Based on recent developments with blue light cystoscopy, the use of white light cystoscopy alone is now considered suboptimal as a diagnostic tool.
While white light cystoscopy (WLC) has been the standard for initial diagnosis and surveillance of nonmuscle-invasive bladder cancer, its use alone can now be considered suboptimal based on recent developments with blue light cystoscopy (BLC), according to Badrinath Konety, MD, MBA.
“White light cystoscopy misses many tumors, both papillary lesions and carcinoma in situ (CIS), and that can lead to higher rates of recurrence and progression,” said Dr. Konety, professor and chair of the department of urology, University of Minnesota, Minneapolis.
“Those issues are now remediable to some extent with BLC using hexaminolevulinate HCl (HAL [Cysview]) because this technique detects more tumors and allows for more complete resection.”
Fluorescent cystoscopy performed with blue light following intravesical instillation of a photoactive porphyrin provides better diagnostic accuracy by improving tumor visualization. Photoactive porphyrins selectively accumulate in neoplastic cells and lead to the accumulation of protoporphyrin IX that fluoresces with a red appearance when illuminated with blue light.
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As initially performed using 5-aminolevulinic acid, fluorescent cystoscopy demonstrated better diagnostic accuracy than WLC, but was associated with allergic reactions and systemic photosensitivity that limited its clinical utility.
The safety issues associated with 5-aminolevulinic have been overcome with the advent of HAL, Dr. Konety said.
Results from two U.S. randomized controlled trials showing that rigid BLC with HAL increased the number of papillary tumors detected compared with WLC led to the initial FDA approval of BLC with a rigid cystoscope system (Karl Storz D-Light C Photodynamic Diagnostic system) to be used as an adjunct to WLC to detect nonmuscle-invasive papillary cancer of the bladder in patients suspected or known to have lesion(s) on the basis of a prior cystoscopy.1,2 Consistent with other studies, the pivotal trials showed that BLC with HAL increased the rate of papillary tumor detection by about 20%, Dr. Konety said.
“Although increasing the number of papillary tumors found in a patient may not necessarily lead to a change in treatment, it does allow for a more thorough resection and has been shown to reduce recurrences,” he noted.
Data showing that BLC improved the detection of CIS are of greater clinical relevance, said Dr. Konety.
“Detection of previously unidentified CIS may convert the diagnosis from no cancer to cancer, and the finding of CIS in a patient with a papillary tumor may change the risk categorization and therefore the approach to treatment and surveillance,” he explained.
With its initial approval, BLC had limitations because it was approved as a one-time only procedure done with one particular type of rigid cystoscope and for finding papillary tumors. In addition, a history of BCG immunotherapy or intravesical chemotherapy within the past 90 days was a contraindication to the procedure due to concern about a potential increased risk of false positives from misidentifying inflamed tissue as cancer.
Labeling for BLC with HAL was revised and expanded based on the results of a randomized controlled trial comparing blue light flexible cystoscopy with WLC for detection of bladder cancer during surveillance.3 In February 2018, the FDA approved use of HAL for the cystoscopic detection of carcinoma of the bladder, including CIS, with flexible cystoscopy (Karl Storz PDD Flexible Blue Light Videoscope System) and for repeated examination in patients undergoing surveillance cystoscopy. In addition, the new labeling removed the contraindication relating to recent BCG or immunotherapy.
The safety of repeat use of BLC with HAL was also demonstrated in a retrospective study that included 62 patients who underwent WLC with BLC two or more times.4
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With its new labeling, BLC can now be used in the office to achieve higher specificity and sensitivity in finding bladder tumors, especially CIS, said Dr. Konety.
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“Use of BLC either in the office or the OR setting does add preparatory time,” he added, “and requires additional nursing training for catheterization and instillation of the HAL solution. It also requires purchase of specific cystoscopic equipment.”
Importantly, findings from an unpublished analysis of registry data undertaken by Dr. Konety and colleagues show that detection rates along with false-negative and false-positive rates for rigid BLC procedures performed in the community are consistent with those reported in the clinical trials.
“These findings support the idea that BLC is easy to deploy and that urologists can expect a short learning curve,” Dr. Konety said.
Narrow-band imaging (NBI) also aims to improve detection of bladder cancer and is both easy to perform and widely used. However, results from comparative studies do not show a consistent benefit for achieving improved tumor detection using narrow-band imaging versus white light cystoscopy, Dr, Konety noted.
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“Results of a very large randomized trial comparing 12-month recurrence rates following transurethral resection of bladder tumor using NBI or white light indicate that NBI did not lead to a more complete transurethral resection,” he said, referring to a European Urology study published in 2016.5
“Hence, it is unclear if NBI truly improves upon WLC,” Dr. Konety added.
Disclosures: Dr. Konety is a clinical trial investigator for Photocure, Genomic Health, Genentech, Bristol-Myers Squibb, FKD Therapies, and Spectrum Pharmaceuticals and a consultant to NxThera and MDx Health.
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1. Grossman HB, Gomella L, Fradet Y, et al. A phase III, multicenter comparison of hexaminolevulinate fluorescence cystoscopy and white light cystoscopy for the detection of superficial papillary lesions in patients with bladder cancer. J Urol 2007; 178:62–7.
2. Fradet Y, Grossman HB, Gomella L, et al. A comparison of hexaminolevulinate fluorescence cystoscopy and white light cystoscopy for the detection of carcinoma in situ in patients with bladder cancer: a phase III, multicenter study. J Urol 2007; 178:68–73.
3. Daneshmand S, Patel S, Lotan Y, et al. Flexible Blue Light Study Group Collaborators. Efficacy and safety of blue light flexible cystoscopy with hexaminolevulinate in the surveillance of bladder cancer: a phase III, comparative, multicenter study. J Urol 2017; Dec 2 [Epub ahead of print].
4. Lane GI, Downs TM, Soubra A, et al. Tolerability of repeat use of blue light cystoscopy with hexaminolevulinate for patients with urothelial cell carcinoma. J Urol 2017; 197(3 Pt 1):596-601.
5. Naito S, Algaba F, Babjuk M, et al. CROES Narrow Band Imaging Global Study Group. The Clinical Research Office of the Endourological Society (CROES) multicentre randomised trial of narrow band imaging-assisted transurethral resection of bladder tumour (TURBT) versus conventional white light imaging-assisted TURBT in primary non-muscle-invasive bladder cancer patients: trial protocol and 1-year results. Eur Urol 2016; 70:506-15.
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