(P-234) Molecular Epidemiology Study of Interferon Gamma (IFN-γ) Expression in Urothelial Bladder Cancer (UBC)

Background: IFN-γ and associated gene expression may predict long-term patient outcomes; however, this has not been studied in patients (pts) with UBC.

Objectives: The expression of IFN-γ transcript signature was characterized among pts with metastatic bladder cancer [MBC], muscle-invasive bladder cancer [MIBC], and non–muscle-invasive bladder cancer [NMIBC] to assess if IFN-γ status is associated with survival.

Methods: A tumor-based IFN-γ gene signature was evaluated among newly diagnosed pts with UBC and available tissue or biopsy samples at two hospital centers in New York. Pts aged ≥18 years diagnosed with UBC between 2004 and 2017 and who had detailed treatment and follow-up information were included. Pts with stage IV or progressing to stage IV comprised the MBC cohort while the MIBC cohort included pts with stages T2a, T2b, T3a, T3b, or T4a UBC. The NMIBC cohort included pts with carcinomas in situ (stage Ta, T1, or Tis) or stages 0a, 0is, and I. Descriptive analyses were conducted according to IFN-γ transcript signature status using pre-determined cutoff values based on tertiles, comparing those with signatures in the highest tertile to those in the lowest two tertiles. Kaplan–Meier analyses were performed for each survival outcome for each cohort and Cox proportional hazard models were built to adjust for possible confounding factors, including gender, age, body mass index, history of cancer, number of comorbidities, and smoking status. Treatment with Bacillus Calmette-Guérin therapy was also a covariate for the NMIBC models.

Results: A total of 234 tumor samples were analyzed for IFN-γ transcript signature (140 NMIBC, 38 MIBC, and 56 MBC with median follow-up times of 41.7, 13.0, and 12.9 months, respectively). Age, gender, history of cancer, and BMI were comparable across the cohorts. Median overall survival was only reached in the MIBC cohort for those with an IFN-γ transcript signature in the lowest 2 tertiles (15.03 months [95% CI: 8.50–50.60]), but was not reached at all in the NMIBC cohort. In both the reduced and fully adjusted multivariable Cox regression models, pts in the MIBC cohort with an IFN-γ transcript signature in the highest tertile had a decreased risk of mortality that reached statistical significance.

Conclusions: This study offers evidence that IFN-γ transcript signature in UBC may be a prognostic marker of long-term outcomes, given that IFN-γ signature status was associated with decreased risk of mortality in pts with MIBC. IFN-γ could be considered as a potential venue for novel treatments intervening in this molecular pathway. Future studies should explore the epidemiology of IFN-γ transcript signature in larger, unselected populations.