The Association Between Measures of Progression and Survival in Castrate-Metastatic Prostate Cancer

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Abstract
Purpose: To explore the association between progression-free survival and overall survival time in patients with castration-resistant prostate cancer treated with microtubule-targeted therapies. Experimental Design: We retrospectively studied patients treated in three trials evaluating a taxane or an epothilone for progressive castration-resistant prostate cancer. Study subjects were 98 patients with bone metastases; 63 of them also had soft tissue lesions. All scans were reviewed independently. Associations of radiographic progression-free survival and prostate-specific antigen (PSA) progression-free survival with survival time were measured using Kendall's τ, adjusted for right censoring. A smoothing procedure was applied to estimate Kendall's τ within each neighborhood of the follow-up process. Results: The overall associations between progression-free survival time and overall survival time were moderate: 0.4 for radiographic progression-free survival and 0.33 for PSA progression-free survival. The association between radiographic progression-free survival and overall survival was weakest early in the follow-up process, whereas the PSA association was weakest when the progression-free survival–related event (PSA progression, death, or censoring) occurred after 6 months from the start of treatment. Conclusions: Current measures of progression-free survival time for men with castration-resistant prostate cancer are not strongly concordant with survival time. Factors that attenuate the association include interval censoring and the discontinuation of therapy early in the follow-up due to imaging changes that may not reflect true failure of the treatment. For radiographic progression-free survival, the association may be increased by requiring confirmation of progression with a second scan, as is routinely done when assessing response.