hexaminolevulinate Evidence: Trial Results and Peer-Reviewed Publications

Hipa.ai Research · Source: PubMed & ClinicalTrials.gov / AACT · Last updated:

The clinical evidence base for hexaminolevulinate comprises 32 peer-reviewed publications across 15 journals, 2 pivotal-trial primary-outcome rows reported to ClinicalTrials.gov, spanning indications including Non-Muscle Invasive Bladder Neoplasms, Urinary Bladder Neoplasms, and Colonic Neoplasms. Most recent publication: VI-RADS followed by Photodynamic Transurethral Resection of Non-Muscle-Invasive Bladder Cancer vs White-Light Conventional and Second-resection: the 'CUT-less' Randomised Trial Protocol., BJU Int, 2025.

Top peer-reviewed publications

Curated set of pivotal-trial result papers and recent publications in high-tier journals.

  1. Association of smoking status and recurrence of non-muscle invasive bladder cancer among patients managed with blue light cystoscopy.
    Matulewicz RS, Ravvaz K, Weissert JA, et al. · Urol Oncol · 2022
    PubMed: PMID 34053856 · NCT02660645 (BLCCR) · Urinary Bladder Neoplasms
  2. Racial Differences in the Detection Rate of Bladder Cancer Using Blue Light Cystoscopy: Insights from a Multicenter Registry.
    Ladi-Seyedian SS, Ghoreifi A, Konety B, et al. · Cancers (Basel) · 2024
    PubMed: PMID 38610946 · NCT02660645 (BLCCR) · Urinary Bladder Neoplasms
  3. Technical Considerations to Minimize False-Positive Findings in Blue Light Cystoscopy for Nonmuscle-Invasive Bladder Cancer.
    Ghoreifi A, Daneshmand S · J Urol · 2024
    PubMed: PMID 39284074 · NCT02660645 (BLCCR) · Urinary Bladder Neoplasms
  4. Efficacy and Safety of Blue Light Flexible Cystoscopy with Hexaminolevulinate in the Surveillance of Bladder Cancer: A Phase III, Comparative, Multicenter Study.
    Daneshmand S, Patel S, Lotan Y, et al. · J Urol · 2019
    PubMed: PMID 29203268 · NCT02660645 (BLCCR) · Urinary Bladder Neoplasms
  5. Blue light cystoscopy for the diagnosis of bladder cancer: Results from the US prospective multicenter registry.
    Daneshmand S, Bazargani ST, Bivalacqua TJ, et al. · Urol Oncol · 2018
    PubMed: PMID 29859728 · NCT02660645 (BLCCR) · Urinary Bladder Neoplasms
  6. Utility of Blue Light Cystoscopy for Post-bacillus Calmette-Guérin Bladder Cancer Recurrence Detection: Implications for Clinical Trial Recruitment and Study Comparisons.
    Chappidi MR, Yang H, Meng MV, et al. · J Urol · 2022
    PubMed: PMID 34694916 · NCT02660645 (BLCCR) · Urinary Bladder Neoplasms
  7. Is a restaging TURBT necessary in high-risk NMIBC if the initial TURBT was performed with blue light?
    Alsyouf M, Ladi-Seyedian SS, Konety B, et al. · Urol Oncol · 2023
    PubMed: PMID 36435710 · NCT02660645 (BLCCR) · Urinary Bladder Neoplasms
  8. Role of blue-light cystoscopy in detecting invasive bladder tumours: data from a multi-institutional registry.
    Ahmadi H, Ladi-Seyedian SS, Konety B, et al. · BJU Int · 2022
    PubMed: PMID 34637596 · NCT02660645 (BLCCR) · Urinary Bladder Neoplasms

Primary-outcome results across pivotal trials

Per-arm reported values from Phase 2/3 and Phase 3 trials with results posted to ClinicalTrials.gov.

TrialIndicationPrimary endpointArmValue
NCT02560584Urinary Bladder NeoplasmsProportion of Patients With Histologically Confirmed Malignancy Where Malignancy is Only Detected With Blue Light Cystoscopy With Cysview and Not White Light Cystoscopy
At time of cystoscopy procedure
Cysview Arm13 Participants
NCT05600322Urinary Bladder NeoplasmsNumber of Patients With Histology-confirmed Lesions (Ta, T1, or CIS) Who Have at Least One Such Lesion Found by Hexvix Blue Light Cystoscopy But Not by White Light Cystoscopy.
1 day (At time of cystoscopy examination)
Hexvix Blue Light Cystoscopy42 Participants

Publications by year

1998–2025: 32 publications.

