Bladder CancerTransurethral 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☆
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.
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