UCLA

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 sought to determine if a large panel of urinary cytokines measured at different time points can predict response to treatment in patients with NMIBC.

Methods and Material: Serial urine samples were collected from 50 patients with intermediate or high-risk NMIBC enrolled in a prospective, phase II randomized study evaluating intravesical BCG +/- intradermal HS-410 therapy. Urines were collected at baseline, week-7, week-13, week-28 and at end of treatment. Using a multiplex immunoassay, 105 cytokines were analyzed. To predict outcome of time to event (either recurrence or progression), univariate and multivariable Cox analyses were performed.

Results: 15 patients (30%) developed recurrence and 4 patients (8%) progressed during the follow-up. Among clinicopathologic variables, only smoking status, ever-smoker vs. non-smoker status, was associated with an improved response rate (HR 0.38, 95% CI 0.14 - 0.99, p=0.0483). In the most relevant multivariable model, the percent change (for 100 units) of IL-18 binding protein-a (HR 1.995, 95% CI 1.157-3.438, p=0.01), IL-23 (HR 1.116, 95% CI 1.012-1.23, p=0.03), IL-8 (HR 0.273, 95% CI 0.069-1.082, p=0.06), and interferon gamma-induced protein-10 (HR 0.955, 0.914-0.997, p=0.04) at week-13 from baseline best predicted time to event.

Conclusion: In a time-dependent manner, urinary cytokines provided additional value to clinicopathologic features to predict response to immune modulating agents in patients with intermediate and high risk NMIBC. Further studies are needed to validate these findings.