1998
1
2002
1
2006
1
2008
1
2010
2
2011
1
2013
1
2014
1
2015
3
2016
2
2017
2
2018
1
2019
4
2021
1
2022
6
2023
1
2024
2
2025
1

Publications by indication

Non-Muscle Invasive Bladder Neoplasms (21)

  • VI-RADS followed by Photodynamic Transurethral Resection of Non-Muscle-Invasive Bladder Cancer vs White-Light Conventional and Second-resection: the 'CUT-less' Randomised Trial Protocol.
    BJU Int · 2025 · PMID 39397266 · NCT05962541
  • Bladder cancer prospective cohort study on high-risk non-muscle invasive bladder cancer after photodynamic diagnosis-assisted transurethral resection of the bladder tumor (BRIGHT study).
    Int J Urol · 2022 · PMID 35293022 · NCT05962541
  • European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (Ta, T1, and Carcinoma in Situ).
    Eur Urol · 2022 · PMID 34511303 · NCT05962541
  • The Comprehensive Complication Index for Advanced Monitoring of Complications Following Endoscopic Surgery of the Lower Urinary Tract.
    J Endourol · 2021 · PMID 33222525 · NCT05962541
  • Role of Restaging Transurethral Resection for T1 Non-muscle invasive Bladder Cancer: A Systematic Review and Meta-analysis.
    Eur Urol Focus · 2019 · PMID 28753839 · NCT05962541

Urinary Bladder Neoplasms (10)

  • Racial Differences in the Detection Rate of Bladder Cancer Using Blue Light Cystoscopy: Insights from a Multicenter Registry.
    Cancers (Basel) · 2024 · PMID 38610946 · NCT02660645
  • Technical Considerations to Minimize False-Positive Findings in Blue Light Cystoscopy for Nonmuscle-Invasive Bladder Cancer.
    J Urol · 2024 · PMID 39284074 · NCT02660645
  • Is a restaging TURBT necessary in high-risk NMIBC if the initial TURBT was performed with blue light?
    Urol Oncol · 2023 · PMID 36435710 · NCT02660645
  • Association of smoking status and recurrence of non-muscle invasive bladder cancer among patients managed with blue light cystoscopy.
    Urol Oncol · 2022 · PMID 34053856 · NCT02660645
  • Utility of Blue Light Cystoscopy for Post-bacillus Calmette-Guérin Bladder Cancer Recurrence Detection: Implications for Clinical Trial Recruitment and Study Comparisons.
    J Urol · 2022 · PMID 34694916 · NCT02660645

Colonic Neoplasms (1)

  • Early detection of premalignant conditions in the colon by fluorescence endoscopy using local sensitization with hexaminolevulinate.
    Endoscopy · 2008 · PMID 18197583 · NCT01344902

Publications by journal

Trial-results highlights

Clinical trials have investigated hexaminolevulinate, which is marketed under brand names such as Cysview and Hexvix. This agent is used to enhance the visualization of bladder tissue during cystoscopy procedures for patients with urinary bladder neoplasms. These studies aimed to identify bladder malignancies or lesions that might otherwise be missed by standard diagnostic methods, specifically focusing on findings detected only with blue light cystoscopy when hexaminolevulinate was used, and not with white light cystoscopy alone.

In the NCT02560584 study, the primary outcome measured the proportion of patients with histologically confirmed malignancy where the malignancy was exclusively detected using blue light cystoscopy with Cysview, and not by white light cystoscopy. At the time of the cystoscopy procedure, this specific finding was observed in 13 participants in the Cysview arm. Another pivotal trial, NCT05600322, evaluated the number of patients with histology-confirmed lesions—specifically Ta, T1, or CIS lesions—that were found by Hexvix blue light cystoscopy but were not detected by white light cystoscopy. In the Hexvix Blue Light Cystoscopy arm, 42 participants had at least one such lesion identified. This assessment was conducted one day following the cystoscopy examination.

