Impact of Aurora kinase A and B expression on response to neoadjuvant chemotherapy and patient outcome in muscle-invasive bladder cancer (MIBC).

Abstract

393 Background: Identification of robust biomarkers that predict likelihood of benefit from neoadjuvant chemotherapy (NAC) in patients with MIBC remains an unmet need. Previous studies have implicated tumor overexpression of aurora kinases A (AURKA) and B (AURKB) as a mechanism of chemo-resistance. Because overexpression of AURKA has also emerged as a potential biomarker for detection of high-risk urothelial carcinoma, we sought to characterize the expression of AURKA, AURKB with clinical outcomes in MIBC patients who received NAC and to test the hypothesis that tumor overexpression of AURKA and AURKB would predict for residual MIBC. Methods: 47 patients with MIBC who received NAC prior to cystectomy were retrospectively identified. Immunohistochemistry for AURKA and AURKB was performed on pre-treatment diagnostic transurethral resection of bladder tumors and matched cystectomy specimens. Logistic regression models were estimated to determine the impact of pre-NAC expression on pathologic staging at cystectomy. Receiver Operator Characteristic curves (ROC) were calculated to assess diagnostic predictive ability of AURKA and AURKB. AURKA and AURKB were assessed for association with relapse-free survival (RFS) and overall survival (OS) using Kaplan-Meier techniques and Cox proportional hazards models. Results: 22 of 47 [46.8%] patients had residual muscle-invasive (ypT2-4) urothelial carcinoma after NAC. Neither baseline tumor expression of AURKA (ROC = 0.54, p = 0.71) nor AURKB (ROC = 0.46, p = 0.98) predicted for ypT2-4 status. However, baseline expression of AURKA above the 75th percentile for this cohort, determined by the percentage of tumor cells positive, was associated with an inferior RFS, [HR = 3.79, [1.40, 10.26] p = 0.005] and OS, [HR = 5.84, [2.14, 15.98], p < 0.001]. Similar trends for worse survival outcomes were also observed for high AURKB levels. Conclusions: Although baseline tumor AURKA and AURKB expression did not predict for pathologic residual MIBC after NAC, high expression of AURKA and AURKB predicted for inferior RFS and OS. Further evaluation of AURKA and AURKB as potential biomarkers and therapeutic targets in MIBC is warranted.