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European Urology
Volume 57, issue 3, pages 363-550, March 2010Letters to the Editor published online
Re: Richard J. Sylvester, Willem Oosterlinck. An Immediate Instillation after Transurethral Resection of Bladder Tumor in Non–Muscle-Invasive Bladder Cancer: Has the Evidence Changed? Eur Urol 2009;56;43–5
Sigurdur Gudjónsson a 
, Sten Holmäng b, Wiking Månsson a, Fredrik Liedberg c.
Accepted 7 November 2009, Published online 17 November 2009, pages e28 - e29
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Refers to article:
An Immediate Instillation after Transurethral Resection of Bladder Tumor in NonMuscle-Invasive Bladder Cancer: Has the Evidence Changed?
July 2009 (Vol. 56, Issue 1, pages 43 - 45)
Article Outline
Today, the European Association of Urology (EAU) guidelines recommend early instillation for all patients with non–muscle-invasive bladder cancer (NMIBC) [1]; however, no randomized prospective study exists that clearly substantiates this recommendation for intermediate and high-risk tumours.
Presently, two published studies report on the value of early instillation in addition to series of chemotherapy [2], and [3]. Both studies fail to show any clear benefit for early treatment when maintenance treatment was given. Merging two randomized studies, Bouffioux and coworkers demonstrated similar recurrence curves for early treatment and maintenance compared to delayed treatment and maintenance instillations [2]. Similarly, in the study by Hendricksen et al, no difference in time to recurrence was demonstrated when early instillation (within 48 h) was added to subsequent instillations with epirubicin [3].
One published study so far has investigated the value of early instillation in addition to bacillus Calmette-Guérin (BCG) treatment [4]. In this study (n = 161), 57% of patients in the early instillation group had no recurrence compared to 51% in the BCG-only group (p = 0.095). Although it has been pointed out that the study is underpowered, it is debatable whether such a small benefit would be clinically significant.
In a recent editorial, Sylvester and Oosterlinck [5] argue for immediate instillation in all patients with NMIBC after transurethral resection of the bladder, despite recent published data [6] suggesting that such treatment only benefits low-risk patients. It should be kept in mind that the evidence for early instillation is based on a meta-analysis that included 1476 patients, of which only 10.8% (163 patients) had recurrent tumour at inclusion and 15.7% (237 patients) had more than one tumour. In the multiple-tumour group, a separate analysis could only be conducted in 7.5% (111) of the patients, and although a trend in favour of early treatment was seen in this group of patients, it was not significant (p = 0.06). No separate analysis was published on recurrent tumours [7]. Consequently, the recent study [6] in which 104 recurrent and 117 multiple cases could be assessed adds substantially to the current knowledge on early instillation.
The inefficacy of early instillation that was found in these two subgroups is difficult to dismiss. In their editorial, Sylvester and Oosterlinck state that the effect in intermediate and high-risk tumours might be diluted due to long follow-up [5]. However, despite possible underpowering and dilution of data, the clinical efficacy in terms of numbers needed to treat (NNT) in intermediate and high-risk tumours seems to be too high in these patients to support such treatment. One should also keep in mind that 28% of patients originally included were excluded due to such factors as muscle-invasive tumours or a benign pathology report, further increasing the NNT [6]. Because 50% of recurrent tumours can be fulgurated in the office under local anaesthesia [8], our interpretation of the available literature is that such treatment cannot be recommended until there is sufficient evidence supporting a clinically significant effect.
Conflicts of interest
The authors have nothing to disclose.
References
- [1] M. Babjuk, W. Oosterlinck, R. Sylvester, et al.. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder. Eur Urol 54 (2008) (303 - 314) Abstract, Full-text, PDF, Crossref.
- [2] C. Bouffioux, K.H. Kurth, A. Bono, et al.. Intravesical adjuvant chemotherapy for superficial transitional cell bladder carcinoma: results of 2 European Organization for Research and Treatment of Cancer randomized trials with mitomycin C and doxorubicin comparing early versus delayed instillations and short-term versus long-term treatment. J Urol 153 (1995) (934 - 941)
- [3] K. Hendricksen, W.P.J. Witjes, J.G. Idema, et al.. Comparison of three schedules of intravesical epirubicin in patients with non–muscle-invasive bladder cancer. Eur Urol 53 (2008) (984 - 991) Abstract, Full-text, PDF, Crossref.
- [4] T. Cai, G. Nesi, G. Tinacci, et al.. Can early single dose instillation of epirubicin improve bacillus Calmette-Guerin efficacy in patients with non-muscle-invasive bladder cancer? Results from a prospective randomized, double-blind controlled study. J Urol 180 (2008) (110 - 115) Crossref.
- [5] R.J. Sylvester, W. Oosterlinck. An immediate instillation after transurethral resection of bladder tumor in non–muscle-invasive bladder cancer: has the evidence changed?. Eur Urol 56 (2009) (43 - 45) Abstract, Full-text, PDF, Crossref.
- [6] S. Gudjónsson, L. Adell, F. Merdasa, et al.. Should all patients with non–muscle-invasive bladder cancer receive early intravesical chemotherapy after transurethral resection? The results of a prospective randomised multicentre study. Eur Urol 55 (2009) (773 - 780)
- [7] R.J. Sylvester, W. Oosterlinck, A.P.M. van der Meijden. A single immediate postoperative instillation of chemotherapy decreases the risk of recurrence in patients with stage Ta T1 bladder cancer: a meta-analysis of published results of randomized clinical trials. J Urol 171 (2004) (2186 - 2190) Crossref.
- [8] I. Berrum-Svennung, T. Granfors, S. Jahnson, et al.. A single instillation of epirubicin after transurethral resection of bladder tumours prevents only small recurrences. J Urol 179 (2008) (101 - 106) Crossref.
Footnotes
a Malmö/Lund University Hospital, Malmö, Sweden
b Sahlgrenska University Hospital, Gothenburg, Sweden
c Växjö County Hospital, Växjö, Sweden
Corresponding author. University Hospital in Lund, Urology, Getingevägen 4, Lund, 22185 Sweden.
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