Correlation of disease-free survival at 2 to 3 years and 5-year overall survival in patients with muscle-invasive bladder cancer undergoing radical cystectomy.

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4576 Background: The conventional primary end point in trials of perioperative systemic therapy for muscle-invasive bladder is 5-year overall survival (OS). Disease-free survival (DFS) at 2-3 years may be an intermediate end point that correlates with 5-year OS. Methods: A multicenter (10 sites) American-European database of patients with bladder cancer that underwent radical cystectomy (RC) with negative margins from October 1971 to April 2008 was analyzed. The median follow-up was 72 months and eligible patients had muscle-invasive pathological (p)T2-T4aN0 or node-positive disease. Of a total of 2724 patients, 844 had received adjuvant chemotherapy; 997 had pT2 and 1727 patients had ≥pT3 (including node positive) disease. Recurrence and survival were analyzed to investigate the individual levels of association between DFS at 2 years (DFS2) or 3 years (DFS3) with OS at 5 years (OS5) using Cox proportional hazards modeling. The kappa statistic was calculated to determine agreement above that expected by chance. Results: The overall DFS2/DFS3 was 0.63/0.57; for pT2= 0.77/0.72 and for ≥pT3=0.54/0.48. Of all recurrences, 71.2% occurred in 2 years, and 83.4% in 3 years. The 5-year OS was 0.47; for pT2= 0.61 and for ≥pT3=0.39. The overall agreement between DFS2 and OS5 was 79%, and between DFS3 and OS5 was 81%. Agreements were similar when analyzed by stage (pT2= 82%, ≥pT3= 80%) in patients that either received (81%) or did not receive (78%) adjuvant chemotherapy, and for time of RC up to 1990 (80%) or after 1990 (79%). The kappa statistic was 0.57 (95% CI, 0.53, 0.60) for DFS2/OS5 and 0.61 (95% CI, 0.58, 0.64) for DFS3/OS5, indicating moderate agreement. The hazard ratio for progression as a time-dependent variable was 12.7 (95% CI, 11.60, 13.90) indicating a strong relationship between progression and survival. Conclusions: Both 2 and 3-year DFS correlate with and are potential intermediate surrogates for 5-year OS in patients with muscle-invasive bladder cancer undergoing RC with/without adjuvant chemotherapy. These data require validation and may also be applicable to neoadjuvant therapy and assist in accelerating the development of perioperative systemic therapy. No significant financial relationships to disclose.