Yair Lotan: Hello. My name is Yair Lotan. I'm a professor of Urology at UT Southwestern Medical Center. So today I'm going to talk a little bit about the consensus statement on flexible blue light cystoscopy with Cysview. There is an article that was published in Nature Reviews and was a consensus statement from multiple experts in bladder cancer discussing the role of blue light flexible cystoscopy with hexaminolevulinate in non-muscle invasive bladder cancer.

The document was based on an expert consensus group that met at the AUA in 2018 with a goal of reviewing the body of data for blue light cystoscopy with Cysview and to consider its utility in various clinical areas. The group consisted of 17 specialists in bladder cancer who are experienced with use of blue light cystoscopy with Cysview. Fourteen of the specialists were investigators in the 308 trial, which was a pivotal trial evaluating flexible blue light cystoscopy with Cysview for surveillance of patients with intermediate and high-risk bladder cancer. This trial led to FDA approval of Cysview and flexible blue light cystoscopy for use of surveillance of bladder cancer in the clinic.

The group reviewed the highest level of evidence involving blue light cystoscopy with Cysview for TURBT, the evidence for flexible blue light cystoscopy with Cysview for surveillance, and also evaluated future directions.

The main goal of surveillance of bladder cancer is to determine whether or not a patient has recurrence or progression. Based on that, all patients could benefit from enhanced cystoscopy either to reassure the patient and provider that no cancers were missed or to help identify suspicious areas that need biopsy or at a minimum closer attention. However, early in the adoption of flexible blue light cystoscopy with Cysview, it's important to select which patients are going to be most suitable for the procedure and who will most likely benefit, for the fact is that there are some additional logistical concerns that may add a little bit of the work effort to perform blue light cystoscopy. As such, it's important to really identify those patients who are most likely to benefit to justify the added expense and at a time to perform the procedure.

It's well known that the highest likelihood of recurrence is at the initial three-month surveillance visit. The reason for this is that patients could have either a new tumor develop after a TURBT or they may have had residual cancer that was missed at the initial TURBT that had a chance to grow. Based on this, the consensus panel really felt that the three-month time point was probably the best use for flexible blue light cystoscopy, and 100% of the panel agreed that for high-risk patients there was going to be an added benefit to using flexible blue light cystoscopy at that time point.

For intermediate-risk patients, the majority of the panel agreed that there would be a role for blue light flexible cystoscopy at three months. The majority of the panel did not think that there was going to be a high utilization or utility for low-risk patients at three months, and this is in large part because patients with small isolated low-grade tumors are unlikely to progress, even if missed with white light cystoscopy.

The second question that was addressed was how frequently should flexible blue light cystoscopy be utilized in the first two years? The majority of the panel thought that for high risk patients there would be a value at three months, six months, and then probably every six months for the first two years, largely because these are patients who are going to get BCG induction and maintenance, and it was important to identify which patients are becoming BCG unresponsive. About a third of the panel thought that frequency of use dependent on the findings at three months cystoscopy evaluation, and this was reasonable because if a patient had a recurrence at that time point, it might impact their risk for future recurrences down the road or potentially progression.

The panel also felt that it was an important endpoint to use flexible blue light cystoscopy with Cysview during surveillance and determining BCG responsiveness especially in patients with carcinoma in situ. It's been shown that carcinoma in situ is much easier to identify with blue light cystoscopy and that rates as high as 25% to 30% increased detection have been found with blue light over white light alone for carcinoma in situ.

There were several specific clinical scenarios that were evaluated by the panel. About 76% thought that blue light flexible cystoscopy might be useful before initiating intravesical therapy in patients where residual disease is a concern, especially if a TURBT was performed elsewhere or without blue light flexible cystoscopy, or blue light cystoscopy at the time of surgery.

Similar rates agreed that blue light cystoscopy would be useful at the time of office biopsy and fulguration, especially in patients with multiple recurrent low-grade tumors to help identify all disease at the time of the office procedure. 88% agreed that patients with positive cytology and normal white light cystoscopy might benefit from flexible blue light cystoscopy. Again, this was to help identify carcinoma in situ, which is a concern in patients with a positive cytology and normal white light cystoscopy.

Finally, in patients with equivocal lesions who have erythema during white light cystoscopy with negative cytology might benefit from an office blue light cystoscopy prior to being taken to the operating room with a hope of avoiding anesthesia if the equivocal lesion did not appear suspicious.

To summarize, there was a strong recommendation for flexible blue light cystoscopy at the initial three-month cystoscopy in patients with high or intermediate risk according to the AUA guidelines. The frequency of use really was at three and six months for high-risk patients and then every six months for the first two years. Specifically for patients with concern for residual disease, it might be valuable to do it prior to initiating intravesical therapy, and most panelists recommended use at the time of office fulguration to make sure no additional lesions are missed at the time of that procedure, especially for low-grade tumors, and may have a role in evaluating patients with positive cytology or equivocal lesions.

So if you look specifically at low-risk patients, the main use is probably for biopsy and fulguration and if the patient has a positive cytology. This would be rare for low-risk patients because they all have low-grade disease and so very few of them would progress to high-risk disease.

The value at the time of initial surveillance and if a patient was going back to the operating room for a repeat TURBT, probably less of a consensus regarding the role for surveillance at three or six-month intervals for two years. The majority did not feel that that was necessary, but they did feel that there was a role prior to intravesical therapy if there was concern for residual disease and again for patients with equivocal lesions or positive cytology.

The strongest recommendation was for high-risk patients, both at the time of a repeat TURBT and initial surveillance, and the majority of the panel felt that it was useful during surveillance in the first few years and again in specific scenarios such as concern for residual disease, positive cytology, or equivocal lesions.

Future directions focus on efficacy and low and intermediate-risk disease and the effects on long-term outcomes. The hope is that if you can detect disease earlier and identify patients with BCG unresponsive disease, that additional treatments can be provided to a patient, possibly use of clinical trials or early cystectomy and that this would improve long-term outcomes. There's also a need to determine the cost-effectiveness and the utility of the technology when balanced against the time added for the patient to come in for instillation and for the staff to instill the Cysview. And there would be value for clinical trials to test utility of Cysview as photodynamic therapy, and possibly use of treatment as a novel precision-based approach that might be less invasive. However, a lot more research will be needed before this could be used as a therapy, and primarily right now the accepted use is for detection of a disease that is missed with white light. Thank you for your time.