Association of progression-free survival (PFS) at 2 or 3 years with overall survival (OS) at 5 years for locally advanced bladder cancer (BC): Evaluation of individual patient data (IPD) from seven randomized trials comparing local therapy with or without neoadjuvant chemotherapy (NC).

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4583 Background: We previously identified an association between PFS at 2 years (PFS2) and 3 years (PFS3) with OS at 5 years (OS5) in a multicenter database of patients with locally advanced BC undergoing surgery alone or with adjuvant chemotherapy. We aimed to validate the association using IPD from randomized trials comparing surgery (S) or radiotherapy (XRT) alone or with NC that were included in a meta-analysis conducted by the ABCMAC group. Methods: Kappa (κ) statistics were used to estimate agreement of PFS and OS. Values of κ>0.6 were considered ‘substantial’; κ>0.8 considered ‘almost perfect’. Individual level associations between PFS2 and PFS3 with OS5 were examined using Cox proportional-hazards regression models with all patients censored at 5 years. Results: IPD were available from 7 randomized trials (2,127 patients) that reported both PFS and OS. Overall, the number of patients who progressed or died was 1,129 (53.1%) at 2 years and 1,241 (58.3%) at 3 years. There were 1,306 deaths by 5 years (61.4%). The overall agreement (κ) between PFS2 and OS5 was 0.80 (95% CI: 0.72-0.82), and between PFS3 and OS5 was 0.81 (95% CI: 0.78-0.84) Agreements were similar when analyzed by stage (T2N0 vs. ≥T3-T4N0), with or without NC, and for S or XRT. Those who did not progress by 2 years (median survival 7.59 years, 95% CI: 7.38 – 7.85) or 3 years (median survival 7.64 years, 95% CI=7.42 – 7.91) were more likely to survive to 5 years compared with those who had progressed (HR=1.84 for both PFS2 and PFS3, p<0.0001, 95%CI: 1.50-2.26). Internal validation using the “leave-one-out” method confirmed the association of both PFS2 and PFS3 with OS5 (HRs ranged from 1.23 to 3.97). Conclusions: Analysis of IPD from the meta-analysis database supported individual level associations between both PFS2 and PFS3 and OS5 for patients with locally advanced BC undergoing local therapy with and without NC. These data validate the previously demonstrated association between PFS and OS, which could accelerate the completion of trials of perioperative systemic therapy for BC.