Effectiveness, safety and cost of fluorescence cystoscopy

Maximilian Burger is Chairman Professor of Urology and Chairman of the Department of Urology, University of Regensburg, since October 2013. He is also Fellow of the European Board of Urology, member of the bladder cancer guideline panel of the European Association of Urology (EAU), member of the bladder cancer guideline panel of the German Association of Urology (DGU) and DGU-board member.

Fluorescence cystoscopy (FC) with photosensitive agents, such as hexaminolevulinate (HAL), has demonstrated enhanced ability to visualise malignant areas, including flat or multifocal lesions that are difficult to detect using WLC, thereby resulting in more complete resections and reduced recurrence rates.2,3 Many clinical trials, including registration trials, meta-analyses and systematic reviews confirm these benefits of HAL-FC as an adjunct to WLC in clinical practice.2,4–13 One meta-analysis of prospective trials involving a total of 1,345 patients showed that, in comparison with WLC, HAL-FC significantly improved tumour detection and significantly reduced recurrence rates at 12 months, independently of patient’s risk category and whether HAL was used at initial presentation or on recurrence.2 Furthermore, a retrospective analysis showed that HAL-FC can significantly improve recurrence-free survival and overall survival in patients undergoing TURB and subsequent radical cystectomy.14 The said benefits seem pronounced in high risk NMIBC15.

HAL-FC can also improve disease staging, resulting in more appropriate treatment selection, such as adjuvant chemo- or immunotherapy or early cystectomy.1 In a phase III study, 22% of patients with confirmed NMIBC had a change of treatment after HAL-FC compared with WLC (p<0.001).9

Use of FC in the diagnosis of bladder cancer is recommended by the European Association of Urology (EAU),15 the International Consultation on Urological Diseases (ICUD)16 and the National Institute for Health and Care Excellence (NICE).17 The 2015 EAU guidelines and the second ICUD-EAU report recommend FC to guide initial TURB and biopsy and to aid diagnosis of carcinoma in situ (CIS).15,16 ICUD-EAU guidelines also recommend FC for patients with positive urine cytology but negative WLC.16 Numerous expert groups have addressed best-practice implementation of HAL-FC into clinical management of patients with NMIBC (Table 1).18–20

In addition to improving patient outcomes, HAL-FC has been shown to realise both short- and long-term cost effectiveness, despite the initial cost of equipment.21–25 Results from a UK analysis suggest that, compared with WLC alone, adjunctive HAL-FC would be expected to result in 0.060 incremental quality-adjusted life years (QALYs) and a cost saving per patient of £391 (€516) due to fewer recurrences and recurrence-associated procedures.23 A German analysis reported cost savings with FC compared with WLC to be €168 per patient per year over a median follow up of 7.1 years.24 In an Italian analysis, use of HAL-FC improved the completeness of lesion resection and tumour staging, leading to a lower recurrence rate and fewer associated TURBs and hospitalisations, compared with WLC. The incremental cost saving was €435. For the incremental cost-effectiveness ratio, HAL-FC was dominant, compared with WLC, as a result of increased QALYs and lower costs over the short term. HAL-FC remained the dominant strategy in univariate sensitivity analyses, in which the key drivers of the model included the cost of HAL-FC, the cost of WLC-assisted TURB and relative risk of recurrence. In probabilistic sensitivity analyses, HAL-FC was expected to be dominant in 92% of iterations (Table 2).25

In conclusion, incorporation of HAL-FC as an adjunct to WLC into the routine management of patients with NMIBC should be considered, given the significant benefits in detecting lesions, thus reducing recurrence rates and providing both short- and long-term cost savings.

Funding/Support and role of the sponsor: Ipsen SA provided financial support for editorial assistance in manuscript preparation. The author retained editorial control over the content.

References can be obtained from the author.
Contact: mburger@caritasstjosef.de, maximilian.burger@ukr.de

References
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17.12.2015

• bladder (21)
• management (217)