Efficacy and Safety of Blue Light Flexible Cystoscopy with Hexaminolevulinate in the Surveillance of Bladder Cancer: A Phase III, Comparative, Multicenter Study

No AccessJournal of UrologyAdult Urology1 May 2018Efficacy and Safety of Blue Light Flexible Cystoscopy with Hexaminolevulinate in the Surveillance of Bladder Cancer: A Phase III, Comparative, Multicenter Studyis corrected byERRATUM Siamak Daneshmand, Sanjay Patel, Yair Lotan, Kamal Pohar, Edouard Trabulsi, Michael Woods, Tracy Downs, William Huang, Jeffrey Jones, Michael O’Donnell, Trinity Bivalacqua, Joel DeCastro, Gary Steinberg, Ashish Kamat, Matthew Resnick, Badrinath Konety, Mark Schoenberg, J. Stephen Jones, and Flexible Blue Light Study Group Collaborators Siamak DaneshmandSiamak Daneshmand University of Southern California, Los Angeles, California More articles by this author , Sanjay PatelSanjay Patel University of Oklahoma, Oklahoma City, Oklahoma More articles by this author , Yair LotanYair Lotan University of Texas Southwestern Medical Center, Dallas, Texas Financial interest and/or other relationship with Photocure. More articles by this author , Kamal PoharKamal Pohar Ohio State University, Columbus, Ohio More articles by this author , Edouard TrabulsiEdouard Trabulsi Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania More articles by this author , Michael WoodsMichael Woods University of North Carolina, Chapel Hill, North Carolina More articles by this author , Tracy DownsTracy Downs University of Wisconsin, Madison, Wisconsin More articles by this author , William HuangWilliam Huang New York University School of Medicine, New York, New York More articles by this author , Jeffrey JonesJeffrey Jones Veterans Affairs Medical Center, Houston, Texas More articles by this author , Michael O’DonnellMichael O’Donnell University of Iowa, Iowa City, Iowa More articles by this author , Trinity BivalacquaTrinity Bivalacqua Johns Hopkins University, Baltimore, Maryland Financial interest and/or other relationship with Photocure. More articles by this author , Joel DeCastroJoel DeCastro Columbia University Medical Center, New York, New York More articles by this author , Gary SteinbergGary Steinberg University of Chicago, Chicago, Illinois Financial interest and/or other relationship with Photocure, Merck, FKD, MDxHealth, Cold Genesys, UroGen, Heat Biologics, Roche, Natera and BioCanCell. More articles by this author , Ashish KamatAshish Kamat University of Texas M. D. Anderson Cancer Center, Houston, Texas More articles by this author , Matthew ResnickMatthew Resnick Vanderbilt University, Nashville, Tennessee More articles by this author , Badrinath KonetyBadrinath Konety University of Minnesota, Minneapolis, Minnesota More articles by this author , Mark SchoenbergMark Schoenberg Montefiore Medical Center, Bronx, New York More articles by this author , J. Stephen JonesJ. Stephen Jones Cleveland Clinic, Cleveland, Ohio More articles by this author , and Flexible Blue Light Study Group Collaborators More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.11.096AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We compared blue light flexible cystoscopy with white light flexible cystoscopy for the detection of bladder cancer during surveillance. Materials and Methods: Patients at high risk for recurrence received hexaminolevulinate intravesically before white light flexible cystoscopy and randomization to blue light flexible cystoscopy. All suspicious lesions were documented. Patients with suspicious lesions were referred to the operating room for repeat white and blue light cystoscopy. All suspected lesions were biopsied or resected and specimens were examined by an independent pathology consensus panel. The primary study end point was the proportion of patients with histologically confirmed malignancy detected only with blue light flexible cystoscopy. Additional end points were the false-positive rate, carcinoma in situ detection and additional tumors detected only with blue light cystoscopy. Results: Following surveillance 103 of the 304 patients were referred, including 63 with confirmed malignancy, of whom 26 had carcinoma in situ. In 13 of the 63 patients (20.6%, 95% CI 11.5–32.7) recurrence was seen only with blue light flexible cystoscopy (p <0.0001). Five of these cases