Development of Predictive Value of Urinary Cytokine Profile Induced During Intravesical Bacillus Calmette-Guérin Instillations for Bladder Cancer.
BACKGROUND
We sought to demonstrate a correlation between the response to treatment and the profile of urinary cytokine production during bacillus Calmette-Guérin (BCG) therapy.


METHODS
From December 2008 to February 2011, 23 patients were included in a prospective study. All patients received 6 instillations of BCG weekly. The mean follow-up period of the population was 16.9 ± 8.4 months. Refractory disease or recurrence was observed in 5 patients. Urine samples were collected and stored at -80°C, before and 4 hours after the first, third, and sixth BCG instillations. The cytokines (interleukin [IL]-2, IL-4, IL-6, IL-10, IL-17, interferon-gamma [IFNγ] and tumor necrosis factor-alpha) were quantified within the collected urine samples using cytometric bead array analysis. The quantitative variables were analyzed using Student's t test, and regression statistical analysis was performed.


RESULTS
Urinary cytokine production had increased strongly 4 hours after the sixth instillation but only mildly to moderately after the first and third instillations. IL-2 and IL-6 showed the most dramatic changes after the BCG instillations. Different urinary cytokine production profiles were demonstrated. A trend was observed for the BCG-refractory/recurrence group, with high baseline IL-6 levels, followed by low IL-6 levels before the instillations; low baseline IL-2 levels with only minor changes during treatment; the absence of IFNγ and IL-17 production; and a low peak of cytokine production at the end of treatment.


CONCLUSIONS
Analysis of the urinary cytokine production levels during BCG therapy reflect a specific immune response induced in each patient. Their assessment could allow a more reliable selection of patients eligible for this type of treatment and could help justify the use of maintenance BCG therapy.
Service d'Urologie, Hôpital Hôtel Dieu, Nantes, France; Institut National de la Santé et de la Recherché Médicale U892, Centre de Recherche en Cancérologie, Institute for Therapeutic Research at the University of Nantes, Nantes, France. Electronic address: jrigaud@chu-nantes.fr.
Jérôme
J
Rigaud
Institut National de la Santé et de la Recherché Médicale U892, Centre de Recherche en Cancérologie, Institute for Therapeutic Research at the University of Nantes, Nantes, France.
Alexandra
A
Leger
Institut National de la Santé et de la Recherché Médicale U892, Centre de Recherche en Cancérologie, Institute for Therapeutic Research at the University of Nantes, Nantes, France.
Marie-Claire
MC
Devilder
Service d'Urologie, Hôpital Hôtel Dieu, Nantes, France.
Olivier
O
Bouchot
Institut National de la Santé et de la Recherché Médicale U892, Centre de Recherche en Cancérologie, Institute for Therapeutic Research at the University of Nantes, Nantes, France.
Marc
M
Bonneville
Institut National de la Santé et de la Recherché Médicale U892, Centre de Recherche en Cancérologie, Institute for Therapeutic Research at the University of Nantes, Nantes, France.
Emmanuel
E
Scotet
D000368:Aged; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000627:therapeutic use; D016207:Cytokines / Q000652:urine*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007322:Instillation, Drug; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000652:urine
D001500:BCG Vaccine; D016207:Cytokines
BCG; IL-2; IL-6; NMIBC; Recurrence; Response