Photodynamic diagnosis of non-muscle-invasive bladder cancer with hexaminolevulinate cystoscopy: a meta-analysis of detection and recurrence based on raw data

Eur Urol. 2013 Nov;64(5):846-54. doi: 10.1016/j.eururo.2013.03.059. Epub 2013 Apr 8.

Abstract

Background: Studies on hexaminolevulinate (HAL) cystoscopy report improved detection of bladder tumours. However, recent meta-analyses report conflicting effects on recurrence.

Objective: To assess available clinical data for blue light (BL) HAL cystoscopy on the detection of Ta/T1 and carcinoma in situ (CIS) tumours, and on tumour recurrence.

Design, setting, and participants: This meta-analysis reviewed raw data from prospective studies on 1345 patients with known or suspected non-muscle-invasive bladder cancer (NMIBC).

Intervention: A single application of HAL cystoscopy was used as an adjunct to white light (WL) cystoscopy.

Outcome measurements and statistical analysis: We studied the detection of NMIBC (intention to treat [ITT]: n=831; six studies) and recurrence (per protocol: n=634; three studies) up to 1 yr. DerSimonian and Laird's random-effects model was used to obtain pooled relative risks (RRs) and associated 95% confidence intervals (CIs) for outcomes for detection.

Results and limitations: BL cystoscopy detected significantly more Ta tumours (14.7%; p<0.001; odds ratio [OR]: 4.898; 95% CI, 1.937-12.390) and CIS lesions (40.8%; p<0.001; OR: 12.372; 95% CI, 6.343-24.133) than WL. There were 24.9% patients with at least one additional Ta/T1 tumour seen with BL (p<0.001), significant also in patients with primary (20.7%; p<0.001) and recurrent cancer (27.7%; p<0.001), and in patients at high risk (27.0%; p<0.001) and intermediate risk (35.7%; p=0.004). In 26.7% of patients, CIS was detected only by BL (p<0.001) and was also significant in patients with primary (28.0%; p<0.001) and recurrent cancer (25.0%; p<0.001). Recurrence rates up to 12 mo were significantly lower overall with BL, 34.5% versus 45.4% (p=0.006; RR: 0.761 [0.627-0.924]), and lower in patients with T1 or CIS (p=0.052; RR: 0.696 [0.482-1.003]), Ta (p=0.040; RR: 0.804 [0.653-0.991]), and in high-risk (p=0.050) and low-risk (p=0.029) subgroups. Some subgroups had too few patients to allow statistically meaningful analysis. Heterogeneity was minimised by the statistical analysis method used.

Conclusions: This meta-analysis confirms that HAL BL cystoscopy significantly improves the detection of bladder tumours leading to a reduction of recurrence at 9-12 mo. The benefit is independent of the level of risk and is evident in patients with Ta, T1, CIS, primary, and recurrent cancer.

Keywords: Bladder cancer; HAL blue light cystoscopy; Hexaminolevulinate.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Aminolevulinic Acid / analogs & derivatives*
  • Carcinoma in Situ / mortality
  • Carcinoma in Situ / pathology*
  • Carcinoma in Situ / therapy
  • Cystoscopy / methods*
  • Humans
  • Kaplan-Meier Estimate
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Predictive Value of Tests
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Urinary Bladder / pathology*
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology*
  • Urinary Bladder Neoplasms / therapy

Substances

  • Aminolevulinic Acid
  • 5-aminolevulinic acid hexyl ester