Counterpoint: Is stand-alone white cystoscopy a thing of the past?

April 5, 2018

More evidence is needed before blue light cystoscopy becomes the standard of care for diagnosis and treatment and renders white light cystoscopy obsolete.

Michael Risk, MD, PhD“Controversies in Urologic Cancer” is a collection of “point-counterpoint” articles in which thought leaders in the field discuss today’s key issues in prostate, bladder, and renal cancer. 

 

Although blue light cystoscopy (BLC) has demonstrated diagnostic value in bladder cancer, in detecting cancerous lesions, more evidence is needed before it becomes the standard of care for diagnosis and treatment and relegates white light cystoscopy (WLC) obsolete, according to Michael Risk, MD, PhD.

“Our specialty can be proud of the fact that there are at least 17 randomized controlled trials comparing BLC and WLC, and overall the data show that compared with WLC, BLC has greater sensitivity for tumor detection and that its use can reduce the risk of recurrence,” said Dr. Risk, assistant professor of urology, University of Minnesota, Minneapolis.

“However, the studies conducted so far have some concerning limitations, and it would be preferable to have evidence that BLC has a positive impact on more clinically meaningful endpoints. What is needed are more well-constructed randomized trials that ideally assess outcomes of progression, need for cystectomy, and survival.”

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Findings from several systematic reviews show that BLC decreases the risk of recurrence compared with WLC. The most recent study included nine trials that used hexaminolevulinate HCl (HAL [Cysview]) and six trials in which BLC was done with 5-aminolevulinic acid (not available in the United States).1

Dr. Risk said that the analyses in this paper by Chou et al showed that BLC significantly reduced the risk of recurrence at short-term (<3 months), intermediate-term (3 to <12 months), and long-term (≥12 months) follow-up.1 Data for the long-term analysis were available from 12 trials and showed a 19% relative risk reduction using BLC. A stratified analysis considering only studies of BLC with HAL also showed short-term and long-term recurrence risk was significantly reduced compared with WLC.

The authors of the paper stated, however, that the strength of the evidence favoring BLC was low.1 Inconsistency of outcomes was one concern-only two of the 12 studies included in the analysis of long-term recurrence risk found a statistically significant benefit of BLC compared with WLC.

In addition, all trials included in the Chou et al analysis were rated as having at least medium risk of bias that occurred in the form of performance and/or outcomes assessment bias. Analyses including only studies that used methodology to minimize bias showed no difference between BLC and WLC in risk of long-term recurrence.

“These data raise the question of whether the benefit of BLC was real or occurred because knowledge that the patient had BLC influenced the thoroughness of the cystoscopist’s evaluation,” Dr. Risk said.

“The findings for BLC were negative in the largest trial, but that study was only published in abstract form,” Dr. Risk said.

The largest study included 604 patients and found that groups having initial resection by BLC or WLC had nearly identical rates for both residual disease at repeat transurethral bladder tumor resection (29% vs. 29.2%) and recurrence within 2 years (18% vs 19%).2

Next: Data on more clinically meaningful endpoints are available, but limited

 

Data on more clinically meaningful endpoints are available, but limited. Only three trials included in the 2017 systematic review analyzed mortality as an endpoint, and the meta-analysis found no difference between BLC and WLC for that outcome measure. BLC also had no overall effect on progression, according to an analysis that included data from nine trials reporting progression data.1

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Although information demonstrating that BLC has a positive impact on risk of progression or mortality is desirable, Dr. Risk said that recurrence may be considered as a valid outcome measure recognizing that use of postoperative intravesical mitomycin C in the treatment of nonmuscle-invasive bladder cancer is supported by its benefit for reducing recurrence. Dr. Risk proposed, however, that it would be beneficial to also have more data to establish that BLC provides a cost benefit.

“There are published economic data supporting BLC, but those analyses also suffer from weaknesses because many are based on modeling and used effect estimates from individual studies that showed a benefit of BLC, which considering the latest systematic review, might be overestimates,” Dr. Risk said.

“More economic studies are needed, but when interpreting the data, we need to recognize that cost benefit may vary by country and even between institutions within the same country,” he said.

Looking ahead, Dr. Risk told Urology Times that FDA approval in February 2018 of flexible blue light cystoscopy with HAL and of repeated use of blue light cystoscopy with HAL opens the door to further research and the likelihood that more data on progression and mortality will be forthcoming. 

“While these approvals open up the way to greater use of BLC in the management of bladder cancer, one should keep in mind that many of the trials examined single use for TURBT, and the recent recommendation in the AUA/SUO guidelines regarding BLC is for use in TURBT, not surveillance cystoscopy3,” said Dr. Risk.

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“Repeated use can lead to detection of more cancerous lesions in follow-up.4 It remains to be seen if repeated use impacts outcomes. Until such data are available, we need to be careful that we are not simply increasing the cost of what is already the most expensive malignancy per patient.5

“The availability of good evidence on more clinically meaningful endpoints could potentially change whether BLC should become the new standard of care,” Dr. Risk said.

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References

1.  Chou R, Selph S, Buckley DI, et al. Comparative effectiveness of fluorescent versus white light cystoscopy for initial diagnosis or surveillance of bladder cancer on clinical outcomes: systematic review and meta-analysis. J Urol 2017; 197(3 Pt 1):548-58.

2.  Alken P, Siegsmund M, Gromoll-Bergmann K, et al. A randomised controlled multicenter trial to compare the effects of transurethral detection and resection of bladder carcinomas under 5-ALA induced fluorescence light to conventional white light. Eur Urol 2007; 6 (Supp):171, abstract 593.

3.  Chang SS, Boorjian SA, Chou R, et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO Guideline. J Urol 2016; 196:1021-9.

4.  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].

5.  Botteman MF, Pashos CL, Redaelli A, et al. The health economics of bladder cancer: a comprehensive review of the published literature. Pharmacoeconomics 2003; 21:1315-30.

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