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Results of a prospective randomized study assessing the efficacy of fluorescent cystoscopy-assisted transurethral resection and single instillation of doxorubicin in patients with non-muscle-invasive bladder cancer

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World Journal of Urology Aims and scope Submit manuscript



To assess the efficacy of two treatment options for non-muscle-invasive bladder cancer (NMIBC): (1) transurethral resection (TUR) guided by fluorescence cystoscopy (FC) with the use of 5-aminolevulinic acid (5-ALA) and (2) single early instillation of doxorubicin in a single-center open-label prospective randomized study with a 2 × 2 factorial design.

Patients and methods

Patients with clinical suspicion of primary or recurrent NMIBC were randomized into four study arms: FC-assisted TUR with 5-ALA and single instillation of doxorubicin, FC-assisted TUR without instillation, TUR in white light (WL) with single instillation of doxorubicin, and WL-TUR only. The study was designed to assess recurrence-free survival in arms with and without any of two interventions.


Of 525 patients included, 377 (72 %) were eligible for primary outcome assessment. The median follow-up was 54.8 months. FC statistically significantly decreased the risk of disease recurrence and progression with hazard ratio (HR) 0.56 (95 % CI 0.39–0.80, p = 0.001) and 0.33 (95 % CI 0.12–0.91, p = 0.031), respectively. The HRs for recurrence and progression for single instillation of doxorubicin were 0.76 (95 % CI 0.54–1.07, p = 0.11) and 0.65 (95 % CI 0.28–1.52, p = 0.32), respectively. The overall and cancer-specific survival rates did not differ significantly based on the therapeutic interventions.


In patients with NMIBC, FC-assisted TUR with 5-ALA results in a substantial recurrence and progression risk reduction as compared to WL-TUR. The single early postoperative instillation of doxorubicin did not have a statistically significant impact on recurrence and progression risks.

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  1. Heney NM (1992) Natural history of superficial bladder cancer. Prognostic features and long-term disease course. Urol Clin North Am 19:429–433

    CAS  PubMed  Google Scholar 

  2. Brausi M, Collette L, Kurth K et al (2002) Variability in the recurrence rate at first follow-up cystoscopy after TUR in stage Ta T1 transitional cell carcinoma of the bladder: a combined analysis of seven EORTC studies. Eur Urol 41:523–531

    Article  PubMed  Google Scholar 

  3. Kaasinen E, Rintala E, Hellström P et al (2002) Factors explaining recurrence in patients undergoing chemoimmunotherapy regimens for frequently recurring superficial bladder carcinoma. Eur Urol 42:167–174

    Article  PubMed  Google Scholar 

  4. Burger M, Grossman HB, Droller M et al (2013) Photodynamic diagnosis of non-muscle-invasive bladder cancer with hexaminolevulinate cystoscopy: a meta-analysis of detection and recurrence based on raw data. Eur Urol 64:846–854

    Article  PubMed  Google Scholar 

  5. Abern MR, Owusu RA, Anderson MR, Rampersaud EN, Inman BA (2013) Perioperative intravesical chemotherapy in non-muscle-invasive bladder cancer: a systematic review and meta-analysis. J Natl Compr Cancer Netw 11:477–484

    CAS  Google Scholar 

  6. Perlis N, Zlotta AR, Beyene J, Finelli A, Fleshner NE, Kulkarni GS (2013) Immediate post-transurethral resection of bladder tumor intravesical chemotherapy prevents non-muscle-invasive bladder cancer recurrences: an updated meta-analysis on 2548 patients and quality-of-evidence review. Eur Urol 64:421–430

    Article  PubMed  Google Scholar 

  7. Berrum-Svennung I, Granfors T, Jahnson S, Boman H, Holmäng S (2008) A single instillation of epirubicin after transurethral resection of bladder tumors prevents only small recurrences. J Urol 179:101–105

    Article  PubMed  Google Scholar 

  8. Stenzl A, Penkoff H, Dajc-Sommerer E et al (2011) Detection and clinical outcome of urinary bladder cancer with 5-aminolevulinic acid-induced fluorescence cystoscopy: a multicenter randomized, double-blind, placebo-controlled trial. Cancer 117:938–947

