-source. The proportion of patients with tumors detected only by FL-cystoscopy was greater than the proportion of patients with tumors detected only by conventional WL-cystoscopy. Moreover, not only sensitivity, but also the proportion of patients with tumors detected only by FL-cystoscopy, was highest among patients who received 5-ALA at ≧20mg/kg/body. CONCLUSIONS:ALA-PDD was shown to be safe and effective. Furthermore, diagnostic accuracy of PDD increased with increased dose of 5-ALA, and the recommended dose was determined as ≧20mg/kg/body in the present study.
Keywords:
5-Aminolevulinic acid (5-ALA); Carcinoma in situ (CIS); Non-muscle invasive bladder cancer (NMIBC); Photodynamic diagnosis (PDD); The advanced medical technology
Authors: Marcel A Kamp; Igor Fischer; Julia Bühner; Bernd Turowski; Jan Frederick Cornelius; Hans-Jakob Steiger; Marion Rapp; Philipp J Slotty; Michael Sabel Journal: Oncotarget Date: 2016-10-11