Hexaminolevulinate blue light cystoscopy improves bladder cancer detection in comparison to white light cystoscopy: a prospective, comparative, within-patient controlled multicenter phase III bridging study in China

MUxin Li^1,2Xiaoliang Yuan^3*Hailong Hu⁴Lulin Ma⁵Shudong Zhang⁵JIANMING GUO⁶Xiuheng Liu⁷Yonglian Guo⁸Jin Wen⁹Hongxian Zhang¹⁰Shuai Jiang⁵Wang He⁷Cheng Liu⁷Jian Huang¹⁰Monika Haefner¹¹Bernd-Claus Weber¹²Kristine Young-Halvorsen¹³Hanzhong Li^2*

• ¹Medsci, Beijing, China
• ²Peking Union Medical College Hospital, Beijing, China
• ³Jiangsu Yahong Meditech Co., Ltd, Room 103, 11F,New Bund World Trade Center(PhaseIII),building B No.11, Lane 221 Dongyu Road, Pudong, Shanghai, China., Jiangsu, China
• ⁴The Second Hospital of Tianjin Medical University, Tianjin, China
• ⁵Peking University Third Hospital, Beijing, China
• ⁶Zhongshan Hospital Fudan University, Shanghai, China
• ⁷Wuhan University Renmin Hospital Department of Urology, Wuhan, China
• ⁸The Central Hospital of Wuhan, Wuhan, China
• ⁹Peking Union Medical College Hospital Department of Urology, Beijing, China
• ¹⁰Sun Yat-Sen Memorial Hospital, Guangzhou, China
• ¹¹Richard Wolf GmbH, Clinical Affairs Dept., Knittlingen, Germany, Knittligen, Germany
• ¹²Richard Wolf GmbH, Knittlingen, Germany
• ¹³Photocure ASA, Clinical Development and Medical Affairs, Oslo, Norway, Oslo, Norway

Background and Objective: To compare hexaminolevulinate (HAL) blue light cystoscopy (BLC) with white light cystoscopy (WLC) in the detection of bladder cancer. Methods: Patients received intravesical HAL (Hexvix®) and underwent WLC before randomization to undergo high-definition BLC (System blue). Lesions identified in either WLC or BLC were evaluated by a blinded panel. The primary efficacy endpoint was the proportion of patients with histology-confirmed tumors (Ta, T1, or CIS) who have at least one such tumor found by BLC but not by WLC. Secondary endpoints included detection of CIS, lesion detection rates, false positive rate, and safety. Results: Of 158 (160 screened patients) enrolled patients, 120 underwent WLC and were randomized (6 WLC, 114 BLC), 97 were diagnosed with NMIBC.The mean age were 65.30±12.18 years. 11.4%(13/114) suffered from CIS, 84.6% (11/13) were detected with additional lesions by BLC, 61.5% (8/13) were diagnosed solely by BLC. Compared with WLC, the proportion of patients with additional bladder cancer lesions detected by HAL BLC was 43.3% ([33.27%, 53.75%] p < 0.0001). The proportion of patients with CIS lesions detected by HAL BLC and not by WLC was 9.6% [4.9%,16.6%]. Detection rates for CIS, Ta, T1 and T2-T4 tumors were 94.7%, 100%, 98.2% and 100% for BLC and 42.1%, 76.1%, 91.2% and 100% for WLC, respectively. The false-positive rate was 23.2% [19.2%,27.7%] and 16.0%[11.9%, 20.8%] for BLC and WLC, respectively. 95 patients (60.1%) reported 200 cases of AE, 9 AEs were drug-related (fever, bladder pain, etc.). 9 device deficiencies (5.7%) occurred (8 quality issues and 1 device failure). No AEs and SAEs leading to discontinuation. Conclusions: In the setting of modern high-definition equipment, HAL BLC significantly improves the detection of bladder cancer and with favourable safety.