    Article  PubMed  Google Scholar 

  9. O’Brien T, Ray E, Chatterton K, Khan MS, Chandra A, Thomas K (2013) Prospective randomized trial of hexylaminolevulinate photodynamic-assisted transurethral resection of bladder tumour (TURBT) plus single-shot intravesical mitomycin C vs conventional white-light TURBT plus mitomycin C in newly presenting non-muscle-invasive bladder cancer. BJU Int 112:1096–1104

    Article  PubMed  Google Scholar 

  10. Cordeiro ER, Anastasiadis A, Bus MT, Alivizatos G, de la Rosette JJ, de Reijke TM (2013) Is photodynamic diagnosis ready for introduction in urological clinical practice? Expert Rev Anticancer Ther 13:669–680

    Article  CAS  PubMed  Google Scholar 

  11. Sylvester RJ, van der Meijden AP, Oosterlinck W et al (2006) Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol 49:466–475

    Article  PubMed  Google Scholar 

  12. Burger M, Stief CG, Zaak D et al (2009) Hexaminolevulinate is equal to 5-aminolevulinic acid concerning residual tumor and recurrence rate following photodynamic diagnostic assisted transurethral resection of bladder tumors. Urology 74:1282–1286

    Article  PubMed  Google Scholar 

  13. Mowatt G, N’Dow J, Vale L et al (2011) Photodynamic diagnosis of bladder cancer compared with white light cystoscopy: systematic review and meta-analysis. Int J Technol Assess Health Care 27:3–10

    Article  PubMed  Google Scholar 

  14. Daniltchenko DI, Riedl CR, Sachs MD et al (2005) Long-term benefit of 5-aminolevulinic acid fluorescence assisted transurethral resection of superficial bladder cancer: 5-year results of a prospective randomized study. J Urol 174:2129–2133

    Article  CAS  PubMed  Google Scholar 

  15. Babjuk M, Soukup V, Petrík R, Jirsa M, Dvorácek J (2005) 5-aminolaevulinic acid-induced fluorescence cystoscopy during transurethral resection reduces the risk of recurrence in stage Ta/T1 bladder cancer. BJU Int 96:798–802

    Article  CAS  PubMed  Google Scholar 

  16. Denzinger S, Burger M, Walter B et al (2007) Clinically relevant reduction in risk of recurrence of superficial bladder cancer using 5-aminolevulinic acid-induced fluorescence diagnosis: 8-year results of prospective randomized study. Urology 69:675–679

    Article  PubMed  Google Scholar 

  17. Schumacher MC, Holmäng S, Davidsson T, Friedrich B, Pedersen J, Wiklund NP (2010) Transurethral resection of non-muscle-invasive bladder transitional cell cancers with or without 5-aminolevulinic Acid under visible and fluorescent light: results of a prospective, randomised, multicentre study. Eur Urol 57:293–299

    Article  CAS  PubMed  Google Scholar 

  18. Kamat AM, Cookson M, Witjes JA, Stenzl A, Grossman HB (2016) The impact of blue light cystoscopy with hexaminolevulinate (HAL) on progression of bladder cancer—a new analysis. Bl Cancer 2:273–278

    Article  PubMed  PubMed Central  Google Scholar 

  19. Lamm D, Persad R, Brausi M et al (2014) Defining progression in nonmuscle invasive bladder cancer: it is time for a new, standard definition. J Urol 191:20–27

    Article  PubMed  Google Scholar 

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The authors thank Ludmila Mirilenka, for her assistance in statistical analysis.


This study was funded by Belarusian Ministry of Health.

Authors’ contribution

AI Rolevich contributed to protocol development, data collection, data analysis, and manuscript writing; AG Zhegalik, AA Mokhort, AA Minich, and VYu Vasilevich collected the data; SL Polyakov contributed to data collection, data analysis, and manuscript writing; SA Krasny and OG Sukonko developed the protocol and edited the manuscript editing.

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Correspondence to Alexander I. Rolevich.

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The authors declare that they have no conflict of interest related to this study.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Rolevich, A.I., Zhegalik, A.G., Mokhort, A.A. et al. Results of a prospective randomized study assessing the efficacy of fluorescent cystoscopy-assisted transurethral resection and single instillation of doxorubicin in patients with non-muscle-invasive bladder cancer. World J Urol 35, 745–752 (2017).

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