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BackTable / Urology / Article
Blue Light vs White Light Cystoscopy in Bladder Cancer
Javier Prieto III • Updated Oct 7, 2024 • 42 hits
The traditional approach to bladder cancer workup, using TURBT with white light cystoscopy, misses a significant number of tumors. Adding blue light cystoscopy with hexaminolevulinate enhances visualization of cancerous tissue that white light alone can't detect, improving tumor resection and reducing recurrence and malignancy. Evidence clearly delineates the usefulness of blue light cystoscopy in almost all bladder cancer cases, except for those with high-volume tumors.
Dr. Suzanne Merrill and Dr. Suzette Sutherland, pioneers in the field of urology, emphasize the importance of implementing blue light cystoscopy in almost all TURBT procedures due to its ability to improve patient outcomes. They also highlight the continued significance of white light cystoscopy, which should not be phased out. The research-backed consensus is that using both blue and white light cystoscopy together ensures peak effectiveness and reduces unnecessary resections.
This article features excerpts from the BackTable Urology Podcast. We’ve provided the highlight reel in this article, and you can listen to the full podcast below.
The BackTable Urology Brief
• Bladder cancer diagnosis during TURBT is improved by using Cysview with blue light cystoscopy, which illuminates cancerous cells missed by white light alone. By interacting with the heme biosynthesis pathway, Cysview highlights malignant areas, reducing the chances of leaving unresected cancerous tissue and improving patient outcomes.
• Blue light cystoscopy is highly effective for diagnosing carcinoma in situ (CIS) and is increasingly recommended for all bladder cancer patients, particularly during follow-up TURBTs. However, its effectiveness may be limited in high-volume tumor cases, where large tumors make it harder to distinguish between healthy and malignant tissue.
• New data shows that blue light cystoscopy is effective in detecting bladder cancer but should complement white light cystoscopy during TURBT for optimal results. While blue light enhances detection, it risks false positives in inflamed areas, so alternating both techniques ensures accurate resection.
Table of Contents
(1) The Fundamentals of Blue Light Cystoscopy in Bladder Cancer
(2) Is Blue Light Cystoscopy Suitable for All Bladder Cancer Patients?
(3) Is White Light Cystoscopy Obsolete in Modern Medicine?
The Fundamentals of Blue Light Cystoscopy in Bladder Cancer
The new standard for diagnosing bladder cancer involves performing TURBT while using both white and blue light cystoscopy along with an optical imaging agent called Cysview. Although other agents like Hexvix exist, Cysview is the most commonly used by urologists. [1]
Cysview, the brand name for hexaminolevulinate, works in conjunction with blue light cystoscopy to provide photosensitizing activity, allowing for the detection of cancer pathology within the bladder through fluorescence. [2] This agent interacts with the heme biosynthetic pathway, accumulating in photoactive porphyrins. These porphyrins tend to gather in malignant and dysplastic cells, and under blue light technology, they illuminate as bright pink, making it easier to detect at-risk areas of the bladder.
While these regions are easily identified with blue light cystoscopy, they cannot be seen with white light cystoscopy alone. Without the proper illumination provided by Cysview, poorer outcomes are likely, as pathological regions may go unresected, leading to missed carcinomas during TURBT.
[Dr. Suzette Sutherland]:
Yes. It's oh so important to really know the accurate histology, right? At the time of biopsy, at the time of look-see, right? When we take them for a look, cystoscopically, whether it's in the office or in the OR, we want to be really confident that we know what we're seeing, that when we see nothing, as an example, that we really are seeing nothing. So tell us about the blue light cystoscopy, the Cysview, how that works, and how that enhances our visualization.
[Dr. Suzanne Merrill]:
Yes. So as you mentioned, definitely the cornerstone for diagnosis is that TURBT. Use of blue light cystoscopy combined with the optical imaging agent called Cysview-- It has a long generic name or chemistry name to it, which I'm not going to even go into here. Ultimately, you put this agent into the bladder and it interacts with the heme biosynthetic pathway. It accumulates in these photoactive porphyrins.
