White light flexible cystoscopy remains the standard of care for evaluation of hematuria and bladder cancer, and transurethral resection of bladder tumor (TURBT) is the standard of care for staging and treatment. TURBT is the first-line treatment for bladder cancer, and an improvement in the quality of TURBT can lead to reduced risks of recurrence and subsequent cost savings. However, understaging of bladder cancer is common, as studies have shown that 50% of patients with high-grade Ta had persistent tumor at re-resection (15% upstaged to T1), and 48% of T1 tumors were upstaged to muscle-invasive bladder cancer.
Based on these statistics, it is imperative that we do better at performing TURBT. Cysview (5-HAL) was approved by the U.S. Federal Drug Administration in May 2010, but has been available in Europe as Hexvix since 2005. It acts as a precursor of photoactive photophyrins, and protoporphyrin IX selectively accumulates in rapidly dividing cells. Fluorescence with blue light (360-450 nm) leads to a bright red appearance of tumors. According to Dr. Schuckman, the benefits of Blue Light Cystoscopy (BLC®) with Cysview® are as follows:
- Increased detection of Ta/T1 tumors and CIS
- Increased ability to completely resect tumor
- Increased time to recurrence
- Potential for decreased progression
- Increased satisfaction and confidence with blue light flexible cystoscopy
Furthermore, the AUA/Society of Urologic Oncology (SUO) guidelines endorse enhanced cystoscopy, recommending blue light cystoscopy for positive cytology/negative white light cystoscopy (Grade B recommendation). Furthermore, the guidelines recommend that in non-muscle invasive bladder cancer, blue light cystoscopy should be offered if available at the time of TURBT (Grade B) in order to increased detection rate and decrease recurrence rate.
Dr. Schuckman then discussed tips and tricks of blue light technology including several pitfalls at the time of TURBT. The first pitfall is incomplete resection during TURBT, in which small papillary lesions may be missed. Her tip is that the edges of the resection should be well defined, which can be made easier by resecting/biopsying under blue light. A second pitfall is missed CIS during TURBT, which occurs in 20% of cases that use white light alone. Dr. Schuckman’s tip is to use blue light cystoscopy, move slowly, and check for false positives by identifying stable edges of the lesion. The third pitfall of TURBT is being unable to identify the ureteral orifice. This may be difficult during blue light cystoscopy as the urine jet during these cases is green. Her tip in these situations is to ask anesthesia to give a dose of Lasix, which helps with ureteral jet identification. Several tips and tricks for the logistics of TURBT with blue light cystoscopy include (i) using blue light for every case except obvious T2 lesions, (ii) using a dwell time of 30 minutes prior to the procedure, (iii) recording with a built-in recorder, and (iv) using the technology as a teaching tool for residents.
Flexible blue light cystoscopy with Cysview was U.S. Federal Drug Administration (FDA) approved in 2018 for bladder tumor surveillance based on data from a phase III multi-center study of 304 high-risk patients on surveillance (most patients were post-Bacillus Calmette-Guérin (BCG)).1 In this trial, 20.6% of tumors were detected with only flexible blue light cystoscopy, and 34.6% of carcinoma in situ was detected with only flexible blue light cystoscopy. Several uses of flexible blue light cystoscopy include (i) evaluation of patients post-biopsy for completeness of the resection, (ii) evaluation of response to intravesical chemotherapy, and (iii) surveillance of intermediate and high-risk patients. Several benefits of this technology using flexible cystoscopy include (i) management of patients in the ambulatory setting, (ii) early detection of significant lesions, and (iii) increased provider confidence and patient confidence.
There are several pitfalls associated with flexible blue light cystoscopy, including:
- Patient selection – low-risk patients are likely not well-served by routine use of blue light cystoscopy, whereas intermediate-risk patients should have a flexible blue light cystoscopy at their 3-month surveillance cystoscopy. High risk patients should have flexible blue light cystoscopy at their first and second (3 and 6 months) surveillance cystoscopy and then every six months for 2 years
- Patient flow through the clinic – it is imperative to teach staff and optimize dwell time/patient timing for cystoscopy
- “Green Urine” during cystoscopy – it is important to empty the bladder well or have the patient void prior to starting the procedure, and it is important to have the suction readily available in the clinic setting. Additionally, another tip is to irrigate out Cysview dye and urine prior to commencing the evaluation
- Inflammation vs disease? It may be difficult to differentiate these two entities, particularly in the post-BCG patients. In the phase III trial , the false positive rate was comparable between white-light cystoscopy and flexible blue light cystoscopy. Dr. Schuckman’s tip for this situation is the identify stable edges of potential disease and do “on the spot biopsies” in the clinic and avoid a trip to the operating room.
- Tangential view versus true positivity – this occurs in patients that have difficult (ie. trabeculated) bladders, where false-positive lesions disappear on closer inspection. Dr. Schuckman’s advice in this situation is to move slowly and move close to the bladder urothelium.
Dr. Schuckman concluded this presentation discussing tips and tricks for performing blue light cystoscopy with the following concluding statements:
- Blue light cystoscopy increases detection of clinically significant cancers
- More complete resection and lower recurrence rates are facilitated by blue light cystoscopy
- The false positive rates of blue light cystoscopy are similar to white light cystoscopy
- Flexible blue light cystoscopy allows for early identification and management of disease in the ambulatory setting
- Results from the phase III trial suggest that 95% of patients said they would recommend blue light cystoscopy, enjoy observing the clinic procedure, and would do it again
- Patients and providers express the feeling that “a more complete evaluation was completed” when using blue light cystoscopy
Presented by: Anne Schuckman, MD, Assistant Professor, Director, LAC+USC Urologic Oncology, Keck School of Medicine University of Southern California, USC, Los Angeles, CA
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, twitter: @zklaassen_md at the 2020 American Urological Association (AUA) Annual Meeting, Virtual Experience #AUA20, June 27- 28, 2020
1. Daneshmand S, Patel S, Lotan Y, et al. Efficacy and Safety of Blue Light Flexible Cystoscopy with Hexaminolevulinate in the Surveillance of Bladder Cancer: A Phase III, Comparative, Multicenter Study. J Urol 2018 May;199(5):1158-1165
Blue Light Cystoscopy with Cysview®: Tips and Tricks - Anne Schuckman