IBCN 2022: The Impact of Blue Light Cystoscopy Use Among Non-Muscle Invasive Bladder Cancer Patients in an Equal Access Setting: Implications on Recurrence and Time to Recurrence by Race

(UroToday.com) Bladder Cancer is the 6th most common type of cancer in the United States and is estimated that there will be 81,180 new cases with approximately 17,100 dying of this disease in 2022.1  Of newly diagnosed bladder cancer cases, approximately 75% are non-muscle-invasive bladder cancer (NMIBC).1  Racial disparity have been previously described with Blacks noted to have worse bladder cancer-specific survival and are associated with up to a 2-fold increase of bladder cancer-specific death when compared to Whites.2-6  Against this backdrop, and as new technologies emerge to diagnose and treat bladder cancer, it is critical to understand implementation taking into account disparities in treatments and outcomes.


Since its introduction in 2004, Blue Light Cystoscopy (BLC) has become an important clinical procedure for bladder cancer management, especially as research suggests that BLC can reduce recurrence rates compared to White Light Cystoscopy (WLC).7-9  However, there is currently a lack of real-world data evaluating the risk of bladder cancer recurrence and progression in an equal access setting, and by race, among those treated with BLC. Some evidence suggests that WLC can fail to detect cases of non-muscle invasive bladder cancer (NMIBC) as compared to BLC, with those tumors that remain unidentified potentially able to progress to a higher stage and lead to more aggressive interventions, including chemotherapy and need for cystectomy.10,11  Thus, less effective surveillance using WLC alone may result in missed diagnoses and thus progressive disease, ultimately leading to inferior oncologic outcomes. The primary objective of this study presented at the IBCN was to assess the impact of BLC with Cysview on recurrence and progression in an equal access setting by race.

A total of 378 NMIBC patients within the Veterans Affairs system that underwent BLC with previous history of WLC from January 1, 2018 to December 31, 2020 were assessed. They determined recurrence rates and time to recurrence prior to BLC (i.e. after previous WLC) and following the BLC. They used the Kaplan-Meier method to estimate event-free survival and Cox regression to determine the association between race and recurrence, progression, and overall survival.

Of 378 patients with complete data; 43 (11%) were Black and 300 (79%) White. Median follow-up was 40.7 months. There were 194 (51%) patients with either T1 HG or T1 without CIS; 52 (14%) had CIS with or without TaHG or T1; and 127 (34%) had TaLG only. A total of 239 (63%) patients received BCG. Median time to first recurrence following BLC was longer compared prior to WLC (40 (33-NE) vs. 26 (17-39) months). The risk of recurrence was significantly lower following BLC (Hazard Ratio (HR) 0.70; 95% Confidence Interval (CI) 0.54-0.90). There was no significant difference in recurrence (Hazard Ratio (HR) 0.83; 95% Confidence Interval (CI) 0.48-1.43), progression (HR 1.46; 95% CI 0.45-4.74), and overall survival (HR 0.69; 95% CI 0.29-1.65) following BLC by Black vs. White race.

In conclusion, this study from an equal access setting in the VA, they observed significantly decreased risk of recurrence and prolonged time interval to recurrence following BLC compared to the pre-study WLC. There was no difference in any bladder cancer outcomes by race.

It has been well established that accessibility of healthcare services is an important driver of bladder cancer outcomes. Cole et al. found that differences in survival for black and white bladder cancer patients was due to disparities in access and treatment.12  In an equal-access setting, our study found that patients were at lower risk of developing recurrence in their bladder cancer following BLC than following WLC alone. Previous studies have shown better quality of cancer care in the VA comparted to the private sector.13  As well, further research found no differences in complications or readmissions by race or SES among patients in equal-access settings.14,15  Taken together, these findings suggest that equal-access systems may improve access to cancer care thereby possibly negating differences in outcomes by other social determinants in population-level data.13 


