Detecting Invisible Bladder Cancers with Blue Light Cystoscopy - Beyond the Abstract

Blue-light cystoscopy (BLC) is a photodynamic diagnostic technique that augments the detection of occult disease missed under traditional white light. Instillation of hexaminolevulinate, a heme precursor, causes preferential accumulation of protoporphyrin IX and other photoactive porphyrins in neoplastic cells, which are then excited under the wavelength of blue light (~450 nm) to fluoresce red. The sensitivity of BLC in detecting cancerous lesions is much higher than that of white-light alone (91% vs. 76%) and used together, BLC plus WLC has a sensitivity of 98.5%.1 

A recent phase III prospective multicenter study found that 20.6% of bladder malignancies were visualized solely under blue-light and would have been missed with WLC alone, consistent with other prospective BLC trials.2 Compared to standard WLC, BLC increases detection rates of papillary malignancy by 12% and CIS by 43%. In this trial, the improved detection rate and increased accuracy of risk stratification after BLC led to a change in management in 14% of patients who would have been under-staged and under-treated with WLC alone.3 The rate of false positive lesions is comparable between WLC and BLC (approximately 25-30%). In a subset of 13 patients who had recurrent high risk disease that was detected by BLC only, none had positive urine cytology, suggesting that though urinary cytology has high specificity, the sensitivity in high grade diseases may not be sufficient.

BLC has virtually no known toxic effects and patients report decreased anxiety and would recommend it to others.2,4 Following the positive data coming from large clinical trials, the addition of BLC in various settings is currently supported by the American Urological Association-Society of Urologic Oncology and the European Association of Urology.3 Expert recommendations currently support the use of BLC in post-treatment surveillance, as literature has demonstrated a survival benefit and decrease in recurrence rates with its incorporation.1,3

Our experience with this patient suggests an additional role for BLC in the initial diagnosis. There remain unanswered questions regarding the role of BLC in patients with non-muscle invasive BC at high risk for progression to invasive disease. In a recent review of the Cysview registry of over 3,500 lesions from over 1,200 patients, 23% of lesions were only visible under blue light and 14% of these lesions were muscle-invasive and would not have been detected otherwise (unpublished data). Early detection of disease is associated with a decrease in disease morbidity and mortality by increasing the utility of bladder-sparing therapies in non-muscle invasive disease and facilitating earlier delivery of neoadjuvant chemotherapy and radical cystectomy in muscle-invasive disease. This is of particular importance, considering the recurrence rate of non-muscle-invasive bladder cancer is 50-70%, and approximately 10-20% of patients will progress to muscle-invasive disease.5 Enhanced cystoscopic techniques have proven critical for earlier detection and accurate staging of both initial and recurrent cases.

Written by: Nima Nassiri, MD; Marissa Maas, BS; Kian Asanad, MD; Siamak Daneshmand, MD, Institute of Urology. Keck School of Medicine. University of Southern California. Los Angeles, CA

Disclosure: Dr. Daneshmand is a paid consultant for PhotoCure


  1. Daneshmand S, Bazargani ST, Bivalacqua TJ, et al: Blue light cystoscopy for the diagnosis of bladder cancer: Results from the US prospective multicenter registry. Urol. Oncol. 2018; 36: 361.e1-361.e6.
  2. 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; 199: 1158–1165.
  3. Lotan Y, Bivalacqua TJ, Downs T, et al: Blue light flexible cystoscopy with hexaminolevulinate in non-muscle-invasive bladder cancer: review of the clinical evidence and consensus statement on optimal use in the USA - update 2018. Nat. Rev. Urol. 2019; 16: 377–386.
  4. Witjes JA, Gomella LG, Stenzl A, et al: Safety of hexaminolevulinate for blue light cystoscopy in bladder cancer. A combined analysis of the trials used for registration and postmarketing data. Urology 2014; 84: 122–6.
  5. Antoni S, Ferlay J, Soerjomataram I, et al: Bladder Cancer Incidence and Mortality: A Global Overview and Recent Trends. Eur. Urol. 2017; 71: 96–108.

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