Urinary cytokine profile to predict response to intravesical BCG with or without HS-410 therapy in patients with non-muscle invasive bladder cancer.

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Urinary cytokine profile to predict response to intravesical BCG with or without HS-410 therapy in patients with non-muscle invasive bladder cancer.

Cancer Epidemiol Biomarkers Prev. 2018 Dec 28;:

Authors: Salmasi A, Elashoff DA, Guo R, Upfill-Brown A, Rosser CJ, Rose JM, Giffin LC, Gonzalez LE, Chamie K

Abstract
BACKGROUND: Despite extensive research to identify biomarkers of response in patients with non-muscle-invasive bladder cancer (NMIBC), there is no biomarker to date that can serve this purpose. Herein, we report how we leveraged serial urine samples to query a panel of cytokines at varying time points in an attempt to identify predictive biomarkers of response in NMIBC.
METHODS: Serial urine samples were collected from 50 patients with intermediate- or high-risk NMIBC enrolled in a phase II study, evaluating intravesical BCG +/- intradermal HS-410 therapy. Samples were collected at baseline, week-7, week-13, week-28 and at end of treatment. 105 cytokines were analyzed in each sample. To predict outcome of time to event (recurrence or progression), univariate and multivariable Cox analyses were performed.
RESULTS: 15 patients developed recurrence and 4 patients progressed during the follow-up period. Among clinicopathologic variables, ever-smoker vs non-smoker status was associated with an improved response rate (HR 0.38, 95%CI 0.14-0.99, p=0.04). In the most clinically relevant model, the percent change (for 100 units) of IL-18 binding protein-a (HR 1.995, 95%CI 1.16-3.44, p=0.01), IL-23 (HR 1.12, 95%CI 1.01-1.23, p=0.03), IL-8 (HR 0.27, 95%CI 0.07-1.08, p=0.06), and interferon-gamma-induced-protein-10 (HR 0.95, 95%CI 0.91-0.99, p=0.04) at week-13 from baseline best predicted time to event.
CONCLUSIONS: Urinary cytokines provided additional value to clinicopathologic features to predict response to immune modulating agents in patients with NMIBC.
IMPACT: This study serves as a hypothesis generating report for future studies to evaluate the role of urine cytokines as a predictive biomarker of response to immune treatments.

PMID: 30593457 [PubMed - as supplied by publisher]

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