Changes in relative conditional survival (RCS) in de novometastatic urothelial carcinoma (mUC): A Surveillance, Epidemiology, and End Results (SEER) database analysis.

Abstract

314 Background: Currently, no agents are FDA approved for second-line treatment of mUC. Still, many patients receive second-line treatment, with data from phase II studies used as justification for payors. While this practice may not prolong disease-specific survival (DSS) for all mUC patients, assessing RCS may better account for benefit from 2nd line treatment. Methods: The SEER database was queried to compare DSS and 1-year RCS rates in de novo mUC patients diagnosed from 1994-2000 (T1) to those diagnosed from 2001-2009 (T2). The cut-off at 2000 was chosen to account for treatment variations stemming from phase II second-line trials published subequent to this date. DSS rates for T1 and T2 were modeled using Kaplan-Meier methods and compared using the log-rank test. 1-year RCS was computed annually from diagnosis through 5-years post diagnosis. The results were age standardized and compared across time periods using the z-test statistic, with 95% confidence intervals calculated using the log(log()) transformation. Multivariate Cox proportional hazard models were used to assess independent prognostic factors of DSS. Results: A total of 4,465 mUC patients were included, 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. Median DSS was 6 months for both T1 and T2 groups (P=NS). 1-year RCS rates at 1, 2, and 3 years post diagnosis, were 46%, 71%, and 76% for T1 patients compared to 39%, 68% and 78% for T2 patients (P=NS for each comparison). On MVA, older age (>65) and undifferentiated histology were independently associated with shorter DSS, while use of radiation and surgery were associated with longer DSS. Time period of diagnosis (T1 vs T2), however, had no impact on DSS. Conclusions: Multiple published phase II studies emerging over the past decade have been used to justify use of post second-line therapies for mUC to payors. In contrast to DSS, our assessment of RCS should better account for the impact of these therapies. The lack of improvement in RCS calls into question the impact post first-line therapies have on the natural history of mUC.