Affiliation:
1. Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
2. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA
3. Jesse Brown, VA Medical Center, Chicago, IL, USA
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.