CYSTOSCOPY
HISTORY
While Huber Humphrey was vice president in 1967, he had hematuria and cystoscopy evaluation and follow up surveillance cystoscopies with some abnormalities but without conclusive findings of carcinoma. Unfortunately he died in 1978, two years after cystectomy and diagnosis of MIBC. (2)
RISKS
Urinary tract infection in 1-10%. (20,21) A large study of 1,245 patients who received prophylactic antibiotics had a 3% UTI rate (22). Although one large study of 3,108 cystoscopies without antibiotic prophylaxis in mostly high risk patients had a 1.9% UTI rate (23), althought another study found a 5.1% rate of UTI without antibiotic in an in-patient population. (24)
WHITE LIGHT CYSTOSCOPY (WLC)
A recent meta-analysis of 6 RCT showed WLC missed 24.9% of Ta and T1 tumors and 26.7% of CIS. (3) Other studies have found WLC misses 10-45% of tumors. (4)
BLUE LIGHT CYSTOSCOPY (BLC)
BLC uses 5-amninolevulinic acid (ALA) or hexaminolevulinate hydrochloride (HAL) which accumulates in neoplastic tissues and fluoresces to blue light between 375-440nm wavelength. HAL BLC was approved by FDA in 2010 for use in patients with history of NMIBC. In 2018, a system for flexible cystoscopes was introduced. The AUA and SUO recommends offering BLC with all patients with NMIBC and should be used in conjunction with WLC (1) .
DETECTION WITH BLC
A large study found a BLC sensitivity of 75% for CIS vs. 52.8% for WLC (p=0.02) (5) and a meta-analysis showed BLC detected significantly more Ta and CIS compared w/ WLC in high risks and intermediate risk patients with primary and recurrent tumors. (3) One study showed 21% of patients with malignancy were seen only with blue light flexible cystoscopy. Furthermore, 35% of patients had CIS seen only with blue light cystoscopy in the operating room cystoscopy and identified additional lesions in 46% of patients. False positive rate was 9% for both white and blue light cystoscopy. (1) Another study of 115 patients showed recurrence occured at a median of 12mo in BLC vs. 5mo in WLC (8) and a single center European study found a 27% reduction in 12mo recurrence rate vs. WLC. (9)
RECURRENCE WITH BLC
A larger German study found 16% decreased risk in recurrence in BLC treated group at 9mo and 6.2% lower recurrence at 54mo. BLC had a longer time to recurrence (16.4mo vs. 9.6mo). There was also a trend towards decreased risk of cystectomy in BLC group. (10,11) A large meta-analysis found 24% reduced risk of recurrence with BLC at 12mo. (3) Other studies support this. (12,13)
PROGRESSION WITH BLC
While BLC clearly increases detection and reduces recurrence, the data is not as strong for progression. There is limited data that suggets BLC can delay progression. Earlier studies that showed decrease in recurrence did not also show a reduced progression in BLC treated groups. (14,15) However, a meta-analysis found 10.7% of WLC progressed vs. 6.8% of BLC with a 64% increased odds of progression. (16)
BLC should be used in conjunction with WLC. One study showed BLC missed 9% of tumors seen by WLC, including 5% of T1 tumors. This study did find BLC detected 1 additional tumor compared to WLC in 29% with 1 additional T1 in 15% of patients. (7)
NARROW BAND IMAGING (NBI)
NBI excludes red spectrum of light and shows increased blood supply. BLC has been studies more extensively than NBI. A RCT showed 1yr post TURBT recurrence rates of NBI group 33% vs. 51% for WLC. (17) A recent meta-analysis of 25 studies showed NBI detected tumors in 10% more patients than WLC and detected 19% more lesions per patient. NBI also had a lower risk of recurrence (0.43 at 3mo and 0.81 at 9mo). (18)
NBI vs. BLC
Another meta-analysis of 15 RCT found NBI and BLC had statistically similar rates of recurrence risk, however to date there has been no head to head trial in the setting of resection or surveillance. (19)
While Huber Humphrey was vice president in 1967, he had hematuria and cystoscopy evaluation and follow up surveillance cystoscopies with some abnormalities but without conclusive findings of carcinoma. Unfortunately he died in 1978, two years after cystectomy and diagnosis of MIBC. (2)
RISKS
Urinary tract infection in 1-10%. (20,21) A large study of 1,245 patients who received prophylactic antibiotics had a 3% UTI rate (22). Although one large study of 3,108 cystoscopies without antibiotic prophylaxis in mostly high risk patients had a 1.9% UTI rate (23), althought another study found a 5.1% rate of UTI without antibiotic in an in-patient population. (24)
WHITE LIGHT CYSTOSCOPY (WLC)
A recent meta-analysis of 6 RCT showed WLC missed 24.9% of Ta and T1 tumors and 26.7% of CIS. (3) Other studies have found WLC misses 10-45% of tumors. (4)
BLUE LIGHT CYSTOSCOPY (BLC)
BLC uses 5-amninolevulinic acid (ALA) or hexaminolevulinate hydrochloride (HAL) which accumulates in neoplastic tissues and fluoresces to blue light between 375-440nm wavelength. HAL BLC was approved by FDA in 2010 for use in patients with history of NMIBC. In 2018, a system for flexible cystoscopes was introduced. The AUA and SUO recommends offering BLC with all patients with NMIBC and should be used in conjunction with WLC (1) .