It is these photoactive porphyrins which preferentially accumulate in malignant cells. Then when we use blue light illumination, it's these photoactive porphyrins that then, which are accumulated in the cancerous cells, fluoresce bright pink under that blue light illumination. You're able to visually see where these cancerous cells and conglomerations of these cancerous cells are, where they might not be apparent under white light.
Really where this optical imaging agent has shined, if you will, to use that is in carcinoma in situ cases. Where we know that that disease specifically can be elusive under white light, we can miss it, this agent really has shown to be uptake specifically in that superficial type of bladder cancer and allows us to visualize it, resect it, even see the margins of our resection to be able to fully resect and evacuate the cancer from the patients at the time of the TURBT.
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Is Blue Light Cystoscopy Suitable for All Bladder Cancer Patients?
Blue light cystoscopy has been well-documented to be highly effective when diagnosing bladder carcinoma in situ (CIS). One study revealed striking results, showing that when white light cystoscopy was used instead of blue light, CIS was missed in 34.6% of cases. With such compelling data, its role in CIS diagnosis is undisputed, and recent research is now highlighting its potential in broader applications.
The consensus is shifting toward blue light cystoscopy being suitable for all bladder cancer patients, regardless of tumor grade or stage. There are generally no downsides to using blue light cystoscopy during any resection. It offers particular advantages during follow-up TURBTs, where it helps confirm that all tumor tissue has been removed and that the resection margins are properly visualized. This approach has gained increased interest, especially in light of research indicating that some tumor tissue remains in the bladder after the initial TURBT in about 76% of cases.
However, blue light cystoscopy is not always recommended, especially in high-volume tumor cases. In these situations, the large tumor size overwhelms the environment, making it difficult to distinguish normal tissue, as the increased activity of the heme biosynthesis pathway leads to an accumulation of photoactive porphyrins that transilluminate most of the region, rendering the technique less useful.
[Dr. Suzette Sutherland]::
I've had the opportunity to use this myself and was really astounded at what I saw on white light versus what I then was able to see on blue light. It really was an eye-opener. The first time I used it was several years ago, but it really was an eye-opener. I'm a firm believer that it helps with diagnostics at this point and really that it should be used, if possible, on almost all patients. What are your thoughts on that? When it should be used or is there a time when it shouldn't be used?
[Dr. Suzanne Merrill]:
I think it's an important topic to bring up. It's certainly one of discussion and one of preference. I will tell you that when this optical imaging agent rolled out, it was FDA-approved in 2010. It's been around for quite some time. Initially, we were using it in patients that we knew already had a diagnosis of CIS, where it has shown to detect that cancer, actually showing ultimately that it detects it, just to give you some hard data here-- CIS tumors were found in 34.6% of patients compared to, for example, white light. The CIS tumors were only found in blue light up to 34.6% of the time.
[Dr. Suzette Sutherland]::
That's a huge number, right? One-third of the patients and we're talking about something as serious as CIS.
[Dr. Suzanne Merrill]:
Exactly. Initially, people thought, "Well, maybe I should only use it for CIS patients." Ultimately, right, we only know a patient has CIS after that first TURBT. People would use it in that sort of situation. It was also felt to be a good use in people that had that positive cytology, but that white light, surveillance cystoscopy didn't show anything abnormal. You could use it there to see if we could see anything better, under blue light luminescence.
Is White Light Cystoscopy Obsolete in Modern Medicine?
The new data highlighting the effectiveness of blue light cystoscopy compared to white light cystoscopy in detecting bladder cancer cells should not undermine the value of white light technology. The optimal approach during TURBT involves using both blue and white light cystoscopy to achieve the best results, as each provides crucial information that the other cannot. Blue light cystoscopy alone cannot be relied upon due to its potential for false positives in areas of inflammation, where increased vascularity triggers the heme biosynthesis pathway. The increased activity of this pathway allows for the accumulation of photoactive porphyrins, giving rise to the color observed during TURBT. This fluorescence can lead to unnecessary resections.
By alternating between blue and white light, physicians can ensure only pathological tissue is removed. Concerns about Cysview staining the entire bladder and hindering white light visualization can be mitigated with proper bladder washout, allowing for a thorough and accurate examination using both technologies.
