Comparison of Hexaminolevulinate Based Flexible and Rigid Fluorescence Cystoscopy with Rigid White Light Cystoscopy in Bladder Cancer: Results of a Prospective Phase II Study
Introduction
Bladder cancer is among the most frequent cancers in men. Superficial bladder cancer is characterized by a high recurrence rate after the initial treatment, transurethral resection with or without additional intravesical therapy. Follow up of these patients is typically done with periodic urinary cytology and cystoscopy. Although urinary markers have been studied for almost a decade now, they still lack sufficient sensitivity and specificity to apply them in clinical practice. Moreover, patients appear to have more faith in a cystoscopy than in a urinary marker analysis [1]. However, the sensitivity of cystoscopy for papillary tumours is disappointing, as was also concluded from a large EORTC meta-analysis published recently [2], [3]. The tumours that have been missed during the resection will account for at least part of the frequent recurrences after initial treatment. An even bigger problem is the diagnosis of carcinoma in situ (CIS), per definition a flat urothelial lesion. Even the use of random biopsies does not result in a clinically relevant improvement in the diagnosis of CIS [4], [5].
To improve the sensitivity of cystoscopy, especially of CIS, fluorescence cystoscopy has been studied extensively the last years [6]. Currently, the intravesical administration of new generation photo sensitizers, such as hexaminolevulinate hydrochloride (HAL), has proven to be safe and significantly improves the detection rate of papillary tumours and CIS as compared to white light cystoscopy only [7], with a clinically relevant impact on the patient's management [8]. However, all studies evaluating the value of fluorescence cystoscopy have been done with rigid cystoscopy instruments, which are typically used in the management of recurrences, transurethral resections and biopsies. Since outpatient cystoscopic follow up nowadays is predominantly done with flexible cystoscopes, and outpatient detection of CIS is also an important issue, we carried out a study to evaluate whether the technique of fluorescence cystoscopy with HAL is also feasible with a specially designed blue light flexible cystoscope.
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Material and methods
20 patients with known or suspected bladder cancer, based on outpatient cystoscopy findings or abnormal cytology, were included in a comparative within patient controlled phase II study between January and March 2004. All patients had given written informed consent. The study was conducted in accordance with Good Clinical Practice and the Declaration of Helsinki 1964, including the most recent amendment (Edinburgh, Scotland, 2000) and after written approval of the local medical ethical
Results
20 patients were included in this study, of which 3 were female. The mean age was 71 years (49–89). 10 patients had primary lesions, 7 single lesions. 7 patients had prior intravesical chemotherapy or BCG for superficial papillary tumours. 5 patients had negative cytology (all TaG2). Mean HAL instillation time was 81 min.
Of these 20 patients with suspected bladder cancer during outpatient cystoscopy, bladder cancer was histologically proven in 19. In these 19 patients 27 lesions were found. Six
Discussion
The high recurrence rate of superficial papillary bladder tumours can partly be explained by the insufficient sensitivity of cystoscopy, the golden standard in the diagnosis of bladder cancer and the lead for transurethral treatment. Although, ideally, this should be better in experienced hands, and therefore the additional value of fluorescence cystoscopy might be limited, this is unfortunately not always the case [2], [3]. In case of CIS this problem is even more prominent, since CIS is per
Conclusion
The use of HAL flexible fluorescence cystoscopy is feasible and seems to be at least comparable to results obtained with rigid white light cystoscopy, and slightly inferior to rigid fluorescence cystoscopy. HAL fluorescence cystoscopy was again confirmed to be safe. Larger studies should determine the role of flexible fluorescence cystoscopy.
Acknowledgement
This study was supported by an unrestricted educational grant from PhotoCure ASA, Oslo, Norway.
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