Measurable disease was significantly more frequent in phase III trials accruing after 2000. Because of the subjective nature of prostate-specific antigen and bone scan changes and the robust association of objective measurable disease changes with survival, Response Evaluation Criteria in Solid Tumors changes should be a major end point in phase II trials to obtain a firm signal of efficacy before launching phase III trials. Background Because of the low historical prevalence of measurable disease in metastatic castration-resistant prostate cancer (mCRPC), phase II trials have used prostate-specific antigen (PSA) and bone scan changes as primary end points. Frequent whole-body imaging and improved computed tomography technology currently identify measurable disease more frequently, warranting consideration of objective response as a major end point. Patients and Methods Data from reported phase III trials of mCRPC were analyzed. The proportion of patients with measurable disease, setting (pre-docetaxel [D], D-based, post-D), year of starting accrual, PSA, and the requirement for symptoms were collected. The χ2 test was used to evaluate the association of variables with measurable disease rate. Results Twenty phase III trials totaling 19,276 men with mCRPC were evaluable. Three trials (n = 1289) started accruing before 2000 and 17 trials (n = 17,987) accrued after 2000. The proportion of measurable disease rate for all trials was 47.5%. The measurable disease rate was significantly higher (P < .001) in trials that accrued after 2000 versus before 2000 (48.7% vs. 31.1%; P < .001), D-based (51.8%) or post-D patients (48.9%) compared with pre-D patients (38.6%) and in trials allowing symptomatic versus asymptomatic/minimally symptomatic patients (50.1% vs. 40.0%). Conclusion The proportion of men with measurable disease was significantly higher in phase III trials of mCRPC that accrued after 2000, in D-based or post-D patients and in trials that allowed symptomatic patients. Because of the association of objective measurable changes with survival, Response Evaluation Criteria in Solid Tumors changes might warrant consideration as a major end point in phase II trials to obtain a firm signal of efficacy before launching phase III trials.