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BackTable / Urology / Article
Blue Light Cystoscopy in Bladder Cancer: A Research-Based Perspective
Javier Prieto III • Updated Oct 7, 2024 • 143 hits
Bladder cancer is one of the most common cancers, with the number of cases continuing to rise over time. The traditional approach to detecting bladder cancer and planning treatment starts with a transurethral resection of the bladder tumor (TURBT) to remove all tumors for pathological evaluation. For decades, the standard technique has been to use white light cystoscopy to identify cancer pathology inside the bladder. However, years of research have highlighted the limitations of this method and shown how patient outcomes can improve when blue light cystoscopy is incorporated into bladder cancer workups.
Urologists Dr. Suzanne Merrill and Dr. Suzette Sutherland provide a comprehensive overview of the current data on using blue light cystoscopy during TURBT procedures and the advantages it offers to both physicians and patients. They also discuss the existing patient outcomes when only white light cystoscopy is used and how the field of urology can advance by making blue light cystoscopy part of the gold standard for bladder cancer treatment.
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 is becoming increasingly prevalent, with men being affected in the majority of cases worldwide.
• Treatment outcomes remain suboptimal, as the standard practice for bladder cancer work-up has not fully incorporated blue light cystoscopy during TURBT procedures. Clear evidence supports the benefits of using both white and blue light technology, which can help reduce the severity of risk stratification for bladder cancer.
• There is overwhelming data demonstrating the effectiveness of blue light cystoscopy for diagnosing and treating non-muscle invasive bladder cancer (NMIBC); however, awareness of its potential impact across all bladder cancer variants remains low within the urology community.
• Research shows that incorporating blue light technology in all possible bladder cancer cases improves sensitivity and specificity, leading to better health outcomes for patients.
• The absence of blue light cystoscopy in bladder cancer cases has proven to be detrimental, as past studies have shown. Relying solely on white light cystoscopy has resulted in double-digit percentages of incorrect staging and grading for affected patients. One significant error has been the missed diagnoses of carcinoma in situ (CIS) variants, a concern that has gained attention when blue light cystoscopy is not incorporated into treatment.
Table of Contents
(1) Epidemiology & Risk Stratification of Bladder Cancer
(2) Findings Encourage the Use of Blue Light Cystoscopy for All Bladder Cancer Variants
(3) Bladder Cancer Outcomes in the Absence of Blue Light Cystoscopy
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Epidemiology & Risk Stratification of Bladder Cancer
Bladder cancer is currently the fourth most common cancer in men and the sixth most common cancer in the United States. Men are affected more frequently than women, though the reasons for this disparity are still being explored. Approximately 60% of bladder cancer cases are classified as superficial, which raises concerns about recurrence, as more than half of these cases are expected to recur within one year, with the risk increasing over time. Given the rising incidence of bladder cancer, it is crucial to identify the best practices for treating patients moving forward.
The AUA classifies bladder cancer risk into low, intermediate, and high categories for diagnosed patients. This risk stratification is primarily based on the cancer stage, which is determined through TURBT. A TURBT reveals the depth of invasion, focality, and grade of the tumor(s), collectively providing the cancer stage. The goal of TURBT is to remove all tumors in the bladder, extending down to the muscle layer for optimal pathological evaluation. [1] However, bladder cancer outcomes have been suboptimal due to the lack of mandatory blue light cystoscopy use in identifying non-muscle invasive bladder cancer. Despite more than 20 years of evidence showing that blue light cystoscopy can detect up to 45% of tumors missed by white light cystoscopy, the urology field has been slow to fully adopt this technology as a standard part of treatment. [2]
[Dr. Suzette Sutherland]:
First of all, just a couple of good fun facts, I suppose, not so fun, we know bladder cancer, it seems like it's getting even more common today than it was even when I was training. It's quite common more so in men than women. Tell us the statistics around the epidemiology today.
[Dr. Suzanne Merril]:
Yes, of course. It's a lot more surprising when we're talking to our patients about how common bladder cancer is. In 2024, it ranks as the fourth most common cancer in men and the sixth most common cancer in the US for both men and women. Superficial bladder cancer actually comprises of greater than 60% of all our new diagnoses that go on. When people get superficial bladder cancer, the main concern is that there is a high risk of recurrence. That recurrence in just year 1 can be as high as 60% and obviously escalates going forward in time.
