Post-therapy serum prostate-specific antigen level and survival in patients with androgen-independent prostate cancer

Background: With an hypothesis that post-chemotherapy changes in serum pros tate-specific antigen (PSA) levels might serve as a surrogate marker for as sessing prostate cancer outcome (i.e., survival), we studied the relationsh ip between pretherapy and post-therapy prognostic factors and survival in p atients with androgen-independent prostate cancer. Methods: A prognostic mo del for survival based on pretherapy and post-therapy parameters was develo ped from the clinical data on 254 patients with androgen-independent prosta te cancer treated with 11 different protocol therapies at Memorial Sloan-Ke ttering Cancer Center. The model was validated by use of an independent dat aset of 541 patients enrolled in two randomized phase III trials. Results: In multivariate analysis, a post-therapy decline in PSA levels of 50% achie ved in 12 weeks was a statistically significant factor associated with surv ival (two-sided P = .0012). A similar outcome was obtained with the use of an 8-week time frame. Elevated pretherapy level of serum lactate dehydrogen ase (two-sided P = .0001), lower pretherapy level of hemoglobin (P = .0001) , and younger age (two-sided P = .0430) had a statistically significant neg ative impact on outcome. Median survival times were 23, 17, and 9 months fo r low-, intermediate-, and high-risk groups of patients defined by the prog nostic model, respectively. Conclusion: This study confirms the prognostic value of a post-therapy decline in PSA of 50% or greater from baseline in r elation to survival in patients with androgen-independent prostate cancer t reated with a variety of therapies, Two consecutive determinations at 4-wee k intervals can be used as an end point for efficacy in phase II trials of therapies in this disease.