[Dr. Suzanne Merrill]:
I think that gets at the point, too, when we talk about the logistics of using this technology, is that you do want to use both white light and blue light together. That you really should not only resect under blue light, for example. That you do want to use both information gained from when you're doing your cystoscopy under white light as well as the information gained under blue light. That's where you're going to get the best accuracy.
[Dr. Suzette Sutherland]::
Why do you say that? Is that more for our learning purposes so then we can go back and say, "This is what it looked like in white and now I see it on blue. Ergo, next time I'm going to know that white light little ditzel I didn't think was important is important," or is there more to it?
[Dr. Suzanne Merrill]:
I guess there's certainly a learning to it. I think, again, white light is what has been around historically and traditionally. It's important that blue light, again, how this technology works with Cysview and this optical imaging agent and that it accumulates most preferentially in cancer cells. It can also accumulate in areas of trauma and areas of inflammation, where you have, again, this increased vascularity and heme biosynthesis taking place and these photoactive porphyrins in high accumulation.
Ultimately, they've looked at, with these pivotal studies, what the false positive rate is between use of blue light and white light. There really is not a significant difference between the two. We do see, again, where the false positives are occurring are occurring at sites of, again, trauma, potentially previous resection sites, especially on the margins. You can see this happen at the areas of scar. Certainly, if there is active inflammation infection is where this can happen.
It is important to, again, use your judgment compiled together from both the white light and the blue light as to whether or not you decide to take a biopsy, do a full scraping resection.
[Dr. Suzette Sutherland]::
If we think real practically, when you put the Cysview in it, they sit there for an hour and it colors the bladder-- we'll get into the workflow in a minute-- it colors the bladder so when you take them to the OR there and put in the scope, it's already all colored. You've lost your absolute white light. You can still see. Everything looks still the same on white light or are there differences on white light with Cysview in?
[Dr. Suzanne Merrill]:
No, there shouldn't be. We can certainly talk about the logistics. It's important. One of the things when you do, you take that patient into the OR, they have the Cysview in their bladder still. You evacuate it. After either, they come in with the catheter clamped or if they're holding it naturally, evacuate it with the catheter, evacuate it with the scope. Then you should actually cycle the bladder with, again, your saline, wash it out, especially if it's sat in the bladder for longer than that recommended dwell time of an hour.
It's definitely accumulated more, so the blue light gets a little bit challenging initially unless you cycle the bladder a couple of times and look. That white light visualization should not be infringed upon because of that optical imaging agent in there.
[Dr. Suzette Sutherland]::
Okay. That was really the big question. I think sometimes I hear people wonder if it ruins your ability to get a good white light look. You're saying no, you still get a good white light look and then you turn on the blue light imaging and you get your blue light, right?
[Dr. Suzanne Merrill]:
Yes. You got it.
Additional resources:
[1] Daneshmand S, Bazargani ST, Bivalacqua TJ, Holzbeierlein JM, Willard B, Taylor JM, Liao JC, Pohar K, Tierney J, Konety B; Blue Light Cystoscopy with Cysview Registry Group. Blue light cystoscopy for the diagnosis of bladder cancer: Results from the US prospective multicenter registry. Urol Oncol. 2018 Aug;36(8):361.e1-361.e6. doi: 10.1016/j.urolonc.2018.04.013. Epub 2018 May 30. PMID: 29859728.
[2] Di Stasi SM, De Carlo F, Pagliarulo V, Masedu F, Verri C, Celestino F, Riedl C. Hexaminolevulinate hydrochloride in the detection of nonmuscle invasive cancer of the bladder. Ther Adv Urol. 2015 Dec;7(6):339-50. doi: 10.1177/1756287215603274. PMID: 26622319; PMCID: PMC4647142.
Podcast Contributors
Dr. Suzanne Merril
Dr. Suzanne Merrill is a urologic oncologist with Colorado Urology in Denver, Colorado.
Dr. Suzette Sutherland
Dr. Suzette Sutherland is the director of female urology with UW Medicine in Seattle, Washington.
Cite This Podcast
BackTable, LLC (Producer). (2024, August 27). Ep. 186 – Blue Light Cystoscopy: Improving Bladder Cancer Detection [Audio podcast]. Retrieved from https://www.backtable.com
Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.
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