All values presented are sourced from primary registry reporting. For clinical decisions, individual study papers should be consulted.

All hexaminolevulinate publications (32)

2025 (1 paper)

  1. VI-RADS followed by Photodynamic Transurethral Resection of Non-Muscle-Invasive Bladder Cancer vs White-Light Conventional and Second-resection: the 'CUT-less' Randomised Trial Protocol.
    Del Giudice F, Vestri A, Fegatelli DA, et al. · BJU Int · 2025 · Derived
    PubMed: PMID 39397266 · NCT05962541 (CUT-less) · Non-Muscle Invasive Bladder Neoplasms

2024 (2 papers)

  1. Racial Differences in the Detection Rate of Bladder Cancer Using Blue Light Cystoscopy: Insights from a Multicenter Registry.
    Ladi-Seyedian SS, Ghoreifi A, Konety B, et al. · Cancers (Basel) · 2024 · Trial result
    PubMed: PMID 38610946 · NCT02660645 (BLCCR) · Urinary Bladder Neoplasms
  2. Technical Considerations to Minimize False-Positive Findings in Blue Light Cystoscopy for Nonmuscle-Invasive Bladder Cancer.
    Ghoreifi A, Daneshmand S · J Urol · 2024 · Trial result
    PubMed: PMID 39284074 · NCT02660645 (BLCCR) · Urinary Bladder Neoplasms

2023 (1 paper)

  1. Is a restaging TURBT necessary in high-risk NMIBC if the initial TURBT was performed with blue light?
    Alsyouf M, Ladi-Seyedian SS, Konety B, et al. · Urol Oncol · 2023 · Trial result
    PubMed: PMID 36435710 · NCT02660645 (BLCCR) · Urinary Bladder Neoplasms

2022 (6 papers)

  1. Association of smoking status and recurrence of non-muscle invasive bladder cancer among patients managed with blue light cystoscopy.
    Matulewicz RS, Ravvaz K, Weissert JA, et al. · Urol Oncol · 2022 · Trial result
    PubMed: PMID 34053856 · NCT02660645 (BLCCR) · Urinary Bladder Neoplasms
  2. Utility of Blue Light Cystoscopy for Post-bacillus Calmette-Guérin Bladder Cancer Recurrence Detection: Implications for Clinical Trial Recruitment and Study Comparisons.
    Chappidi MR, Yang H, Meng MV, et al. · J Urol · 2022 · Trial result
    PubMed: PMID 34694916 · NCT02660645 (BLCCR) · Urinary Bladder Neoplasms
  3. Role of blue-light cystoscopy in detecting invasive bladder tumours: data from a multi-institutional registry.
    Ahmadi H, Ladi-Seyedian SS, Konety B, et al. · BJU Int · 2022 · Trial result
    PubMed: PMID 34637596 · NCT02660645 (BLCCR) · Urinary Bladder Neoplasms
  4. Safety of repeat blue light cystoscopy with hexaminolevulinate (HAL) in the management of bladder cancer: Results from a phase III, comparative, multi-center study.
    Pohar KS, Patel S, Lotan Y, et al. · Urol Oncol · 2022 · Derived
    PubMed: PMID 35750559 · NCT02560584 · Urinary Bladder Neoplasms
  5. Bladder cancer prospective cohort study on high-risk non-muscle invasive bladder cancer after photodynamic diagnosis-assisted transurethral resection of the bladder tumor (BRIGHT study).
    Kobayashi K, Matsuyama H, Kawai T, et al. · Int J Urol · 2022 · Background
    PubMed: PMID 35293022 · NCT05962541 (CUT-less) · Non-Muscle Invasive Bladder Neoplasms
  6. European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (Ta, T1, and Carcinoma in Situ).
    Babjuk M, Burger M, Capoun O, et al. · Eur Urol · 2022 · Background
    PubMed: PMID 34511303 · NCT05962541 (CUT-less) · Non-Muscle Invasive Bladder Neoplasms

2021 (1 paper)

