Hexaminolevulinate hydrochloride in the detection of nonmuscle invasive cancer of the bladder

Abstract

Clinical trials have shown that hexaminolevulinate (HAL) fluorescence cystoscopy improves the detection of bladder tumors compared with standard white-light cystoscopy, resulting in more efficacious treatment. However, some recent meta-analyses report controversially on recurrence-free rates with this procedure. A systematic review of literature was performed from December 2014 to January 2015 using the PubMed, Embase and Cochrane databases for controlled trials on photodynamic diagnosis (PDD) with HAL. A total of 154 publications were found up to January 2015. Three of the authors separately reviewed the records to evaluate eligibility and methodological quality of clinical trials. A total of 16 publications were considered eligible for analysis. HAL-PDD-guided cystoscopy increased overall tumor detection rate (proportion difference 19%, 95% confidence interval [CI] 0.152-0.236) although the benefit was particularly significant in patients with carcinoma in situ (CIS) lesion (proportion difference 15.7%, 95% CI 0.069-0.245) and was reduced in papillary lesions (Ta proportion difference 5.9%, 95% CI 0.014-0.103 and T1 proportion difference 1.2%, 95% CI 0.033-0.057). Moreover, there were 15% of patients (95% CI 0.098-0.211) with at least one additional tumor seen with PDD. With regard to recurrence rates, the data sample was insufficient for a statistical analysis, although the evaluation of raw data showed a trend in favor of HAL-PDD. This meta-analysis confirms the increased tumor detection rate by HAL-PDD with a most pronounced benefit for CIS lesion.

Keywords: bladder cancer; hexaminolevulinate; meta-analysis; photodynamic diagnosis; tumor detection.

Figure 1.

Begg’s funnel plot for publication bias with the 95% confidence limits. Sample symmetry graphical assessment for the studies comparing the proportion of lesions detected using different lights.

Figure 2.

Forest plot for the graphical examination of the heterogeneity of the studies used to compare lesions’ detection using blue light and white light. The dashed line refers to the difference in the proportion of lesions detected using different lights.