were confirmed as carcinoma in situ. Operating room examination confirmed carcinoma in situ in 26 of 63 patients (41%), which was detected only with blue light cystoscopy in 9 of the 26 (34.6%, 95% CI 17.2–55.7, p <0.0001). Blue light cystoscopy identified additional malignant lesions in 29 of the 63 patients (46%). The false-positive rate was 9.1% for white and blue light cystoscopy. None of the 12 adverse events during surveillance were serious. Conclusions: Office based blue light flexible cystoscopy significantly improves the detection of patients with recurrent bladder cancer and it is safe when used for surveillance. Blue light cystoscopy in the operating room significantly improves the detection of carcinoma in situ and detects lesions that are missed with white light cystoscopy. References 1 : A second-look TUR in T1 transitional cell carcinoma: why?. Eur Urol2004; 45: 539. Google Scholar 2 : 5-Aminolaevulinic acid-induced fluorescence cystoscopy during transurethral resection reduces the risk of recurrence in stage Ta/T1 bladder cancer. BJU Int2005; 96: 798. Google Scholar 3 : Long-term benefit of 5-aminolevulinic acid fluorescence assisted transurethral resection of superficial bladder cancer: 5-year results of a prospective randomized study. J Urol2005; 174: 2129. Link, Google Scholar 4 : Residual tumor discovered in routine second transurethral resection in patients with stage T1 transitional cell carcinoma of the bladder. J Urol1991; 146: 316. Google Scholar 5 : [ALA fluorescent diagnosis of bladder cancer]. Urologiia2000; 5: 48. Google Scholar 6 : The value of secondary transurethral resection for superficial bladder tumors. Akt Urol1994; 25: 208. Google Scholar 7 : The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee. Am J Surg Pathol1998; 22: 1435. Crossref, Medline, Google Scholar 8 : Metabolic characterization of tumor cell-specific protoporphyrin IX accumulation after exposure to 5-aminolevulinic acid in human colonic cells. J Photochem Photobiol B2002; 76: 518. Google Scholar 9 : Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience. J Photochem Photobiol B1990; 6: 143. Crossref, Medline, Google Scholar 10 : A phase III, multicenter comparison of hexaminolevulinate fluorescence cystoscopy and white light cystoscopy for the detection of superficial papillary lesions in patients with bladder cancer. J Urol2007; 178: 62. Link, Google Scholar 11 : Hexaminolevulinate guided fluorescence cystoscopy reduces recurrence in patients with non-muscle invasive bladder cancer. J Urol2010; 184: 1907. Link, Google Scholar 12 : Fluorescence-guided transurethral resection of bladder tumours reduces bladder tumour recurrence due to less residual tumour tissue in Ta/T1 patients: a randomized two-centre study. BJU Int2011; 108: E297. Google Scholar 13 : Hexaminolevulinate fluorescence cystoscopy and transurethral resection of the bladder in noninvasive bladder tumors. J Endourol2009; 23: 977. Google Scholar 14 : Photodynamic diagnosis of non-muscle invasive bladder cancer using hexaminolevulinic acid. Rom J Morphol Embryol2011; 52: 123. Google Scholar 15 : A comparison of hexaminolevulinate fluorescence cystoscopy and white light cystoscopy for the detection of carcinoma in situ in patients with bladder cancer: a phase III, multicenter study. J Urol2007; 178: 68. Link, Google Scholar 16 : Long-term reduction in bladder cancer recurrence with hexaminolevulinate enabled fluorescence cystoscopy. J Urol2012; 188: 58. Link, Google Scholar 17 : Hexyl aminolevulinate-guided fluorescence cystoscopy in the diagnosis and follow-up of patients with non-muscle-invasive bladder cancer: a critical review of the current literature. Eur Urol2013; 64: 624. Google Scholar 18 : Photodynamic diagnosis of non-muscle-invasive bladder cancer with hexaminolevulinate cystoscopy: a meta-analysis of detection and recurrence based on raw data. Eur Urol2013; 64: 846. Google Scholar 19 : Clinical and cost effectiveness of hexaminolevulinate-guided blue light cystoscopy: evidence review and updated expert recommendations. Eur Urol2014; 66: 863. Google Scholar 20 : The cost-effectiveness of blue light cystoscopy in bladder cancer detection: United States projections based on clinical data showing 4.5 years of follow up after a single hexaminolevulinate hydrochloride