Editing Bladder Cancer: Diagnosis and Evaluation (section)

=== Cystoscopy ===
* Non–muscle-invasive cancers can be very large because of lack of genetic alterations required for invasion. Likewise, invasive tumors can be quite small if early genetic changes occur within the tumor cell, allowing for an invasive phenotype
* T1 tumors are usually papillary and often have a narrow stalk; a nodular or sessile appearance suggests deeper invasion
* Methods to reduce pain associated with cystoscopy based on randomized trials (2):
*# Flexible cystoscope
*# “bag squeeze” technique (applying pressure to the saline bag during cystoscopy at the level of the membranous / prostatic urethra)

==== 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>'''