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Clinical Cancer Research 13, 6396, November 1, 2007. doi: 10.1158/1078-0432.CCR-07-1036
© 2007 American Association for Cancer Research

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Cancer Therapy: Clinical

A Contemporary Prognostic Nomogram for Men with Hormone-Refractory Metastatic Prostate Cancer: A TAX327 Study Analysis

Andrew J. Armstrong1, Elizabeth S. Garrett-Mayer2, Yi-Chun Ou Yang2, Ronald de Wit3, Ian F. Tannock4 and Mario Eisenberger2

Authors' Affiliations: 1 Duke Comprehensive Cancer Center, Durham, North Carolina; 2 Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland; 3 Department of Medical Oncology, Rotterdam Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands; and 4 Department of Medical Oncology, Princess Margaret Hospital and University of Toronto, Toronto, Ontario, Canada

Requests for reprints: Andrew J. Armstrong, Duke Comprehensive Cancer Center, 2424 Erwin Road, Hock Plaza, Suite 606, Room 6127, Durham, NC 27705. Phone: 919-668-8797; Fax: 919-668-7117; E-mail: andrew.armstrong{at}duke.edu.

Purpose: To develop a prognostic model and nomogram using baseline clinical variables to predict death among men with metastatic hormone-refractory prostate cancer (HRPC).

Experimental Design: TAX327 was a clinical trial that randomized 1,006 men with metastatic HRPC to receive every three week or weekly docetaxel or mitoxantrone, each with prednisone. We developed a multivariate Cox model and nomogram to predict survival at 1, 2, and 5 years.

Results: Ten independent prognostic factors other than treatment group were identified in multivariate analysis: (a) presence of liver metastases [hazard ratio (HR), 1.66; P = 0.019], (b) number of metastatic sites (HR, 1.63 if ≥2 sites; P = 0.001), (c) clinically significant pain (HR, 1.48; P < 0.0001), (d) Karnofsky performance status (HR, 1.39 if ≤70; P = 0.016), (e) type of progression (HR, 1.37 for measurable disease progression and 1.29 for bone scan progression; P = 0.005 and 0.01, respectively), (f) pretreatment prostate-specific antigen (PSA) doubling time (HR, 1.19 if <55 days; P = 0.066), (g) PSA (HR, 1.17 per log rise; P < 0.0001), (h) tumor grade (HR, 1.18 for high grade; P = 0.069), (i) alkaline phosphatase (HR, 1.27 per log rise; P < 0.0001), and (j) hemoglobin (HR, 1.11 per unit decline; P = 0.004). A nomogram was developed based on this multivariate model and validated internally using bootstrap methods, with a concordance index of 0.69.

Conclusions: This multivariate model identified several new independent prognostic factors in men with metastatic HRPC, including PSA doubling time, and led to the successful development of a clinically applicable nomogram. External prospective validation may support the wider use of this prognostic baseline model for men with HRPC treated with chemotherapy.




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