Quantity of Research Available
A total of 223 citations were identified in the literature search. Following
screening of titles and abstracts, 211 citations were excluded and 12 potentially
relevant reports from the electronic search were retrieved for full-text review. No
potentially relevant publications were retrieved from the grey literature search. Of
these potentially relevant articles, 10 publications were excluded for various
reasons, while 2 publications met the inclusion criteria and were included in this
report. Appendix 1 describes the PRISMA
flowchart of the study selection.
Additional references of potential interest are provided in Appendix 5.
Summary of Study Characteristics
The characteristics of the SRs and MAs9,10 are
briefly described below and detailed in Appendix 2.
Country of Origin
The studies were conducted by authors from the USA9 and Germany and Malaysia.10 They were all
published in 2016.
Search Methods and Results of Study Selection
Searches were conducted in multiple databases (January 1990 to October
2014)9 or
from a single database (between 2000 and 2016)10 with restriction to English language
only.9,10 One SR9 selected only RCTs,
while the other SR10
included RCTs and observational studies.
Patient Population
Most of the included studies in both SRs9,10 had mixed populations including those with new
diagnoses of bladder cancer, those with high risk bladder cancer, and those of
mixed conditions who had initial or recurrent bladder cancer. The mean age of
patients was reported in one SR and ranged from 60 to 74 years. Patients were
predominantly male.9
Interventions and Comparators
Both SRs included studies comparing fluorescent light cystoscopy with white light
cystoscopy.9,10 One SR9 included studies that
used 5-ALA or HAL, while the other SR10 included studies that used only HAL as
the photosensitizing agent.
Outcomes
The clinical outcomes included recurrence,9 progression,9,10 mortality,9 and harms.9
Follow-up Period
Follow-up period of the included studies ranged from four weeks to 60 months in
one SR9 and from one
to 55 months in the other SR.10 Follow-up was reserved for NMIBC patients of stage Ta,
T1 or CIS on initial cystoscopy.9
Data Analysis and Synthesis
Data were analyzed was a meta-analysis approach and the statistical heterogeneity
was described using the p value for the Q test and the
I2 test.9,10 In one SR,9 the recurrence was stratified according to
the duration of follow-up as short-term (<3 months), intermediate-term (3
months to <1 year) or long-term (≥1 year). Publication bias was
investigated using funnel plots.9,10
Study Appraisal
The Cochrane risk of bias tool was used by two SRs9,10 to assess the methodological quality of included
studies, and the strength of evidence for each body of evidence in one
SR9 was
assessed based on study quality, precision, consistency and directness.
Summary of Critical Appraisal
The summary of the quality assessment for the SRs are presented below and in Appendix 3.
One SR9 was of high
quality as most of the criteria were fulfilled, including an explicit research
question, a comprehensive literature search, at least two people involved in the
study selection and data extraction, a description of the relevant characteristics
of the included studies, a quality assessment of included studies, appropriate
methods of meta-analysis, appropriate assessment of the likelihood of publication
bias, and a declaration of potential conflicts of interest. Potential publication
bias was detected in both systematic reviews.9,10 The other SR10 was of moderate quality as some of the criteria were not
fulfilled or not clearly described such as a comprehensive literature search,
multiple people involved in study selection, relevant characteristics of the
included studies and appropriate methods of combining the individual study findings.
The SR10 was, however,
explicit in terms of clearly defined research question, two people involving in data
extraction, quality assessment of included studies, assessment of publication bias
and declaration of conflict of interest. Neither SR provided a list of excluded
studies.9,10
Summary of Findings
What is the clinical utility of blue light cystoscopy in patients with
suspected NMIBC undergoing TURBT?
Meta-analysis was conducted for clinical outcomes including recurrence,9 progression,9,10 and mortality.9 Harms were assessed by
detection of local adverse events.9
Appendix 4 presents main findings of
the included SRs.
Recurrence
For the detection and resection of NMIBC with TURBT, fluorescent cystoscopy
was associated with a statistically significantly reduced risk of bladder
cancer recurrence compared with white light cystoscopy at short-term
(evidence from 10 RCTs) and long-term follow-up (evidence from 12
RCTs).9
Stratifying analysis by photosensitizer showed that the effects were
statistically significant in trials using HAL, but not in trials using
5-ALA. However, the point estimates were similar and there were no
statistically significant interactions based on photosensitizer
(p for interaction = 0.97 for short-term or 0.41 for
long-term).9 Statistical heterogeneity remained in both
subgroups.9 The strength of evidence was low due to risk of
performance or publication bias.9
Progression
A pooled analysis of all trials using 5-ALA or HAL showed no difference
between fluorescent cystoscopy compared with white light cystoscopy in the
risk of progression to muscle invasive bladder cancer.9 Subgroup analysis
showed that the risk of progression was statistically significantly lower in
trials using HAL,9 but not in trials using 5-ALA.9 However, subgroup
effect was not statistically significant (p for interaction
= 0.18).9 The
strength of the evidence was moderate.9 The other SR also found that
HAL-guided TURBT was associated with statistically significant reduction in
the risk of progression compared to white light guided TURBT.10
Mortality
There was no difference in mortality between fluorescent cystoscopy and white
light cystoscopy in trials using 5-ALA or HAL.9 The strength of the evidence was low
due to imprecision and sparse data.
Harms
There was no difference between fluorescent cystoscopy and white light
cystoscopy for local adverse events such as hematuria, dysuria, urinary
frequency or urgency and bladder spasms occurred after cystoscopy.9 Data on harms were
sparse.
Limitations
One SR9 reported that
there were substantial statistical heterogeneities in some pooled analyses of
recurrence, despite the stratification of the effects by follow-up intervals. The
effects at short-term and long-term recurrence were inconsistent across trials. The
same SR also found that, in three trials, when methods were used to reduce
performance bias, fluorescent cystoscopy using HAL was not associated with
decreasing long-term recurrence.9 Funnel plots for trials investigating short-term
recurrence9 or
progression10
suggested that there was potential publication bias. The strength of the evidence
was therefore low as there was a risk of performance or publication bias. In
addition, there was insufficient evidence to understand the benefit of fluorescent
cystoscopy in patients with different risks of NMIBC or with different tumor
characteristics (i.e. grade, multiplicity, or primary versus recurrent). Follow-up
periods were not long enough to better understand the effects of fluorescent
cystoscopy on progression and mortality. No survival data could be identified.
