Background: In men with mCRPC receiving chemotherapy, measurable disease response by World Health Organization criteria has been demonstrated to be prognostic for overall survival (OS). We aimed to explore the association of changes in measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) with OS. Methods: Data from the control arm (n=612) of the phase III VENICE trial receiving docetaxel plus prednisone combined with placebo were available. Data on baseline clinical and laboratory variables were obtained in addition to outcome measures: best RECIST 1.0 response, PSA response and OS. Cox proportional hazards regression was used to evaluate the prognostic ability of RECIST-defined changes for OS using a 90-day landmark analysis. Results: 363 of 612 patients (59.3%) had measurable lesions, of whom 296 were evaluable for landmark analysis. 28 (9.5%) had progressive disease (PD) prior to day 90, while 58 (19.6%) had unconfirmed partial response (PR), i.e. declines ≥30% of the sum of diameters of target lesions. Median OS beyond day 90 for men with PR, stable disease (SD), and PD was 28.3, 23.3, 11.4 months, respectively (P < 0.001). In a multivariable analysis adjusting for pain, PCWG-2 subtype, type of progression (PSA vs. other), Gleason Score (≤ 7 vs. > 7), PSA, derived neutrophil-lymphocyte ratio, ECOG performance status and alkaline phosphatase, the hazard ratio (HR) for OS for patients with PR was 0.64 (95% CI 0.42 – 0.99, P = 0.045) compared to those without PR, and 1.78 (95% CI 1.07 – 2.95, P = 0.026) for those with PD compared to those without PD. PD remained significant (HR = 1.85, 95% CI 1.10 – 3.12, P = 0.020) after adjusting for PSA changes, but PR (P = 0.14) did not. Conclusions: In men with mCRPC receiving first-line docetaxel-based chemotherapy PR and PD by RECIST 1.0 within 90 days were associated with longer or shorter OS, respectively. Given the more frequent detection of measurable disease with current imaging, the accrual of patients with measurable tumors in phase II trials to assess RECIST changes may provide an objective signal of efficacy of new drugs.