This study presented at the IBCN has several notable findings. First, they describe BLC use in the largest equal access healthcare system in the US for the first time: the VA. Since its FDA approval in 2010, BLC is increasingly utilized clinically as it improves the detection rate of NMIBC by up to 43%.16,17  This is especially important because WLC alone can fail to detect up to 20% of bladder cancer lesions.18  However, there has been conflicting evidence of whether BLC also improves recurrence and progression.7-9,19  Within an equal-access setting, this study found that the risk of bladder cancer recurrence was significantly lower in patients following BLC than WLC alone. However, there was no significant difference in recurrence-free rate, progression, or survival in patients following BLC. This finding is important because it provides evidence that BLC is not superior than WLC in lowering progression or improving overall survival. Though decreased recurrence may lead to fewer follow-up treatments (e.g. TURBT), the question then becomes whether the cost of fewer but more expensive BLC is less than more frequent but less expensive WLC. Several studies report promising cost-savings with BLC, though with a few caveats. In a cost-consequence analysis of BLC, researchers found that BLC would be more cost-effective than WLC if BLC eventually improves progression rates.20  As well, in a U.S. study of new NMIBC cases, Garfield et al. estimated a cost saving using BLC of $4660 per patient over five years compared to patients initially receiving WLC; though, the generalizability may be limited as the probabilities used were primarily from the best-case scenario from prior analyses. 21  Though there is a potential of cost-savings with BLC, such a savings would not be achieved solely through decreased resource utilization due to reduced recurrence.

Second, they found decreased recurrence and longer time to recurrence following BLC. Previous research comparing WLC vs. BLC recurrence has been controversial.22  A recent Cochrane review by Maisch et al. found that BLC may reduce the risk of disease recurrence compared to white light by 34% in their aggregate analysis of 2,994 patients across 15 RCTs (HR, 0.66; 95% CI, 0.54-0.81).22  Our findings suggest in an equal access setting, BLC may not only decrease rates of recurrence but have a longer time interval to recurrence. This may have a substantial downstream impact on further diagnostic and therapeutic options for these patients aside from improved outcomes.

Third, they described BLC use and outcomes by race in an equal access setting. Racial disparities in bladder cancer care have been previously described which have been largely attributed to socioeconomic status and access to care.12,23  Blacks continually have worse bladder-cancer specific survival than all other racial/ethnic groups.23  However, there remains a lack of data examining BLC outcomes by race. Given that BLC has shown to reduce progression, recurrence, and improve overall survival, they aimed to study a more homogenous population of patients with NMIBC and describe their outcomes following BLC according to race. 24  Within the largest equal-access health care system in the United States, they found no significant difference in recurrence, progression, or survival following BLC between Black and White patients with NMIBC. Though there is robust research that show that Black patients have higher grade disease and worse disease-specific survival, there is a lack of data examining outcomes after BLC by race.25,26  They found no significant difference in recurrence, progression, or survival following BLC by race. Barocas et al. analyzed the National Cancer Database and found that appropriate treatments and improved access to care reduced the risk of mortality in bladder cancer patients by 75%, and that poorer access (income, insurance type, education, and distance from care center) most contributed to the excess risk of death.12  As reported by these authors and in our real-world study, access to care is a critical factor to mitigate racial disparities in cancer care.

The findings of the study presented at the IBCN must be interpreted within the context of the study design. First, this was a retrospective study within an equal-access health care system and the results may not be generalizable. Second, the data was both programmatically abstracted and hand- abstracted from chart reviews for several VA locations. Thus, they were unable to adjust for all potential known and unknown confounding variables and were unable to capture all the follow-up received from outside the VA system. At the same time, though, the hand re-viewing of charts may have improved the accuracy and comprehensiveness of our data compared to prior claims- only studies. Fourth, albeit larger than observed in other bladder cancer series, our cohort was limited in the number of Black patients, which limited our power for detecting modest associations.18,22,27  Nonetheless, the results suggest that outcomes following BLC in NMIBC patients did not differ significantly by race in an equal- access setting, although future larger comparative studies are needed to confirm our findings. Finally, race was self- reported in the current study. Given that race is a social construct and that our study was retrospective in nature, they thought that self- reporting was ideal for comparisons by race. This is important because race is often used as a proxy for social factors; and as our study utilized a homogenous cohort with respect to equal access to care, our findings are timely given increased focus on access to care as we cross the quality chasm. 28,29 

In the present study, the authors reported outcomes (i.e. recurrence) of patients with NMIBC receiving BLC within the VA health system. They found a significant decrease in risk of recurrence following BLC utilization compared to WLC alone. Moreover, there was no difference in any bladder cancer outcomes by race. These findings demonstrate increased support for BLC’s clinical role in reducing bladder cancer recurrence, and that equal-access to health care can achieve equitable outcomes by race.  

