Advertisement
Editorial – referring to the article published on pp. 1398–1406 of this issue| Volume 52, ISSUE 5, P1300-1302, November 01, 2007

What is the Optimal BCG Dose in Non–Muscle-Invasive Bladder Cancer?

      The paper from the Spanish CUETO group deals with a multicentre, prospective, randomised trial comparing intravesical treatment with low-dose bacillus Calmette-Guérin (BCG; 27 mg or one-third dose), very-low-dose BCG (13.5 mg or one-sixth dose), and mitomycin C (MMC; 30 mg) in intermediate-risk patients [
      • Ojea A.
      • Nogueira J.L.
      • Solsona E.
      • et al.
      A multicentre, randomised prospective trial comparing three intravesical adjuvant therapies for intermediate-risk superficial bladder cancer: low-dose bacillus Calmette-Guerin (27 mg) versus very low-dose bacillus Calmette-Guerin (13.5 mg) versus mitomycin C.
      ]. This trial is a logical continuation of their line of clinical research. In an earlier study this group compared normal-dose or full-dose BCG (81 mg) with the lower dose of 27 mg and found similar efficacy (recurrences and progression) but lower toxicity (reference 8 from the paper). Importantly, this first study left some doubt as to the efficacy of the lower dose in high-risk patients. In the current study only intermediate-risk patients were included, and the lower dose was compared to 30 mg MMC, which probably is the drug of choice in these patients in many countries, although the dose, for example, in my country is 40 mg! However, looking at the time period this trial was designed and started I can understand the choice of 30 mg MMC. The third arm is an even lower dose, namely, one sixth of the full dose, 13.5 mg BCG. This study seems sufficiently powered with 430 patients and has a sufficient follow-up period. Therefore, the outcome seems valid and important. The lowest dose of BCG has disease-free intervals between those of one-third dose of BCG and MMC, but it was less than that of one-third dose BCG (not significant). The one-third dose of BCG was significantly better than MMC, although, again, a rather low dose of MMC was used. The best results were obtained in primary tumours and with one-third dose of BCG. So, one-sixth dose of BCG is not as effective as one-third dose of BCG, and maybe even more importantly, there is no advantage with regard to toxicity, which is similar in both BCG arms but worse than with MMC. That there are no differences in progression is not surprising in the light of the low number of events (15 in total). Therefore, the authors conclude that one-third dose of BCG seems to be the minimum effective dose for these intermediate-risk patients.
      To read this article in full you will need to make a payment

      Subscribe:

      Subscribe to European Urology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Ojea A.
        • Nogueira J.L.
        • Solsona E.
        • et al.
        A multicentre, randomised prospective trial comparing three intravesical adjuvant therapies for intermediate-risk superficial bladder cancer: low-dose bacillus Calmette-Guerin (27 mg) versus very low-dose bacillus Calmette-Guerin (13.5 mg) versus mitomycin C.
        Eur Urol. 2007; 52: 1398-1406
        • Witjes J.A.
        • van der Meijden A.P.M.
        • Debruyne F.M.J.
        The use of intravesical BCG in superficial bladder tumors. An overview.
        Urol Int. 1990; 45: 129-136
        • Shintani Y.
        • Sawada Y.
        • Inagaki T.
        • Kohjimoto Y.
        • Uekado Y.
        • Shinka T.
        Intravesical instillation therapy with bacillus Calmette-Guérin for superficial bladder cancer: study of the mechanism of bacillus Calmette-Guérin immunotherapy.
        Int J Urol. 2007; 14: 140-146
        • Saint F.
        • Kurth N.
        • Maille P.
        • et al.
        Urinary IL-2 assay for monitoring intravesical bacillus Calmette-Guérin response of superficial bladder cancer during induction course and maintenance therapy.
        Int J Cancer. 2003; 107: 434-440
        • Witjes J.A.
        • van der Meijden A.P.M.
        • Witjes W.P.J.
        • Doesburg W.
        • Schaafsma H.E.
        • Debruyne F.M.J.
        A randomized prospective study comparing intravesical instillations of mitomycin-C, BCG-Tice, and BCG-RIVM in pTa-pT1 tumors and primary carcinoma in situ of the urinary bladder. Intravesical instillations in superficial bladder cancer.
        Eur J Cancer. 1993; 29A: 1672-1676
        • Thalmann G.N.
        • Birkhaeuser F.
        • Rentsch C.A.
        • Ochsner K.
        • Studer U.E.
        Bacillus Calmette-Guérin (BCG) used for intravesical instillations in the treatment of nonmuscle invasive transitional cell carcinoma (TCC) of the bladder: does the strain matter.
        Eur Urol Suppl. 2007; 6 (abstract no. 153): 61
        • Luftenegger W.
        • Ackermann D.K.
        • Futterlieb A.
        • et al.
        Intravesical versus intravesical plus intradermal bacillus Calmette-Guérin: a prospective randomized study in patients with recurrent superficial bladder tumors.
        J Urol. 1996; 155: 483-487
        • Oosterlinck W.
        • van der Meijden A.P.M.
        • Sylvester R.
        • et al.
        Guidelines on TaT1 (non-muscle invasive) bladder cancer.
        EAU Guidelines. 2007; : 1-18
        • van der Meijden A.P.
        • Brausi M.
        • Zambon V.
        • Kirkels W.
        • de Balincourt C.
        • Sylvester R.
        Intravesical instillation of epirubicin, bacillus Calmette-Guérin and bacillus Calmette-Guérin plus isoniazid for intermediate and high risk Ta, T1 papillary carcinoma of the bladder: a European Organization for Research and Treatment of Cancer Genito-Urinary Group randomized phase III trial.
        J Urol. 2001; 166: 476-481
        • Pagano F.
        • Bassi P.
        • Milani C.
        • Meneghini A.
        • Maruzzi D.
        • Garbeglio A.
        A low dose bacillus Calmette-Guérin regimen in superficial bladder cancer therapy: is it effective?.
        J Urol. 1991; 146: 32-35
        • Rivera P.
        • Orio M.
        • Hinostroza J.
        • et al.
        Our experience with 1 mg BCG vaccine instillation in T1 stage cancer of the bladder.
        Actas Urol Esp. 1999; 23: 757-762

      Linked Article