Read the Full Video Transcript

Zachary Klaassen: Hi, my name is Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center. I'm delighted to be joined on UroToday with Ali Nasrallah, who is a urology resident at UTMB Galveston in Texas.

Ali, thanks very much for joining us today.

Ali Nasrallah: Thank you, Dr. Klaassen and the UroToday team for granting me this opportunity today to present our work. This is a project that we're quite proud of, and it's a combination of a fantastic collaboration between multiple institutions.

Zachary Klaassen: Fantastic. So you guys presented this at the AUA South Central Section meeting, is that correct?

Ali Nasrallah: Yes, that is correct.

Zachary Klaassen: Wonderful. I'd love for you to walk us through those slides, and then we'll have a discussion after your presentation.

Ali Nasrallah: I'd like to present our study entitled "Bladder Cancer Recurrence Analysis in Veterans and Outcomes," which is BRAVO for short. And as you can see, my co-authors have worked day and night on this data. Disclosures include that this study was conducted with the financial support of Photocure.

As a brief introduction, as you may know, bladder cancer is the sixth most common cancer in the United States, and there's a projected over 83,000 new cases in 2024 and over 17,000 projected mortalities in 2024. Most of the newly diagnosed bladder cancer is non-muscle invasive disease, and the management of which mainly focuses on reducing the recurrence of this cancer and also attempting to prevent it from progressing into muscle-invasive disease and eventual morbidity and mortality. One technology that has been used is blue light cystoscopy, and has been shown to improve cancer detection rates, as was demonstrated in prior studies and literature. However, the real-world impact of blue light cystoscopy on non-muscle invasive bladder cancer and oncologic outcomes of it, especially in equal access settings, have not been well demonstrated yet. So this is why we aim to compare the impact of blue light cystoscopy on these outcomes in non-muscle invasive bladder cancer.

The study population was comprised of patients from the VA Informatics and Computing Infrastructure system with pathologically confirmed NMIBC between the years of 1997 and 2021. The two cohorts were patients who underwent blue light cystoscopy at any point during their treatment or exclusively underwent white light cystoscopy. After patients met all the inclusion criteria, we performed propensity score matching, and we ended up with a total of 626 patients in the final analysis.

As you can see in our table here, this table compares our two cohorts, the blue light and the white light group. They had similar demographics and disease risk classification after matching. Ninety-eight percent were males, 10% of patients were Black, and only 8% were diagnosed outside of the VA system. The majority were smokers at 82%, and we need to highlight that 61% of our patients had high-risk disease. Looking at the post-diagnosis treatment row, we noticed that the blue light cystoscopy group received more BCG and also more intravesical chemotherapy than the white light cystoscopy group, but there was no difference in the definitive treatment categories, which included systemic chemotherapy, radical cystectomy, or radiation treatment.

Moving on to the Kaplan-Meier analysis and also the Cox proportional hazard ratios, from our 626 patients, we had 159 cases with recurrence of bladder cancer, which is 25%. Sixty-four of these patients recurred in the blue light group and 95 in the white light group, which is 20% and 30%, respectively. Looking at the Kaplan-Meier curve, we show that the risk of recurrence was significantly lower for blue light cystoscopy with a recurrence-free survival at three years of 75% for blue light versus 67% for white light. The multivariable analysis that we performed showed a significantly lower risk of bladder cancer recurrence with the use of blue light cystoscopy compared to white light only, with a hazard ratio of 0.62.

We also noted that high-risk disease was associated with over double the risk of recurrence in our population. And then looking at cancer progression, there were 38 cases, which was 6%, of cancer progression in our cohort. Seventeen of these cases, so 5%, occurred in the blue light group and 21, which is 7%, occurred in the white light group. Patients who underwent blue light cystoscopy had a reduced risk of progression with a hazard ratio of 0.71. However, this did not achieve statistical significance. We also looked at high-risk disease classification, and that was associated with over fourfold increased risk of cancer progression. We also had a small sub-analysis conducted to assess the impact of blue light versus white light cystoscopy on reducing the risk of undergrading non-muscle invasive bladder cancer when used, and we noted that blue light cystoscopy was able to detect higher-grade non-muscle invasive cancer in 33 versus nine patients for white light with a hazard ratio of 1.92.

So in summary, we found that recurrence risk at three years was significantly reduced with the hazard ratio of 0.62. Progression risk at three years was reduced; however, this was not statistically significant. And looking at the treatment differences, the blue light cystoscopy patients received more BCG and also received more intravesical chemotherapy versus the white light cystoscopy-only patients, and there were no differences as far as definitive treatment rates were concerned.

What are the take-home messages from this? Firstly, in this high-risk NMIBC predominant cohort, we were able to show that blue light cystoscopy use was associated with the reduced risk of cancer recurrence. It was also associated with an increased use of intravesical therapies, but not definitive treatment need, which poses the question, does blue light cystoscopy help direct therapy in a more appropriate direction for patients? And these findings provide real-world evidence for the oncologic benefits of utilizing blue light cystoscopy.