This discussion we're going to have today about diagnosing it, getting the right stage and grade, and fully taking care of it when we go in for that TURBT is absolutely critical, for both our patients and getting them on the right track for treatment.
[Dr. Suzette Sutherland]:
Right. We know when we talk to patients about cancer, oftentimes I say the C word before I say the word, right? Because it's so frightening, right? We as physicians and surgeons know that one person's cancer isn't another person's cancer, especially when we're talking about different organs, but even the case when you're talking about bladder cancer, and we know the earlier you find it, it's totally treatable, right? When it's late in the diagnosis, it's a whole nother issue for the patients, right? That's another thing that we're talking about here today, how we can do a better job at detection early and utilizing some of the newer tools that we have.
Let's look at the AUA guidelines really quickly for the risk stratification. We know it's determined by low risk, intermediate, high risk, and the things that come into play for that, much of it histological things, and that's where our technology can help us. Can you briefly go into a little bit of the main points that go into our risk stratification today?
[Dr. Suzanne Merril]:
Yes, of course. Really importantly with the risk stratification that our AUA outlines, which is low, intermediate, and high risk, and nowadays we're even talking about a very high-risk group that some of us use to specify patients that are in need of a more comprehensive talk about even entertaining invasive surgery such as cystectomy. What goes into the risk stratification with patients is specifically the stage, so what we gain from that TURBT in terms of the depth of invasion, and then grade, as well as focality, so multiple tumors, and then the size of the tumor plays a role.
For example, if we find CIS in a patient, that automatically, that stage, if you will, escalates the patient to certainly the high-risk group. Then if we have a couple of features such as CIS, maybe also T1, if they have lymphovascular invasion, then a lot of us are thinking such patients should fit into even a higher escalation risk category such as a very high-risk group. Those are the patients that we're really concerned about, not only in terms of recurrence but very much progression of disease.
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Findings Encourage the Use of Blue Light Cystoscopy for All Bladder Cancer Variants
Based on years of compelling data, the 2024 AUA/SUO guidelines now recommend that medical professionals use blue light cystoscopy for patients diagnosed with non-muscle invasive bladder cancer (NMIBC). For bladder cancer patients without NMIBC, the guidelines advise urologists to include blue light imaging during TURBT to improve detection and reduce recurrence. The AUA/SUO made this recommendation because blue light cystoscopy benefits all affected patients, supported by a 2013 meta-analysis that demonstrated 25% greater detection of Ta and T1 lesions compared to white-light cystoscopy alone. The data also indicate that incorporating blue light technology reduces the recurrence rate by 11% and can delay the onset of recurrence.
The use of blue light cystoscopy can also extend to detecting uncommon variants of bladder cancer, as it is not limited to typical forms. While more evidence is needed to fully assess its effectiveness in detecting variant pathologies, the current outlook is promising. From a histological standpoint, the accuracy of detecting the correct grade of bladder cancer cases is 76% when only white light cystoscopy is used. This accuracy increases to 91% when blue light cystoscopy is used instead of white light alone. The highest accuracy, 98.5%, is achieved when both white and blue light cystoscopy are used together. As the evidence continues to build, the field of urology is increasingly moving toward using both white and blue light cystoscopy in the treatment of bladder cancer.
[Dr. Suzette Sutherland]:
Again, we know this totally changes the prognosis of the patient, right, and what we're going to do next or what we should be advocating for next. I just wanted to make that point that when we look at the newer-- I think they came out in 2024, yes, just last spring-- the AUA/SUO guidelines concerning this, they actually say in patients with non-muscle-invasive bladder cancer, we should be offering blue light cystoscopy.
Now, they make the caveat. At the time of TURBT, the caveat is, if available, to enhance detection and decrease recurrence. It's a moderate grade/grade B evidence strength, but again, they do put that word should in there, as opposed to saying could, right? The data is pushing a little more towards or pointing towards the real potential, the benefits of this blue light imaging.
[Dr. Suzanne Merril]:
Yes, that's very true. I think the data, over time, has shown us that blue light is a technology that should be offered to our patients, that it has good enough evidence behind it, that it can impact our patients' course of disease and outcome. Even back in 2013, there was a meta-analysis of 9 studies which ultimately showed that detection of Ta and T1 lesions may be up to 25% greater with blue light cystoscopy and use of Cysview than compared to white light.
Overall, this translated, looking at the raw data from this meta-analysis, that the rate of recurrence with use of blue light can be reduced by about 11% and it can certainly prolong the time to recurrence by about 7-ish months. Some pretty impactful evidence behind this technology.
