Editing Bladder Cancer: Diagnosis and Evaluation (section)

==== Enhanced cystoscopy ====

===== Fluorescent (blue light) cystoscopy[https://www.ncbi.nlm.nih.gov/pubmed/17499283][https://www.ncbi.nlm.nih.gov/pubmed/17499291] =====

====== Rationale ======
* '''<span style="color:#ff0000">Improves detection of both small papillary tumors and CIS</span>'''

====== Mechanism of Action ======
* '''<span style="color:#ff0000">A photosensitizing agent, 5-aminolevulinic acid (ALA) or hexyl aminolevulinic acid (HAL), is instilled into the bladder and subsequently</span>''' '''<span style="color:#ff0000">metabolized to protoporphyrn IX by tumor cells,</span> emitting a red fluorescence under blue light'''

====== Efficacy ======
* Sensitivity for CIS 87% compared to 83% with white light
* '''Relatively high false-positive rate'''
* Reduces the rate of residual tumour by 20% compared to white light cystoscopy
* '''<span style="color:#ff00ff">NCT02560584</span>'''
** Population: 304 patients with a history of multiple, recurrent or high grade bladder tumors undergoing first surveillance cystoscopy
** Randomized to white light +/- blue light flexible cystoscopy
** Primary outcome: proportion of patients with histologically confirmed malignancy that was detected only by blue light and not by white light flexible cystoscopy in the surveillance setting.
** Results:
*** 103/403 patients found to have suspicious lesions on flexible cystoscopy and referred to operating room.
*** 63/103 found to have malignancy
**** 20% of recurrences seen only with blue-light flexible cystoscopy
** [https://pubmed.ncbi.nlm.nih.gov/29203268/ 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.
*'''<span style="color:#ff00ff">PHOTO'''
**Population: 538 patients with a suspected first diagnosis of NMIBC at intermediate or high risk for recurrence
**Randomized to white light cystoscopy vs. blue light cytoscopy
**Primary outcome: time to recurrence at 3 years of follow-up
**Results
***Time to recurrence: no significant difference
***No significant difference in progression
**[https://pubmed.ncbi.nlm.nih.gov/38319866/ Heer, Rakesh, et al. "A randomized trial of PHOTOdynamic surgery in non–muscle-invasive bladder cancer." ''NEJM evidence'' 1.10 (2022): EVIDoa2200092.]
* '''Prospective studies have shown that blue light cystoscopy decreases recurrence rates, despite a trend in decreasing progression rates and prolong time to progression, current data is inconclusive, and impact on oncologic outcomes other than recurrence remains unclear'''
** '''Most clinical trials testing BLC have not used single dose chemotherapy at the time of TURBT, so the impact of combining both interventions remains uncertain.'''
*HAL is approved for use both in Europe and the United States, but currently does not have Health Canada approval

====== Indications ======
* '''2021 CUA: can increase tumour detection at first TURBT and reduce recurrence risk.'''
* '''<span style="color:#ff0000">2024 AUA:</span> in a patient with NMIBC, blue light cystoscopy <span style="color:#ff0000">should be offered at the time of TURBT, if available,</span> to increase detection and decrease recurrence'''

====== Technique ======

* The photosensitizing agent is instilled into the bladder 1-4 hours before the procedure

===== Narrow band imaging (NBI) =====

*Filters white light into blue and green wavelengths.
*'''The light penetrates the superficial bladder tissues and is <span style="color:#ff0000">strongly absorbed by hemoglobin</span>, enhancing the contrast between normal urothelium and the blood vessels in the highly vascular malignant tumours.'''
*Does not require bladder instillation, unlike blue-light cystoscopy
*'''Improves tumour detection, but the prognostic impact remains unknown'''
**Herr and Donat (2008) performed white light and NBI cystoscopy in 427 consecutive patients with a history of NMIBC. Of the 103 patients with a tumor recurrence, 56% had additional tumors identified with NBI compared with use of WLC, and in 12% of patients, the recurrent tumor was found only with NBI. For WLC and NBI cystoscopy, the overall sensitivities were 87% and 100% and the overall specificities were 85% and 82%, respectively
*'''<span style="color:#ff0000">Guideline perspective on role of NBI cystoscopy:</span>'''
**'''<span style="color:#ff0000">CUA: NBI improves tumour detection, but the prognostic impact remains unknown</span>'''
**'''<span style="color:#ff0000">AUA:</span> in a patient with NMIBC, <span style="color:#ff0000">consider the use of NBI to increase detection and decrease recurrence</span>'''