  1. The Comprehensive Complication Index for Advanced Monitoring of Complications Following Endoscopic Surgery of the Lower Urinary Tract.
    Waldbillig F, Nientiedt M, Kowalewski KF, et al. · J Endourol · 2021 · Background
    PubMed: PMID 33222525 · NCT05962541 (CUT-less) · Non-Muscle Invasive Bladder Neoplasms

2019 (4 papers)

  1. Efficacy and Safety of Blue Light Flexible Cystoscopy with Hexaminolevulinate in the Surveillance of Bladder Cancer: A Phase III, Comparative, Multicenter Study.
    Daneshmand S, Patel S, Lotan Y, et al. · J Urol · 2019 · Trial result
    PubMed: PMID 29203268 · NCT02660645 (BLCCR) · Urinary Bladder Neoplasms
  2. Patient-reported outcomes of blue-light flexible cystoscopy with hexaminolevulinate in the surveillance of bladder cancer: results from a prospective multicentre study.
    Smith AB, Daneshmand S, Patel S, et al. · BJU Int · 2019 · Derived
    PubMed: PMID 29979488 · NCT02560584 · Urinary Bladder Neoplasms
  3. Role of Restaging Transurethral Resection for T1 Non-muscle invasive Bladder Cancer: A Systematic Review and Meta-analysis.
    Naselli A, Hurle R, Paparella S, et al. · Eur Urol Focus · 2019 · Background
    PubMed: PMID 28753839 · NCT05962541 (CUT-less) · Non-Muscle Invasive Bladder Neoplasms
  4. Repeat Transurethral Resection in Non-muscle-invasive Bladder Cancer: A Systematic Review.
    Cumberbatch MGK, Foerster B, Catto JWF, et al. · Eur Urol · 2019 · Background
    PubMed: PMID 29523366 · NCT05962541 (CUT-less) · Non-Muscle Invasive Bladder Neoplasms

2018 (1 paper)

  1. Blue light cystoscopy for the diagnosis of bladder cancer: Results from the US prospective multicenter registry.
    Daneshmand S, Bazargani ST, Bivalacqua TJ, et al. · Urol Oncol · 2018 · Trial result
    PubMed: PMID 29859728 · NCT02660645 (BLCCR) · Urinary Bladder Neoplasms

2017 (2 papers)

  1. Definitions, End Points, and Clinical Trial Designs for Non-Muscle-Invasive Bladder Cancer: Recommendations From the International Bladder Cancer Group.
    Kamat AM, Sylvester RJ, Böhle A, et al. · J Clin Oncol · 2017 · Background
    PubMed: PMID 26811532 · NCT05962541 (CUT-less) · Non-Muscle Invasive Bladder Neoplasms
  2. The impact of re-transurethral resection on clinical outcomes in a large multicentre cohort of patients with T1 high-grade/Grade 3 bladder cancer treated with bacille Calmette-Guérin.
    Gontero P, Sylvester R, Pisano F, et al. · BJU Int · 2017 · Background
    PubMed: PMID 26469362 · NCT05962541 (CUT-less) · Non-Muscle Invasive Bladder Neoplasms

2016 (2 papers)

  1. Economic Burden of Bladder Cancer Across the European Union.
    Leal J, Luengo-Fernandez R, Sullivan R, et al. · Eur Urol · 2016 · Background
    PubMed: PMID 26508308 · NCT05962541 (CUT-less) · Non-Muscle Invasive Bladder Neoplasms
  2. EORTC Nomograms and Risk Groups for Predicting Recurrence, Progression, and Disease-specific and Overall Survival in Non-Muscle-invasive Stage Ta-T1 Urothelial Bladder Cancer Patients Treated with 1-3 Years of Maintenance Bacillus Calmette-Guérin.
    Cambier S, Sylvester RJ, Collette L, et al. · Eur Urol · 2016 · Background
    PubMed: PMID 26210894 · NCT05962541 (CUT-less) · Non-Muscle Invasive Bladder Neoplasms

2015 (3 papers)