Thank you very much.

Zachary Klaassen: Ali, fantastic presentation, and I want to congratulate you on just some beautiful work, especially using a real-world cohort such as the VA.

I'd like you to expand a little bit on one of your take-home messages where you talked about blue light cystoscopy leading to perhaps more intravesical therapy use and less definitive therapy. Do you think that... What's your thoughts on how blue light is maybe directing patients more appropriately toward intravesical, maybe a little less on the definitive therapy side of things?

Ali Nasrallah: Yeah, it's a quite interesting point to see in the data, and I think we need to acknowledge that the premise of blue light cystoscopy is to improve bladder cancer detection and that the oncologic outcomes largely rely on how that information is acted upon with regards to treatment plans. The blue light cystoscopy is a tool that needs to work in tandem with optimized treatment plans to eventually result in improved oncologic outcomes. And our study here, which took place in an equal access setting, we found that the blue light cohort did receive more intravesical BCG and more intravesical chemotherapy even after matching based on disease risk class, which is important to note. So possibly, the use of blue light helped uncover additional lesions, possibly reduced risk of undergrading, thus resulting in more appropriate treatments for these patients.

Zachary Klaassen: Yeah, absolutely. That's a great answer.

When we look at these real-world studies and assessing interventions in populations that are outside of a clinical trial, and we know that clinical trials are selecting healthier patients and patients that are going to probably do well, but these are important studies because they're really reflective of the patients we're treating in our clinics every day. And I really like, especially in the VA with a higher African-American population, you guys had 10% African-Americans, which is much higher than most clinical trials do when they're accruing patients. So having said all that, how does this demographic profile lead to more generalizability of your guys' results?

Ali Nasrallah: I think that's very important to look at, especially in bladder cancer. Although RCTs are crucial to determine the safety, efficacy, and effectiveness of treatments and interventions, we need real-world data to validate and to genuinely look at these conclusions that were drawn based on clinical trial populations and controlled settings. We've seen prior research that has shown that race is a well-studied risk factor influencing oncologic outcomes in bladder cancer specifically, and Black race in particular was associated with more advanced disease stage at diagnosis and possibly poor oncologic outcomes, possibly due to biologic or social reasons.

Now, clinical trials in the bladder cancer world, and even looking more specifically at blue light cystoscopy trials, may lack some generalizability due to this point. Looking at some of the trials that we looked at as part of a literature review, one pivotal study that was published about 12 years ago had only 1.1% or 1.5% Black patients in that trial. Another trial that was published in 2022, so just two years ago, excluded race entirely from their reported demographic variables in their population.

In our study, which takes place in a real-world equal access setting, it appears to capture a more representative sample of patients, which suggests that the impact of blue light cystoscopy on reducing the risk of recurrence of bladder cancer might be independent of race.

Zachary Klaassen: No, that's a very good point. The last point I want to bring up, and this is consistent across several studies, we certainly see blue light decreases the risk of recurrence, but maybe not as much on the progression side. Perhaps this is a sample size and event issue. You guys had 6% of the patients have progression in your study. What are your thoughts on the fact that we're seeing consistent recurrence decrease but maybe not as much progression?

Ali Nasrallah: Yes, and I think that is a theme that's been noted in several studies, whether clinical trials or cohort analyses. One possible explanation, as you alluded to, is the paucity of progression events within this three-year follow-up period that we had. So we only had 38, so 6%, progression cases which we found in our cohort. As a result, could a larger sample size or even a longer follow-up period increase that number so that statistical significance may be reached? That is possible.

I think another interesting angle to look at is something that was published back in 2016, another study which changed the definition of progression and that found that prolonged the time to progression. So could we be defining progression in a way that may be hindering those results from being shown? Fundamentally, I think, if blue light cystoscopy is contributing to improved detection of cancer, reducing the risk of undergrading the tumors, reducing the risk of recurrence of bladder cancer, ultimately, it should have, in theory, an impact on reducing progression, and we hope to elucidate this impact in future investigations.

Zachary Klaassen: Absolutely. You nicely already recapped your take-home messages in your last slide, but I'd love for you to maybe just run through those again for our UroToday listeners.

Ali Nasrallah: Yeah. A couple of take-home messages I think which we can take with us at the clinic tomorrow is that blue light cystoscopy is a useful modality that can help us reduce the risk of bladder cancer recurrence, especially for our patients with high-risk disease. And blue light cystoscopy is also a diagnostic tool that could potentially help us redirect the treatment plan for our patients into more appropriate pathways if the information that we get from it is acted upon appropriately.

Zachary Klaassen: Wonderful. There was some great data presented at the South Central meeting, including your BRAVO study. Ali, great job on the interview. Congratulations on this important work and thanks for joining us on UroToday.

Ali Nasrallah: Thank you very much, Dr. Klaassen. It was a pleasure today.