Contemporary Advances in the Endoscopic Evaluation and Diagnosis of Bladder Cancer

Madrid, Spain ( Dr. Daneshmand gave an overview of the novel endoscopic techniques used in bladder cancer. These include the Narrow Band Imaging (NBI), Optical coherence tomography (OCT), confocal endomicroscopy, and blue light cystoscopy (BLC), also known as fluorescent cystoscopy, which is also the most extensively examined modality.  

NBI works by filtering white light into specific light wavelengths that are absorbed by hemoglobin, providing enhanced visualization of capillary networks and mucosal morphology. In this technique papillary tumors appear dark green or brownish green, owing to enhanced visualization of the submucosal fibrovascular stalk, as can be seen in figure 1. It demonstrates the great contrast between the two morphologic types of bladder cancer lesions (papillary and carcinoma in situ [CIS]), as seen in figure 2. 

Figure 1 – Papillary bladder lesion seen in white light cystoscopy on the right and on narrow band imaging on the left:
Screenshot 2018 09 20 22.07.10

Figure 2- Papillary bladder lesion and CIS seen in white light cystoscopy on the left and narrow band imaging on the right: 

Screenshot 2018 09 20 22.07.47

The CROES study was a multicenter randomized trial of NBI assisted transurethral resection of bladder tumor (TURBT) vs. standard white light imaging assisted TURBT in primary non-muscle invasive bladder cancer (NMIBC) patients.1 A total 0f 965 patients were included, demonstrating a similar 12 months recurrence rate of 27.1% and 25.4% in white light cystoscopy and NBI, p=0.58. However, in low-risk patients, the risk for disease recurrence was 27.3% in the white light cystoscopy, compared to 5.6% in the NBI, p =0.002. There have been several studies, mostly small, examining the specificity and sensitivity of NBI. The sensitivity and specificity in these studies ranged from 93%-100%, and 69%-85%, respectively. NBI alone enabled identification of 12%-27% additional tumors. 

Next, Dr. Daneshmand discussed the blue light cystoscopy technique. This technique has been extensively studied to investigate the improvement in the detection of bladder tumors vs. white light cystoscopy. This modality is used with an optical imaging agent (Cysview® or Hexvis). In the US, Cysview® is used with the Karl STORZ D- light C photodynamic diagnosis (PDD). There have been five multicenter phase-three trials in the US, Canada, and Europe assessing its impact. Over 1800 patients with known/suspected bladder cancer are enrolled in these trials. In a meta-analysis of 9 studies, including over 2000 patients investigating the effect of blue light cystoscopy, it was shown that at least one additional Ta/T1 tumor was found in 24.5% of patients, p<0.001. Furthermore, 26.7% of the CIS patients were diagnosed with blue light cystoscopy only, p<0.001.2 This meta-analysis also demonstrated that the rate of recurrence was reduced by 10.9%, p<0.006 2 and the time to recurrence was prolonged from 9.4 months to 16.4 months, p=0.04 3 In another meta-analysis the rate of progression was reduced from 10.7% to 6.8%.4 This meta-analysis concluded with the recommendation to use blue light cystoscopy at first resection to allow more patients at risk of progression to be treated adequately and promptly.  

According to the National Comprehensive Cancer Network (NCCN) guidelines blue light cystoscopy may be helpful in identifying lesions not visible using white light cystoscopy. According to the American Urologic Association (AUA) guidelines, blue light cystoscopy should be offered to patients with NMIBC at the time of TURBT, if available, to increase the detection and decrease recurrence. NBI may be considered in patients with NMIBC to increase detection and decrease recurrence. 

A phase three prospective controlled comparative multi-center study in NMIBC patients included 17 centers in the US and compared surveillance with blue light flexible cystoscopy to TURBT when suspicion of recurrence arises with rigid blue light cystoscopy. A total of 21.5% and 34.6% of patients had tumors and CIS, respectively, detected only using flexible blue light cystoscopy. The rate of false positive lesions seen only with blue light cystoscopy was 8.6%, while a similar rate was demonstrated for white light cystoscopy only.5 

Another prospective multicenter study assessed patient-reported outcomes of blue light flexible cystoscopy in the surveillance of bladder cancer patients.6 This study showed that 90% of the patients found it worthwhile to undergo blue light cystoscopy and they would do it again and would recommend it to others. 

Dr. Daneshmand concluded his talk, reiteration the recommendation of the guidelines to use blue light cystoscopy at initial TURBT in patients with NMIBC suspicion. It is also recommended to use it for the assessment of suspected tumor recurrence in patients not previously  assessed using blue light cystoscopy, for assessment of patients with positive urine cytology but negative white light cystoscopy, in high risk patients, more than six weeks after the last instillation of BCG induction, and in patients with early re-TURBT (4-6 weeks after first resection). Lastly, the future role of blue light cystoscopy lies in the outpatient setting. 

Presented by: Sia Daneshmand, Keck Medicine USC, US 

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the Global Conference on Bladder Cancer 2018 - September 20-21, 2018 Madrid, Spain 

1. Naito S et al. Eur Urol 2016 
2. Burger et al. Eur Urol 2013 
3. Grossman et al. J Urol 2012 
4. Gakis et al. Bladder Cancer 2016 
5. Daneshmand S et al. J Urol, 2017
6. Smith AB et al. BJU Int, 2018
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