Disease-Free Survival at 2 and 3 Years is a Significant Early Surrogate Marker Predicting the 5-Year Overall Survival in Patients Treated with Radical Cystectomy for Urothelial Carcinoma of the Bladder: External Evaluation and Validation in a Cohort of Korean Patients

Hyung Suk Kim, Chang Wook Jeong, Cheol Kwak, Hyeon Hoe Kim, Ja Hyeon Ku, Hyung Suk Kim, Chang Wook Jeong, Cheol Kwak, Hyeon Hoe Kim, Ja Hyeon Ku

Abstract

Purpose: We aimed to externally validate the association of 2- and 3-year disease-free survival (DFS) with 5-year overall survival (OS) in patients treated with radical cystectomy (RC) for urothelial carcinoma (UC) of the bladder.

Materials and methods: We reviewed the clinical data of 422 patients who underwent RC for UC of the bladder in our institution between 1991 and 2012. Survival curves were plotted with the Kaplan-Meier method. The Kappa statistic and Kendall tau-b test were used to assess the agreements between 2- and 3-year DFS and 5-year OS.

Results: In the entire study population, 2- and 3-year DFS and 5-year OS rates were 76.4, 71.5, and 67.4%, respectively. All Kappa and Kendall's tau-b test values for agreements between 2- and 3-year DFS and 5-year OS were more than 0.40, indicating moderate agreement for all patients and in each patient subgroup selected according to specific variables (all p-values <0.05). Kaplan-Meier analysis for DFS and Cox-proportional hazard models for landmark analysis at each time point indicated that most recurrences occurred within 3 years after surgery. The 5-year OS rates of patients who were recurrence-free at each time point gradually increased to more than 95% in an extended recurrence-free interval of 12-36 months.

Conclusion: Our external validation results support the existing finding that 2- and 3-year DFS can be a valid early surrogate end point to predict 5-year OS after RC in patients with UC of the bladder.

Keywords: disease-specific survival; overall survival; radical cystectomy; surrogate; urothelial carcinoma.

Figures

Figure 1
Figure 1
Overall survival and disease-free survival. (A) All patients. (B) Patients with pT2 or less disease. (C) Patients with pT3 or greater disease. Vertical bar represents 60 months.
Figure 2
Figure 2
Overall survival by disease status. (A) Overall survival of all patients by 2-year disease status. (B) Overall survival of patients with pT2 or less disease by 2-year disease status. (C) Overall survival of patients with pT3 or greater disease by 2-year disease status. (D) Overall survival of all patients by 3-year disease status. (E) Overall survival of patients with pT2 or less disease by 3-year disease status. (F) Overall survival of patients with pT3 or greater disease by 3-year disease status.
Figure 3
Figure 3
Hazard ratio of landmark analysis at each time point. (A) All patients. (B) Patients with pT2 or less disease. (C) Patients with pT3 or greater disease. Dashes indicate 95% confidence intervals.
Figure 4
Figure 4
Five-year survival rates of patients who achieved each outcome. (A) All patients. (B) Patients with pT2 or less disease. (C) Patients with pT3 or greater disease. The bars indicate 95% confidence interval.

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