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JNCI Journal of the National Cancer Institute 1999 91(3):244-251; doi:10.1093/jnci/91.3.244
© 1999 by Oxford University Press
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Journal of the National Cancer Institute, Vol. 91, No. 3, 244-251, February 3, 1999
© 1999 Oxford University Press

ARTICLES

Post-therapy Serum Prostate-Specific Antigen Level and Survival in Patients With Androgen-Independent Prostate Cancer

Howard I. Scher, W. M. Kevin Kelly, Zuo-Feng Zhang, Peter Ouyang, Min Sun, Morton Schwartz, Cliff Ding, Weiping Wang, Ivan D. Horak, Alton B. Kremer

Affiliations of authors: H. I. Scher, W. M. K. Kelly, Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, and Department of Medicine, Cornell University Medical College, New York, NY; Z.-F. Zhang, M. Sun (Division of Biostatistics, Department of Epidemiology and Biostatistics), M. Schwartz (Department of Laboratory Medicine), Memorial Sloan-Kettering Cancer Center; P. Ouyang, C. Ding, W. Wang, I. D. Horak, A. B. Kremer, Janssen Pharmaceutica, Inc., Titusville, NJ.

Correspondence to: Howard I. Scher, M.D., Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021.

Present address: Z.-F. Zhang, Department of Epidemiology, School of Public Health and Johnson Comprehensive Cancer Center, University of California at Los Angeles, CA.

Present address:M. Sun, Department of Epidemiology, School of Public Health and Johnson Comprehensive Cancer Center, University of California at Los Angeles, CA.

BACKGROUND: With an hypothesis that post-chemotherapy changes in serum prostate-specific antigen (PSA) levels might serve as a surrogate marker for assessing prostate cancer outcome (i.e., survival), we studied the relationship between pretherapy and post-therapy prognostic factors and survival in patients with androgen-independent prostate cancer. METHODS: A prognostic model for survival based on pretherapy and post-therapy parameters was developed from the clinical data on 254 patients with androgen-independent prostate cancer treated with 11 different protocol therapies at Memorial Sloan-Kettering Cancer Center. The model was validated by use of an independent dataset of 541 patients enrolled in two randomized phase III trials. RESULTS: In multivariate analysis, a post-therapy decline in PSA levels of 50% achieved in 12 weeks was a statistically significant factor associated with survival (two-sided P = .0012). A similar outcome was obtained with the use of an 8-week time frame. Elevated pretherapy level of serum lactate dehydrogenase (two-sided P = .0001), lower pretherapy level of hemoglobin (P = .0001), and younger age (two-sided P = .0430) had a statistically significant negative impact on outcome. Median survival times were 23, 17, and 9 months for low-, intermediate-, and high-risk groups of patients defined by the prognostic model, respectively. CONCLUSION: This study confirms the prognostic value of a post-therapy decline in PSA of 50% or greater from baseline in relation to survival in patients with androgen-independent prostate cancer treated with a variety of therapies. Two consecutive determinations at 4-week intervals can be used as an end point for efficacy in phase II trials of therapies in this disease.


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