DETECTION WITH BLC
A large study found a BLC sensitivity of 75% for CIS vs. 52.8% for WLC (p=0.02) (5) and a meta-analysis showed BLC detected significantly more Ta and CIS compared w/ WLC in high risks and intermediate risk patients with primary and recurrent tumors. (3) One study showed 21% of patients with malignancy were seen only with blue light flexible cystoscopy. Furthermore, 35% of patients had CIS seen only with blue light cystoscopy in the operating room cystoscopy and identified additional lesions in 46% of patients. False positive rate was 9% for both white and blue light cystoscopy. (1) Another study of 115 patients showed recurrence occured at a median of 12mo in BLC vs. 5mo in WLC (8) and a single center European study found a 27% reduction in 12mo recurrence rate vs. WLC. (9)
RECURRENCE WITH BLC
A larger German study found 16% decreased risk in recurrence in BLC treated group at 9mo and 6.2% lower recurrence at 54mo. BLC had a longer time to recurrence (16.4mo vs. 9.6mo). There was also a trend towards decreased risk of cystectomy in BLC group. (10,11) A large meta-analysis found 24% reduced risk of recurrence with BLC at 12mo. (3) Other studies support this. (12,13)
PROGRESSION WITH BLC
While BLC clearly increases detection and reduces recurrence, the data is not as strong for progression. There is limited data that suggets BLC can delay progression. Earlier studies that showed decrease in recurrence did not also show a reduced progression in BLC treated groups. (14,15) However, a meta-analysis found 10.7% of WLC progressed vs. 6.8% of BLC with a 64% increased odds of progression. (16)
BLC should be used in conjunction with WLC. One study showed BLC missed 9% of tumors seen by WLC, including 5% of T1 tumors. This study did find BLC detected 1 additional tumor compared to WLC in 29% with 1 additional T1 in 15% of patients. (7)
NARROW BAND IMAGING (NBI)
NBI excludes red spectrum of light and shows increased blood supply. BLC has been studies more extensively than NBI. A RCT showed 1yr post TURBT recurrence rates of NBI group 33% vs. 51% for WLC. (17) A recent meta-analysis of 25 studies showed NBI detected tumors in 10% more patients than WLC and detected 19% more lesions per patient. NBI also had a lower risk of recurrence (0.43 at 3mo and 0.81 at 9mo). (18)
NBI vs. BLC
Another meta-analysis of 15 RCT found NBI and BLC had statistically similar rates of recurrence risk, however to date there has been no head to head trial in the setting of resection or surveillance. (19)
- Daneshmand, Siamak, et al. "Efficacy and safety of blue light flexible cystoscopy with hexaminolevulinate in the surveillance of bladder cancer: a Phase III, comparative, multicenter study." The Journal of urology 199.5 (2018): 1158-1165.
- Hruban RH, van der Riet P, Erozan YS, Sidransky D. Molecular biology and the early detection of carcinoma of the bladder -- the case of Hubert H. Humphrey. N Engl J Med 1994;330:1276-1278
- Burger, Maximilian, et al. "Photodynamic diagnosis of non–muscle-invasive bladder cancer with hexaminolevulinate cystoscopy: a meta-analysis of detection and recurrence based on raw data." Europe
- Oude Elferink, Puck, and J. Alfred Witjes. "Blue-light cystoscopy in the evaluation of non-muscle-invasive bladder cancer." Therapeutic advances in urology 6.1 (2014): 25-33.