[Dr. Suzette Sutherland]:
Then, I guess to take it to another direction a little bit, these patients that have mixed, low and high-grade histology or uncommon variants, is it picked up by the uncommon variants as well so it can help to determine these more high-risk patients?
[Dr. Suzanne Merril]:
That's a really good point to bring up. I think, at least right now, evidence hasn't really panned out, in regards to does it get picked up by more variant histologies such as small cells, such as micropapillary, sarcomatoid, which we all know can be seen. It's more rare, but can be seen, certainly in the superficial setting. These randomized studies, multi-center perspective in nature that really set this optical imaging agent up for FDA approval and use today didn't really sort out the variant histology, if you will.
What we know is that certainly it does get picked up more by more aggressive type lesions like CIS, but can certainly still be used in the low-grade setting. As you mentioned, in our superficial bladder cancer, the mixed-grade heterogeneity is up to 30%, and so it's just very important to be able to ensure that we're capturing, if you will, the truth about what is in a patient's bladder because, for example, with our intermediate risk category of the AUA, that contains patients that are low-grade, as well as high-grade patients.
High-grade patients have to have less than a 3-centimeter tumor size to it, but the recommendations for patients that fall in that intermediate risk category is that the provider should consider intravesical therapy. Excuse me. It says just should consider. It doesn't actually recommend as strongly as if you're in the high-risk category to give intravesical therapy, so it leaves it up to the provider as to whether that patient should go on further with intravesical treatment or not.
The problem with that, if we've misclassified a patient and they actually, for example, have a CIS lesion that we missed, or it was a predominantly low-grade papillary lesion that was visualized but yet you missed that one smaller high-grade lesion sitting in the back of the bladder, smaller, then that patient might not be placed into the right risk category and therefore not receive the appropriate intravesical treatment going forward.
[Dr. Suzette Sutherland]:
Can you refresh my memory? If it's mixed, is there a certain percentage of high-grade to put them into the high-grade category, like 5%, or is it any high-grade?
[Dr. Suzanne Merril]:
No. Very good point. You're right. It is actually 5% is only what is needed within the total specimen volume to deem that patient now as high-grade.
[Dr. Suzette Sutherland]:
That's obviously a very important junction in whether a patient is deemed intermediate versus high, getting intravesical chemotherapy or intravesical BCG, and the risks associated with the intravesical therapy, right? That clinical decision, taking out all of the objective things and looking at the patient, having the patient help make that decision, what they're willing to do, it's not easy, right?
The more we have on the diagnostic end of things to point our fingers towards a high-risk situation to tell us to do the intravesical therapy, it obviously makes our job somewhat easier to some degree, right? Because that decision-making process is out of it, the judgment part. Also, I think for the patient to accept doing intravesical therapy, it's not an easy thing. You do this all the time, right? This isn't my specialty, but I do have some bladder cancer patients that are women in my practice and it's never an easy thing for those women to undergo that and some of the hardships associated with the symptoms thereafter and so on and so forth that they go through, right? This really would help make that diagnosis.
I found some information on the sensitivity, the accuracy, right? Looking at what's seen through the eye and then what's seen histologically. With white light, the accuracy is 76% compared to blue light, 91%. Then combination, white plus blue, 98.5%. Now, clearly, that comes from, I'm sure, one conglomerate study of looking at things, but still, the difference there is really poignant.
Bladder Cancer Outcomes in the Absence of Blue Light Cystoscopy
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The enhanced visualization and resection provided by blue light cystoscopy have contributed to the identification of more bladder cancer cases, including high-grade instances. A 2018 study conducted via a prospective multicenter registry in the United States supports this observation. The use of blue light technology resulted in a 14% increase in tumor upstaging, and 8% of patients were found to have bladder cancer that was missed when only white light cystoscopy was used. Additionally, the study revealed that 6% of patients were assigned a higher risk status, as white light cystoscopy had underestimated the severity of their bladder cancer pathology.
