Elsevier

European Urology

Volume 57, Issue 2, February 2010, Pages 293-299
European Urology

Bladder Cancer
Transurethral Resection of Non–Muscle-Invasive Bladder Transitional Cell Cancers With or Without 5-Aminolevulinic Acid Under Visible and Fluorescent Light: Results of a Prospective, Randomised, Multicentre Study

https://doi.org/10.1016/j.eururo.2009.10.030Get rights and content

Abstract

Background

Fluorescent light (FL)–guided cystoscopy induced by 5-aminolevulinic acid (5-ALA) has been reported to detect more tumours compared with standard white-light (WL) cystoscopy. Most reports are from single centres with relatively few patients.

Objective

To evaluate whether 5-ALA–induced FL and WL cystoscopy at transurethral resection (TUR) is superior compared with standard procedures under WL only with respect to tumour recurrence and progression in patients with non–muscle-invasive bladder cancer.

Design, setting, and participants

This randomised, multicentre, observer- and pathologist-blinded, prospective phase 3 clinical trial enrolled 300 patients, and of those patients, 153 were randomised to FL cystoscopy and 147 were randomised to standard WL cystoscopy.

Intervention

All patients were first inspected under WL and all lesions were recorded. Patients randomised to FL underwent a second inspection. TUR was carried out in both groups.

Measurements

Control cystoscopy under WL was performed in all patients every 3 mo during the first year after randomisation and biannually thereafter.

Results and limitations

At the first TUR, the mean number of resection specimens per patient was 2.5 (FL: 2.5; WL: 2.4; p = 0.37) and the resulting mean number of resected tumours was 1.7 with FL and 1.8 with WL (p = 0.85). More patients were diagnosed with carcinoma in situ (CIS) in the WL group (13%) than in the FL group (4.2%). Within-patient comparison of FL patients only showed that FL detected more lesions than WL. Tumour lesions solely detected by FL cystoscopy that would not otherwise be detected by WL cystoscopy included 52% dysplasia, 33% CIS, 18% papillary neoplasms, 13% pT1, and 7% pTa. Outcome at 12 mo did not show any difference between groups with regard to recurrence-free and progression-free survival rates.

Conclusions

In this prospective, randomised, multi-institutional study, we found no clinical advantage of FL cystoscopy compared with WL cystoscopy and TUR.

Introduction

Approximately 70% of all patients with newly diagnosed transitional cell bladder cancer have non–muscle-invasive bladder cancer (NMIBC) [1]. Initial treatment of such lesions consists of complete transurethral resection (TUR), but residual tumours are found in up to 78% of cases [2], [3], [4], [5], [6], [7], [8]. Furthermore, the probability of recurrence at 1 yr ranges from about 15% to 70% [9]. The high incidence of recurrence is mostly due to incomplete resection of the primary tumour and failure to resect nonvisible urothelial lesions.

A second resection 2–6 wk later is often performed in stage pT1 tumours to reduce the risk of incomplete resections but still does not result in destruction of nonvisible lesions [3]. White light (WL) is considered the reference standard for visualising tumours at cystoscopy, but its sensitivity and specificity is not entirely satisfactory [10], [11].

In the past, numerous attempts have been made to develop optical markers for the detection of urothelial tumours to improve the clinical results of TUR. To date, 5-aminolevulinic acid (5-ALA)–induced fluorescent light (FL) cystoscopy has been studied most comprehensively, and long-term data are available [12], [13], [14], [15], [16].

The aim of the present study was to evaluate whether the addition of FL to WL cystoscopy would result in less recurrence and progression compared with WL only at TUR in patients with NMIBC. Only single-centre studies had been published when this study began.

Section snippets

Inclusion criteria

Patients (>19 yr of age) with suspected NMIBC (first diagnosis or recurrence) based on at least one documented cystoscopy (Table 1) were included.

Exclusion criteria

Patients were excluded if they had a World Health Organisation general health status score of >2 (Eastern Cooperative Oncology Group), porphyria or hypersensitivity to porphyrins, renal and/or hepatic impairment, malignancies other than basalioma, pregnancy (planned or existing), or simultaneous participation in other trials.

Randomisation

Randomisation was

Results

Between 2002 and 2005, 300 patients with suspected NMIBC were randomised to either TUR with WL cystoscopy (n = 147) or TUR with WL plus FL cystoscopy (n = 153; Table 1). Of the 300 patients, 21 (7%) were excluded from the full-analysis set. Reasons for exclusion were radical cystectomy based on the results of the primary TUR (4.7%) and no first cystoscopy (2.3%). No differences were seen between the two treatment groups.

Four patients (1.4%) received adjuvant instillation therapy within 3 mo prior

Discussion

This report is the first from a randomised, multicentre (five centres in Sweden), observer- and pathologist-blinded, prospective phase 3 study that shows no benefit from using FL-guided cystoscopy in patients with NMIBC. The reasons for this surprising finding are not known.

One factor may be that our study included not only patients with newly diagnosed NMIBC but also patients with recurrent tumours. In the present study, half of the patients presented with recurrent bladder tumours prior to

Conclusions

FL cystoscopy with 5-ALA did not detect more NMIBC tumours than WL cystoscopy. Comparing the 12-mo outcome, there were no differences between treatment groups with regard to recurrence-free survival or progression-free survival rates. In comparison with the group of patients receiving no treatment, the instillation of 5-ALA was safe and well tolerated.

References (27)

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