Presented by: Stephen B. Williams, MD, MS, FACS, Division of Urology, University of Texas Medical Branch, Galveston, TX; Department of Surgery, University of Texas Medical Branch, Galveston, TX

Written by: Stephen B. Williams, MD, MS, FACS, Division of Urology, University of Texas Medical Branch, Galveston, TX; Department of Surgery, University of Texas Medical Branch, Galveston, TX during the International Bladder Cancer Network Annual Meeting, September 28-October 1, 2022, Barcelona, Spain

  1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. Jan 2022;72(1):7-33. doi:10.3322/caac.21708
  2. Jacobs BL, Montgomery JS, Zhang Y, Skolarus TA, Weizer AZ, Hollenbeck BK. Disparities in bladder cancer. Urol Oncol. Jan-Feb 2012;30(1):81-8. doi:10.1016/j.urolonc.2011.08.011
  3. Schinkel JK, Shao S, Zahm SH, McGlynn KA, Shriver CD, Zhu K. Overall and recurrence-free survival among black and white bladder cancer patients in an equal-access health system. Cancer Epidemiol. Jun 2016;42:154-8. doi:10.1016/j.canep.2016.04.012
  4. Freudenburg E, Shan Y, Martinez A, et al. Geographic distribution of racial differences in mortality in muscle-invasive bladder cancer patients: an opportunity for improvement. Cancer Causes Control. Apr 2022;33(4):613-622. doi:10.1007/s10552-022-01553-2
  5. Freudenburg E, Bagheri I, Srinivas S, et al. Race reporting and disparities regarding clinical trials in bladder cancer: a systematic review. Cancer Causes Control. Aug 2022;33(8):1071-1081. doi:10.1007/s10552-022-01593-8
  6. Williams SB, Huo J, Kosarek CD, et al. Population-based assessment of racial/ethnic differences in utilization of radical cystectomy for patients diagnosed with bladder cancer. Cancer Causes Control. Jul 2017;28(7):755-766. doi:10.1007/s10552-017-0902-2
  7. Naselli A, Introini C, Timossi L, et al. A randomized prospective trial to assess the impact of transurethral resection in narrow band imaging modality on non-muscle-invasive bladder cancer recurrence. Eur Urol. May 2012;61(5):908-13. doi:10.1016/j.eururo.2012.01.018
  8. Geavlete B, Multescu R, Georgescu D, Jecu M, Stanescu F, Geavlete P. Treatment changes and long-term recurrence rates after hexaminolevulinate (HAL) fluorescence cystoscopy: does it really make a difference in patients with non-muscle-invasive bladder cancer (NMIBC)? BJU Int. Feb 2012;109(4):549-56. doi:10.1111/j.1464-410X.2011.10374.x
  9. Enhanced Visualization Methods for First Transurethral Resection of Bladder Tumour in Suspected Non-muscle-invasive Bladder Cancer: A Health Technology Assessment. Ont Health Technol Assess Ser. 2021;21(12):1-123.
  10. Fradet Y, Grossman HB, Gomella L, et al. 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 Urol. Jul 2007;178(1):68-73; discussion 73. doi:10.1016/j.juro.2007.03.028
  11. Rink M, Babjuk M, Catto JW, et al. 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 Urol. Oct 2013;64(4):624-38. doi:10.1016/j.eururo.2013.07.007
  12. Cole AP, Fletcher SA, Berg S, et al. Impact of tumor, treatment, and access on outcomes in bladder cancer: Can equal access overcome race-based differences in survival? Cancer. Apr 15 2019;125(8):1319-1329. doi:10.1002/cncr.31926
  13. Gidwani-Marszowski R, Faricy-Anderson K, Asch SM, Illarmo S, Ananth L, Patel MI. Potentially avoidable hospitalizations after chemotherapy: Differences across medicare and the Veterans Health Administration. Cancer. Jul 15 2020;126(14):3297-3302. doi:10.1002/cncr.32896