While blue light cystoscopy is particularly beneficial in detecting non-muscle invasive bladder cancer (NMIBC), it also proves highly effective in identifying carcinoma in situ (CIS), which can be challenging to detect. White light cystoscopy has been shown to be less effective for CIS detection. Traditional methods using TURBT with white light cystoscopy have missed CIS up to 45% of cases, which were only confirmed after cystectomy. A cystectomy, a procedure to remove part or all of the bladder, can be performed either openly or robotically. Cystectomies are categorized as either radical or simple: a radical cystectomy removes the bladder, surrounding organs, and lymph nodes, while a simple cystectomy does not. [3] Missing a diagnosis like CIS can easily shift a patient's risk stratification from intermediate to high risk, significantly increasing the likelihood of malignancy. This concerning data supports the notion of establishing the combination of white and blue light cystoscopy during TURBT as the gold standard for bladder cancer work-up.
[Dr. Suzette Sutherland]:
Let's talk a little bit about, too, upward migration of staging oband the numbers around that and how blue light has opened our eyes. We've had a little bit of this discussion, too, but not as much about just patients that have low risk, and then suddenly, because of blue light, you're able to get a better visualization, better resection, so on and so forth. You found that there are studies out there showing that, oops, they really seen a trend of upward migration, right, of more high-grade patients out there. Isn't that true? With the use of blue light, as we've looked over the last handful of years or so.
[Dr. Suzanne Merril]:
In 2018, Daneshmand published in Neurologic Oncology some real-world data, which is really helpful to understand, again, outside of the very strict criteria of a randomized trial, how are people using this data and what are the results. Through a US prospective multicenter registry, they found that use of blue light can result in a rate of upstaging of about 14%. How that breaks down is that ultimately, 8% of patients were identified with cancerous lesions, whereas with the white light, they were not, so that stages them to having cancer, and that 6% of patients actually had an increase in that risk status.
What we were talking about before, that vulnerable intermediate risk category, where, again, if they were found to have either a high-grade lesion whereas initial white light resection would have only shown maybe a white low-grade lesion, or they would have found maybe a CIS lesion, then they're popping up into that high-risk category. Therefore, again, would be set on a path of recommended intervesicular therapy after their resection. Really important stuff, for sure.
[Dr. Suzette Sutherland]:
Yes. A lot of this, of course, is very helpful for patients that have non-muscle invasive, right, superficial cancer. Is there some data to show, with the use of blue light, it's really helped us to identify the muscle-invasive patients as well, upstaging to that level, or is that-- Usually those are patients that have a little bit more burdening, also, their tumors can look a little aggressive, even on white light, and so sometimes we have more of a hunch of that than we do when people just have very small CIS areas or things like that. I just wonder if the data also shows it's been helping us to identify patients to move them from the non-muscle invasive into the muscle invasive category.
[Dr. Suzanne Merril]:
That's a good question, for sure. I think the data is more about showing, again, risk migration in the non-muscle invasive categories rather than switching to a T1 to T2 stage, for example. Certainly, this technology really has shown us that it is this CIS, which, as we mentioned before, is a very elusive disease under normal, traditional white light capacity, and that ultimately, historically, we've done a very poor job in detecting CIS.
In 2023, there was a report looking at a cystectomy database and looking at what the path was retrieved from the whole-mount specimen, the cystectomy, compared to what was their initial diagnosis from the TURBT preceding the cystectomy. Ultimately, 45% of cases actually missed CIS. There is CIS in the cystectomy pathology, none detected in the TURBT.
That just gives you a hint that, "Gosh, if we're missing up to 45% of CIS in patients and that those patients would ultimately be transitioned up stage in risk status, if you will, to the high-risk category, maybe even the very high-risk category, we'd be having different conversations with our patients, ultimately setting them on a completely different, probably, cancer journey."
Additional resources:
[1] Guerero DN, Bruce A, Vayalapra S, Menon V, El Hadi M, Khashaba S. Improving the Quality of Transurethral Resection of Bladder Tumour (TURBT) Operative Notes Following the European Association of Urology Guidelines: A Completed Audit Loop Study. Cureus. 2022 Oct 10;14(10):e30131. doi: 10.7759/cureus.30131. PMID: 36246089; PMCID: PMC9550198.
[2] Oude Elferink P, Witjes JA. Blue-light cystoscopy in the evaluation of non-muscle-invasive bladder cancer. Ther Adv Urol. 2014 Feb;6(1):25-33. doi: 10.1177/1756287213510590. PMID: 24489606; PMCID: PMC3891293.
[3] Aminoltejari K, Black PC. Radical cystectomy: a review of techniques, developments and controversies. Transl Androl Urol. 2020 Dec;9(6):3073-3081. doi: 10.21037/tau.2020.03.23. PMID: 33457280; PMCID: PMC7807330.
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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