Blue light-enhanced versus white light resection in the treatment of non-muscle invasive bladder cancer

Review question

How does a resection (surgical removal) of bladder cancer supported with a special visualization method (blue light) compare to a standard resection with white light in people in whom a tumor of the inner bladder wall is suspected?

Background

In people suspected of having bladder cancer, suspicious tissue is cut from the inner bladder wall using a special instrument inserted through the urethra into the bladder. However, it is sometimes difficult to tell what is normal bladder versus what is cancer. In order to see the tumor better and remove it completely, a substance, or 'contrast agent,' is put into the bladder through a catheter. During surgery, a special light is used that is meant to make the cancerous area light up blue. 

Study characteristics

We only included randomized controlled trials (a type of study where participants are randomly assigned to one of two or more treatment groups) for inclusion in the review, as this type of clinical study is considered to be of the highest quality producing the most reliable results. We included people who were very likely to have had bladder cancer because if had been seen on an imaging study (like a computed tomography (CT) scan) or when looking into the bladder. We included studies of people with newly suspected tumors and those who had been treated for bladder cancer before and there was concern it had come back. 

Key results

We included 16 studies addressing our review question. Overall, blue light-enhanced resection of bladder cancer may reduce the risk of disease recurrence over time compared to white light resection (low-certainty evidence) and may reduce the risk of disease progression over time (low-certainty evidence). However, whether this effect is big enough to be meaningful to people with bladder cancer depends on whether they belong to the low, intermediate and high risk group for disease recurrence or progression.  

We also found that blue light may have little or no effect on the occurrence of serious surgical complications (low-certainty evidence) or the risk of death from bladder cancer over time (low-certainty evidence). We are very uncertain as to whether blue light TURBT reduces the incidence of unwanted side effects, as the certainty of the evidence was assessed as low. We do not know how non-serious surgical complications are affected as no data were reported for this outcome.

Quality of the evidence

The certainty of the evidence was low, meaning that future research would likely change our results.

Authors' conclusions: 

Blue light-enhanced TURBT for the treatment of non-muscle invasive bladder cancer compared to white light-based TURBT may reduce the risk of disease recurrence and disease progression over time depending on baseline risk. There may be little or no effect on serious surgical complications. The certainty of evidence for our findings was low, meaning that future studies are likely change to the reported estimates of effect. Frequent issues that led to downgrading of the certainty of the evidence were study limitations, inconsistency, and imprecision. 

Read the full abstract...
Background: 

Disease recurrence and progression remain major challenges in the treatment of non-muscle invasive bladder cancer (NMIBC). Blue light-enhanced transurethral resection of bladder cancer (TURBT) is an approach to improve staging and achieve a complete resection of NMIBC.

Objectives: 

To assess the effects of blue light-enhanced TURBT compared to white light-based TURBT in the treatment of NMIBC.

Search strategy: 

We searched several medical literature databases, including the Cochrane Library, MEDLINE, and Embase, as well as trial registers, including ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We performed a comprehensive search with no restrictions on language of publication or publication status until March 2021.

Selection criteria: 

We included randomized controlled trials using blue light versus white light TURBT. Included participants had a high level of suspicion based on imaging or ‘visible diagnosis’ for primary urothelial carcinoma of the bladder or recurrent urothelial carcinoma of the bladder upon cytoscopy. We excluded studies in which blue light was used in a surveillance setting. 

Data collection and analysis: 

Two review authors independently performed data extraction and risk of bias assessment. Our primary outcomes were time to disease recurrence, time to disease progression, and serious surgical complications. Secondary outcomes were time to death from bladder cancer, any adverse events, and non-serious complications. We rated the certainty of evidence using the GRADE approach.

Main results: 

We included 16 randomized controlled trials involving a total of 4325 participants in the review. The studies compared blue light versus white light TURBT for treatment of NMIBC. 

Primary outcomes

Blue light TURBT may reduce the risk of disease recurrence over time (hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.54 to 0.81; low-certainty evidence) depending on baseline risk. For participants with low-, intermediate-, and high-risk NMIBC, this corresponded to 48 (66 fewer to 27 fewer), 109 (152 fewer to 59 fewer), and 147 (211 fewer to 76 fewer) fewer recurrences per 1000 participants when compared to white light TURBT, respectively. 

Blue light TURBT may also reduce the risk of disease progression over time (HR 0.65, 95% CI 0.50 to 0.84; low-certainty evidence) depending on baseline risk. For participants with low-, intermediate-, and high-risk NMIBC, this corresponded to 1 (1 fewer to 0 fewer), 17 (25 fewer to 8 fewer), and 56 (81 fewer to 25 fewer) fewer progressions per 1000 participants when compared to white light TURBT, respectively.

Blue light TURBT may have little or no effect on serious surgical complications (risk ratio (RR) 0.54, 95% CI 0.14 to 2.14; low-certainty evidence). This corresponded to 10 fewer (19 fewer to 25 more) surgical complications per 1000 participants with blue light TURBT. 

Secondary outcomes

Blue light TURBT may have little or no effect on the risk of death from bladder cancer over time (HR 0.55, 95% CI 0.19 to 1.61; low-certainty evidence). This corresponded to 22 deaths per 1000 participants with white light TURBT and 10 fewer (17 fewer to 13 more) deaths per 1000 participants with blue light TURBT.  

We are very uncertain how blue light TURBT affects the outcome adverse events of any grade (RR 1.09, 95% CI 0.88 to 1.33; low-certainty evidence). 

No analysis was possible for the outcome non-serious surgical complications, as it was not reported by any of the included studies.