  14. Deswal A, Petersen NJ, Souchek J, Ashton CM, Wray NP. Impact of race on health care utilization and outcomes in veterans with congestive heart failure. J Am Coll Cardiol. Mar 3 2004;43(5):778-84. doi:10.1016/j.jacc.2003.10.033
  15. Okike K, Chan PH, Prentice HA, Navarro RA, Hinman AD, Paxton EW. Association of Race and Ethnicity with Total Hip Arthroplasty Outcomes in a Universally Insured Population. J Bone Joint Surg Am. Jul 3 2019;101(13):1160-1167. doi:10.2106/jbjs.18.01316
  16. 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. Aug 2018;36(8):361.e1-361.e6. doi:10.1016/j.urolonc.2018.04.013
  17. Jichlinski P, Leisinger HJ. Fluorescence cystoscopy in the management of bladder cancer: a help for the urologist! Urol Int. 2005;74(2):97-101. doi:10.1159/000083277
  18. 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. May 2018;199(5):1158-1165. doi:10.1016/j.juro.2017.11.096
  19. Gkritsios P, Hatzimouratidis K, Kazantzidis S, Dimitriadis G, Ioannidis E, Katsikas V. Hexaminolevulinate-guided transurethral resection of non-muscle-invasive bladder cancer does not reduce the recurrence rates after a 2-year follow-up: a prospective randomized trial. Int Urol Nephrol. May 2014;46(5):927-33. doi:10.1007/s11255-013-0603-z
  20. Klaassen Z, Li K, Kassouf W, Black PC, Dragomir A, Kulkarni GS. Contemporary cost-consequence analysis of blue light cystoscopy with hexaminolevulinate in non-muscle-invasive bladder cancer. Can Urol Assoc J. Jun 2017;11(6):173-181. doi:10.5489/cuaj.4568
  21. Garfield SS, Gavaghan MB, Armstrong SO, Jones JS. 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 Urol. Apr 2013;20(2):6682-9.
  22. Maisch P, Koziarz A, Vajgrt J, Narayan V, Kim MH, Dahm P. Blue versus white light for transurethral resection of non-muscle invasive bladder cancer. Cochrane Database Syst Rev. Dec 1 2021;12(12):Cd013776. doi:10.1002/14651858.CD013776.pub2
  23. Barocas DA, Alvarez J, Koyama T, et al. Racial variation in the quality of surgical care for bladder cancer. Cancer. Apr 1 2014;120(7):1018-25. doi:10.1002/cncr.28520
  24. Kamat AM, Cookson M, Witjes JA, Stenzl A, Grossman HB. The Impact of Blue Light Cystoscopy with Hexaminolevulinate (HAL) on Progression of Bladder Cancer - A New Analysis. Bladder Cancer. Apr 27 2016;2(2):273-278. doi:10.3233/blc-160048
  25. Yee DS, Ishill NM, Lowrance WT, Herr HW, Elkin EB. Ethnic differences in bladder cancer survival. Urology. Sep 2011;78(3):544-9. doi:10.1016/j.urology.2011.02.042
  26. Wang Y, Chang Q, Li Y. Racial differences in Urinary Bladder Cancer in the United States. Sci Rep. Aug 21 2018;8(1):12521. doi:10.1038/s41598-018-29987-2
  27. Lapini A, Minervini A, Masala A, et al. A comparison of hexaminolevulinate (Hexvix(®)) fluorescence cystoscopy and white-light cystoscopy for detection of bladder cancer: results of the HeRo observational study. Surg Endosc. Dec 2012;26(12):3634-41. doi:10.1007/s00464-012-2387-0
  28. Institute of Medicine Committee on Quality of Health Care in A. Crossing the Quality Chasm: A New Health System for the 21st Century. National Academies Press (US) Copyright 2001 by the National Academy of Sciences. All rights reserved.; 2001.
  29. Lawler C, Gu L, Howard LE, et al. The impact of the social construct of race on outcomes among bacille Calmette-Guérin-treated patients with high-risk non-muscle-invasive bladder cancer in an equal-access setting. Cancer. Nov 1 2021;127(21):3998-4005. doi:10.1002/cncr.33792


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