Changes in conditional survival (CS) in de novo metastatic urothelial carcinoma (mUC): A Surveillance, Epidemiology, and End Results (SEER) database analysis.

Abstract

4548 Background: No agents have been approved by the US FDA for the 2nd-line treatment of mUC. Still, many US patients receive treatment in this setting, calling upon phase II datasets emerging over the past decade for payor justification. While the cumulative disease-specific survival (DSS) for mUC may not change on account of this practice, assessment of CS may allow greater focus on patients who receive post-1st-line therapies. Methods: The SEER database was queried to compare the DSS and CS of de novo mUC patients diagnosed from 1994-2000 (T1) and 2001-2009 (T2). The year 2000 was chosen as a cutoff due to multiple phase II datasets for 2nd-line regimens published subsequent to this date. DSS in subgroups divided by time period were summarized using the Kaplan-Meier method and compared using the log-rank test. The chi-square test was used to compare the CS of subgroups divided time period at annual intervals up to 5 years. Multivariate analysis (MVA) was performed to determine the relationship between DSS and clinicopathologic/treatment-related variables. Results: Outcomes were assessed for a total of 4,465 pts, with 1,155 diagnosed during T1 and 3,310 diagnosed during T2. Mean age of the overall cohort was 70, and the majority of patients had poorly differentiated or undifferentiated tumors. For the overall cohort, 1-year DSS for T1 and T2 were 23% and 25% (P=NS). At landmark analyses at 1 yr, 2 yrs and 3 yrs following diagnosis, 1-yr CS in groups diagnosed during T1 and T2 were 46% and 39%, 71% and 68%, and 76% and 78%, respectively (P=NS for each comparison). On MVA, time period of diagnosis (T1 vs T2) was not a significant predictor of DSS. Instead, older age (>65) and undifferentiated histology were predictive of poorer DSS, while use of radiation or surgery were associated with improved DSS. Conclusions: Multiple published phase II studies emerging over the past decade have been used to justify use of post-1st-line therapies for mUC to payors. Our assessment of CS should better account for the impact of these therapies as compared to cumulative DSS. The lack of improvement CS calls into question the impact post-1st-line therapies have had on the natural history of mUC.