  1. The economics of bladder cancer: costs and considerations of caring for this disease.
    Svatek RS, Hollenbeck BK, Holmäng S, et al. · Eur Urol · 2015 · Background
    PubMed: PMID 24472711 · NCT05962541 (CUT-less) · Non-Muscle Invasive Bladder Neoplasms
  2. Clinical significance of definite muscle layer in TUR specimen for evaluating progression rate in T1G3 bladder cancer: multicenter retrospective study by the Sapporo Medical University Urologic Oncology Consortium (SUOC).
    Shindo T, Masumori N, Kitamura H, et al. · World J Urol · 2015 · Background
    PubMed: PMID 24190368 · NCT05962541 (CUT-less) · Non-Muscle Invasive Bladder Neoplasms
  3. Second transurethral resection and prognosis of high-grade non-muscle invasive bladder cancer in patients not receiving bacillus Calmette-Guérin.
    Angulo JC, Palou J, García-Tello A, et al. · Actas Urol Esp · 2015 · Background
    PubMed: PMID 24613147 · NCT05962541 (CUT-less) · Non-Muscle Invasive Bladder Neoplasms

2014 (1 paper)

  1. 5-Year outcome of a randomized prospective study comparing bacillus Calmette-Guérin with epirubicin and interferon-α2b in patients with T1 bladder cancer.
    Hemdan T, Johansson R, Jahnson S, et al. · J Urol · 2014 · Background
    PubMed: PMID 24231843 · NCT05962541 (CUT-less) · Non-Muscle Invasive Bladder Neoplasms

2013 (1 paper)

  1. Final results of an EORTC-GU cancers group randomized study of maintenance bacillus Calmette-Guérin in intermediate- and high-risk Ta, T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus 3 years of maintenance.
    Oddens J, Brausi M, Sylvester R, et al. · Eur Urol · 2013 · Background
    PubMed: PMID 23141049 · NCT05962541 (CUT-less) · Non-Muscle Invasive Bladder Neoplasms

2011 (1 paper)

  1. Detrusor muscle in the first, apparently complete transurethral resection of bladder tumour specimen is a surrogate marker of resection quality, predicts risk of early recurrence, and is dependent on operator experience.
    Mariappan P, Zachou A, Grigor KM, et al. · Eur Urol · 2011 · Background
    PubMed: PMID 19524354 · NCT05962541 (CUT-less) · Non-Muscle Invasive Bladder Neoplasms

2010 (2 papers)

  1. Patterns of care for early stage bladder cancer.
    Strope SA, Ye Z, Hollingsworth JM, et al. · Cancer · 2010 · Background
    PubMed: PMID 20310051 · NCT05962541 (CUT-less) · Non-Muscle Invasive Bladder Neoplasms
  2. Regional differences in early stage bladder cancer care and outcomes.
    Skolarus TA, Ye Z, Zhang S, et al. · Urology · 2010 · Background
    PubMed: PMID 20394976 · NCT05962541 (CUT-less) · Non-Muscle Invasive Bladder Neoplasms

2008 (1 paper)

  1. Early detection of premalignant conditions in the colon by fluorescence endoscopy using local sensitization with hexaminolevulinate.
    Mayinger B, Neumann F, Kastner C, et al. · Endoscopy · 2008 · Trial result
    PubMed: PMID 18197583 · NCT01344902 · Colonic Neoplasms

2006 (1 paper)

  1. Transurethral bladder tumor resection: intraoperative and postoperative complications in a residency setting.
    Nieder AM, Meinbach DS, Kim SS, et al. · J Urol · 2006 · Background
    PubMed: PMID 16280830 · NCT05962541 (CUT-less) · Non-Muscle Invasive Bladder Neoplasms

2002 (1 paper)

  1. 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.
    Brausi M, Collette L, Kurth K, et al. · Eur Urol · 2002 · Background
    PubMed: PMID 12074794 · NCT05962541 (CUT-less) · Non-Muscle Invasive Bladder Neoplasms

1998 (1 paper)

  1. The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee.
    Epstein JI, Amin MB, Reuter VR, et al. · Am J Surg Pathol · 1998 · Background
    PubMed: PMID 9850170 · NCT05962541 (CUT-less) · Non-Muscle Invasive Bladder Neoplasms

Sources and methodology

This page summarizes published evidence for general reference and does not constitute medical advice. For clinical decisions, consult the linked primary publications and your healthcare provider. Data sourced from PubMed and the ClinicalTrials.gov / AACT database maintained by the Clinical Trials Transformation Initiative (CTTI).