- Palou, Juan, et al. "Effectiveness of hexaminolevulinate fluorescence cystoscopy for the diagnosis of non‐muscle‐invasive bladder cancer in daily clinical practice: a Spanish multicentre observational study." BJU international 116.1 (2015): 37-43.
- AUA guidelines: Non Muscle Invasive Bladder Cancer. https://www.auanet.org/guidelines/bladder-cancer-non-muscle-invasive-(2016). Accessed 11/4/18.
- Grossman, H. Barton, et al. "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." The Journal of urology 178.1 (2007): 62-67.
- Daniltchenko, Dmitry I., et al. "Long-term benefit of 5-aminolevulinic acid fluorescence assisted transurethral resection of superficial bladder cancer: 5-year results of a prospective randomized study." The Journal of urology 174.6 (2005): 2129-2133.
- Dragoescu, O., et al. "Photodynamic diagnosis of non-muscle invasive bladder cancer using hexaminolevulinic acid." Rom J Morphol Embryol 52.1 (2011): 123-127.
- Stenzl, Arnulf, et al. "Hexaminolevulinate guided fluorescence cystoscopy reduces recurrence in patients with nonmuscle invasive bladder cancer." The Journal of urology 184.5 (2010): 1907-1914.
- Grossman, H. Barton, et al. "Long-term decrease in bladder cancer recurrence with hexaminolevulinate enabled fluorescence cystoscopy." The Journal of urology 188.1 (2012): 58-62.
- Mariappan, Paramananthan, et al. "Real-life Experience: Early Recurrence With Hexvix Photodynamic Diagnosis–assisted Transurethral Resection of Bladder Tumour vs Good-quality White Light TURBT in New Non–muscle-invasive Bladder Cancer." Urology 86.2 (2015): 327-331.
- Downs, Tracy M., et al. "Fluorescent (Blue Light) Cystoscopy Improved 3-Year Recurrence-Free Survival Rates of Recurrent Bladder Tumor Patients." Journal of the American College of Surgeons 225.4 (2017): e50-e51.
- Rink, Michael, 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." European urology 64.4 (2013): 624-638.
- Stenzl, Arnulf, et al. "Detection and clinical outcome of urinary bladder cancer with 5‐aminolevulinic acid‐induced fluorescence cystoscopy: a multicenter randomized, double‐blind, placebo‐controlled trial." Cancer 117.5 (2011): 938-947.
- Gakis, Georgios, and Omar Fahmy. "Systematic review and meta-analysis on the impact of hexaminolevulinate-versus white-light guided transurethral bladder tumor resection on progression in non-muscle invasive bladder cancer." Bladder cancer 2.3 (2016): 293-300.
- Naselli, Angelo, 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." European urology 61.5 (2012): 908-913.
- Zheng, Changjian, et al. "Narrow band imaging diagnosis of bladder cancer: systematic review and meta‐analysis." BJU international 110.11b (2012): E680-E687.
- Lee, Joo Yong, et al. "A network meta-analysis of therapeutic outcomes after new image technology-assisted transurethral resection for non-muscle invasive bladder cancer: 5-aminolaevulinic acid fluorescence vs hexylaminolevulinate fluorescence vs narrow band imaging." BMC cancer 15.1 (2015): 566.
- Alsaywid, Basim S., and Grahame H. H. Smith. “Antibiotic Prophylaxis for Transurethral Urological Surgeries: Systematic Review.” Urology Annals, vol. 5, no. 2, 2013, p. 61.
- Gregg, Justin R., et al. “Recent Antibiotic Treatment Increases the Risk of Urinary Tract Infection after Outpatient Cystoscopy.” Urology Practice, vol. 3, no. 2, 2016, pp. 90–96.
- Herr, Harry W. “The Risk of Urinary Tract Infection after Flexible Cystoscopy in Patients with Bladder Tumor Who Did Not Receive Prophylactic Antibiotics.” The Journal of Urology, vol. 193, no. 2, 2015, pp. 548–551.
- Cai, T., et al. “Adherence to European Association of Urology Guidelines on Prophylactic Antibiotics: An Important Step in Antimicrobial Stewardship.” European Urology, vol. 14, no. 2, 2015, pp. 276–283.
- Gregg, Justin R., et al. “An Evidence-Based Protocol for Antibiotic Use Prior to Cystoscopy Decreases Antibiotic Use without Impacting Post-Procedural Symptomatic Urinary Tract Infection Rates.” The Journal of Urology, vol. 199, no. 4, 2017, pp. 1004–1010.