Urinary IL-2 assay for monitoring intravesical bacillus Calmette-Guérin response of superficial bladder cancer during induction course and maintenance therapy

Authors

  • Fabien Saint,

    1. Department of Urology, EMI-INSERM 03/37, Hôpital Henri Mondor, AP-HP Assistance Publique Hospitaux de Paris, Faculté de Médecine, Université Paris, Créteil, France
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  • Nathalie Kurth,

    1. Department of Urology, EMI-INSERM 03/37, Hôpital Henri Mondor, AP-HP Assistance Publique Hospitaux de Paris, Faculté de Médecine, Université Paris, Créteil, France
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  • Pascale Maille,

    1. Department of Urology, EMI-INSERM 03/37, Hôpital Henri Mondor, AP-HP Assistance Publique Hospitaux de Paris, Faculté de Médecine, Université Paris, Créteil, France
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  • Dimitri Vordos,

    1. Department of Urology, EMI-INSERM 03/37, Hôpital Henri Mondor, AP-HP Assistance Publique Hospitaux de Paris, Faculté de Médecine, Université Paris, Créteil, France
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  • Andre Hoznek,

    1. Department of Urology, EMI-INSERM 03/37, Hôpital Henri Mondor, AP-HP Assistance Publique Hospitaux de Paris, Faculté de Médecine, Université Paris, Créteil, France
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  • Pascale Soyeux,

    1. Department of Urology, EMI-INSERM 03/37, Hôpital Henri Mondor, AP-HP Assistance Publique Hospitaux de Paris, Faculté de Médecine, Université Paris, Créteil, France
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  • Jean Jacques Patard,

    1. Department of Urology, EMI-INSERM 03/37, Hôpital Henri Mondor, AP-HP Assistance Publique Hospitaux de Paris, Faculté de Médecine, Université Paris, Créteil, France
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  • Claude C. Abbou,

    1. Department of Urology, EMI-INSERM 03/37, Hôpital Henri Mondor, AP-HP Assistance Publique Hospitaux de Paris, Faculté de Médecine, Université Paris, Créteil, France
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  • Dominique K. Chopin

    Corresponding author
    1. Department of Urology, EMI-INSERM 03/37, Hôpital Henri Mondor, AP-HP Assistance Publique Hospitaux de Paris, Faculté de Médecine, Université Paris, Créteil, France
    • Service d'Urologie, Hôpital Henri Mondor, 51 Avenue du Maréchal de Lattre de Tassigny, CHRU de Créteil, 94000 Créteil Cedex, France
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    • Fax: +33-1-49-81-35-52


Abstract

We evaluated the clinical significance of Th1(IL-2)/Th2(IL-10) urinary profiles during a weekly induction course lasting 6 weeks, followed by a weekly maintenance therapy schedule for 3 weeks. Urinary IL-2 and /IL-10 were measured by ELISA in 39 patients receiving BCG for superficial bladder cancer or carcinoma in situ. Measurements were made after each instillation of 81 mg of BCG Connaught (Immucyst) during the induction course and the 3-week maintenance therapy (given at 3, 6, 12, 18, 24, 30 and 36 months). Cytokine levels were correlated with the risk of recurrence, progression, leukocyturia and adverse events. Median follow-up was 35 months (range 7–72 months). Complete responses to BCG were obtained in 30 patients (77%); the remaining 9 patients relapsed (23%), and 4 of these patients progressed (10.2%). Failure to detect urinary IL-2 during BCG induction course and the first extended induction cycle (6+3 schedule) correlated with time to recurrence (p = 0.01) and progression (p = 0.01). During the extended induction cycle, the first instillation was associated with an IL-2 cytokine profile, whereas the second and third instillations were associated with a switch to an IL-10 cytokine profile. This switch was associated with leukocyturia (p = 0.0001) and adverse events (p = 0.03). The 6+3 schedule is associated with urinary IL-2 overproduction and improved recurrence- and progression-free survival. During the BCG extended induction cycle, the favorable IL-2 urinary cytokine pattern gradually switches to an IL-10 profile, suggesting that the schedule based on 3 weekly instillations may be unsuitable for some patients and that the dose and frequency of maintenance BCG instillations may be adapted to individual urinary cytokine levels. © 2003 Wiley-Liss, Inc.

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