Survival by T Stage for Patients with Localized Bladder Cancer: Implications for Future Screening Trials

Abstract

BACKGROUND: There is insufficient data to recommend screening for bladder cancer (BC). For future BC screening trials, it is important to understand how and if tumor (T) stage can act as a surrogate outcome marker for overall (OS) and cancer-specific (CSS) survival. OBJECTIVE: To characterize OS and CSS between primary tumor (T) stages in non-metastatic bladder cancer (BC) patients. METHODS: Non-metastatic BC patients were identified in the National Cancer Database (NCDB; 2004-2015) (n = 343,163) and National Cancer Institute Surveillance, Epidemiology, and End Results database (SEER) (n = 130,751). Cox multivariable regression compared relationships between T stage (LGTa, HGTa, Tis, LGT1, HGT1, T2-T4) and OS or CSS for all patients and sub-cohorts. RESULTS: Compared to stage LGTa as a reference, overall (SEER; NCDB) and cancer-specific (SEER) survival significantly declined with increasing T stage. Using SEER, OS ranged from HGTa (HR 1.16, CI 1.13-1.21, p < 0.001) to T4 (HR 5.70, CI 5.41-6.00, p < 0.001) with a steep inflection between HGT1 (HR 1.68, CI 1.63-1.73, p < 0.001) and T2 (HR 3.39, CI 3.30-3.49, p < 0.001), which was verified with NCDB. The association of stage and CSS was even more pronounced: HGTa (84% 10 year-CSS, HR 1.94, CI 1.81-2.08, p < 0.001), Tis (82% 10 year-CSS, HR 2.28, CI 2.09-2.47, p < 0.001), LGT1 (84% 10 year-CSS, HR 2.30, CI 2.11-2.51, p < 0.001), HGT1 (72% 10 year-CSS, HR 4.24, CI 4.01-4.47, p < 0.001), T2 (48% 10 year-CSS, HR 12.18, CI 11.57-12.82, p < 0.001), T3 (45% 10 year-CSS, HR 14.60, CI 13.63-15.64, p < 0.001), and T4 (29% 10 year-CSS, HR 22.76, CI 21.19-24.44, p < 0.001). CONCLUSIONS: Earlier T stage at diagnosis was associated with better OS largely due to differences in CSS. A clinically significant difference between Stage I and Stage II was verified herein in multiple cohorts. Therefore, earlier stage at diagnosis, specifically preventing muscle invasive BC, could potentially improve survival.