Clin Cancer Res.. [Epub ahead of print]
Prediction of Survival following First-Line Chemotherapy in Men with Castration-Resistant Metastatic Prostate Cancer.
Armstrong AJ, Garrett-Mayer E, de Wit R, Tannock I, Eisenberger M.
Affiliations: Duke Comprehensive Cancer Center and the Duke Prostate
Center, Department of Medicine, Division of Medical Oncology, Duke
University Medical Center, Durham, North Carolina; Department of
Biostatistics, Medical University of South Carolina, Charleston, South
Carolina; Department of Medical Oncology, Rotterdam Cancer Institute,
Erasmus University Medical Center, Rotterdam, the Netherlands;
Department of Medical Oncology, Princess Margaret Hospital and
University of Toronto, Toronto, Canada; and Sidney Kimmel Comprehensive
Cancer Center at Johns Hopkins, Baltimore, Maryland.
We sought to evaluate predictors of overall survival following
progression after systemic chemotherapy in men with metastatic
castration-resistant prostate cancer.
EXPERIMENTAL DESIGN: For our
study population, we used the TAX327 multicenter randomized phase III
trial comparing administration of docetaxel and prednisone every 3
weeks, weekly administration of docetaxel and prednisone, and
administration of mitoxantrone and prednisone every 3 weeks.
Progression was defined as the earliest of prostate-specific antigen
(PSA), tumor, or pain progression. We analyzed predictors of
postprogression survival according to both prechemotherapy and
postchemotherapy variables with adjustment for potential confounders.
RESULTS: Among 1,006 men, 640 had evaluable information on
protocol-defined progression leading to further therapy. Median
postprogression survival was 14.5 months. In the multivariable
analysis, several pretreatment factors were associated with
postprogression survival: pain, performance status, alkaline
phosphatase, number of sites of metastatic disease, liver metastases,
hemoglobin, PSA, and time since diagnosis. In addition, we found that
the number of progression factors (PSA, pain, and tumor size), the
duration of first-line chemotherapy, and whether progression occurred
during chemotherapy independently predicted postprogression survival.
We found evidence for the benefit of continuation of chemotherapy
beyond progression only for men who had isolated worsening of pain. A
nomogram was constructed and internally validated with a concordance
index of 0.70.
CONCLUSIONS: An internally validated model to predict
postchemotherapy survival was developed. Evaluation of men in the
postdocetaxel setting should consider the type of progression, duration
of therapy, and known pretreatment prognostic factors. Definitions of
progression in castration-resistant prostate cancer that include pain
should also consider composite measures of tumor or PSA progression.
External validation is planned. Clin Cancer Res; 16(1); OF1-9.