instillation. Can J Urol2013; 20: 6682. Google Scholar 21 : World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon: IARC2004. Google Scholar 22 : AJCC Cancer Staging Handbook, 7th ed. New York: Springer2010. Google Scholar 23 : Flexible cystoscopy assisted by hexaminolevulinate induced fluorescence: a new approach for bladder cancer detection and surveillance?. Eur Urol2005; 47: 323. Google Scholar 24 : Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Joint Guideline, 2016. Available at https://www.auanet.org/education/guidelines/non-muscle-invasive-bladder-cancer.cfm. Accessed November 1, 2017. Google Scholar 25 : Hexaminolevulinate blue-light cystoscopy in non-muscle-invasive bladder cancer: review of the clinical evidence and consensus statement on appropriate use in the USA. Nat Rev Urol2014; 11: 589. Google Scholar 26 : Safety of hexaminolevulinate for blue light cystoscopy in bladder cancer. A combined analysis of the trials used for registration and postmarketing data. Urology2014; 84: 122. Google Scholar © 2018 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byChappidi M, Yang H, Meng M, Bivalacqua T, Daneshmand S, Holzbeierlein J, Kaimakliotis H, Konety B, Liao J, Pohar K, Steinberg G, Taylor J, Tyson M, Willard B, Lotan Y, Porten S and Kates M (2021) Utility of Blue Light Cystoscopy for Post-bacillus Calmette-Guérin Bladder Cancer Recurrence Detection: Implications for Clinical Trial Recruitment and Study ComparisonsJournal of Urology, VOL. 207, NO. 3, (534-540), Online publication date: 1-Mar-2022.Barocas D, Boorjian S, Alvarez R, Downs T, Gross C, Hamilton B, Kobashi K, Lipman R, Lotan Y, Ng C, Nielsen M, Peterson A, Raman J, Smith-Bindman R and Souter L (2020) Microhematuria: AUA/SUFU GuidelineJournal of Urology, VOL. 204, NO. 4, (778-786), Online publication date: 1-Oct-2020.Related articlesJournal of Urology8 Apr 2019ERRATUM Volume 199Issue 5May 2018Page: 1158-1165 Advertisement Copyright & Permissions© 2018 by American Urological Association Education and Research, Inc.Keywordsneoplasm recurrencelocaloptical imagingcystoscopycarcinoma in situbladder neoplasmsAcknowledgmentsJude Douglass, Healthcom Partners Ltd, Oxford, United Kingdom, assisted with writing and editing.MetricsAuthor Information Siamak Daneshmand University of Southern California, Los Angeles, California More articles by this author Sanjay Patel University of Oklahoma, Oklahoma City, Oklahoma More articles by this author Yair Lotan University of Texas Southwestern Medical Center, Dallas, Texas Financial interest and/or other relationship with Photocure. More articles by this author Kamal Pohar Ohio State University, Columbus, Ohio More articles by this author Edouard Trabulsi Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania More articles by this author Michael Woods University of North Carolina, Chapel Hill, North Carolina More articles by this author Tracy Downs University of Wisconsin, Madison, Wisconsin More articles by this author William Huang New York University School of Medicine, New York, New York More articles by this author Jeffrey Jones Veterans Affairs Medical Center, Houston, Texas More articles by this author Michael O’Donnell University of Iowa, Iowa City, Iowa More articles by this author Trinity Bivalacqua Johns Hopkins University, Baltimore, Maryland Financial interest and/or other relationship with Photocure. More articles by this author Joel DeCastro Columbia University Medical Center, New York, New York More articles by this author Gary Steinberg University of Chicago, Chicago, Illinois Financial interest and/or other relationship with Photocure, Merck, FKD, MDxHealth, Cold Genesys, UroGen, Heat Biologics, Roche, Natera and BioCanCell. More articles by this author Ashish Kamat University of Texas M. D. Anderson Cancer Center, Houston, Texas More articles by this author Matthew Resnick Vanderbilt University, Nashville, Tennessee More articles by this author Badrinath Konety University of Minnesota, Minneapolis, Minnesota More articles by this author Mark Schoenberg Montefiore Medical Center, Bronx, New York More articles by this author J. Stephen Jones Cleveland Clinic, Cleveland, Ohio More articles by this author Flexible Blue Light Study Group Collaborators More articles by this author Expand All Advertisement PDF downloadLoading ...