The Added Value of Circulating Tumor Cell Enumeration to Standard Markers in Assessing Prognosis in a Metastatic Castration-Resistant Prostate Cancer Population.
Purpose:Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease for which better prognostic models for survival are needed. We examined the added value of circulating tumor cell (CTC) enumeration relative to common prognostic laboratory measures from patients with CRPC.Methods:Utility of CTC enumeration as a baseline and postbaseline prognostic biomarker was examined using data from two prospective randomized registration-directed trials (COU-AA-301 and ELM-PC4) within statistical models used to estimate risk for survival. Discrimination and calibration were used to measure model predictive accuracy and the added value for CTC enumeration in the context of a Cox model containing albumin, lactate dehydrogenase (LDH), PSA, hemoglobin, and alkaline phosphatase (ALK). Discrimination quantifies how accurately a risk model predicts short-term versus long-term survivors. Calibration measures the closeness of actual survival time to the predicted survival time.Results:Adding CTC enumeration to a model containing albumin, LDH, PSA, hemoglobin, and ALK ("ALPHA") improved its discriminatory power. The weighted c-index for ALPHA without CTCs was 0.72 (SE, 0.02) versus 0.75 (SE, 0.02) for ALPHA + CTCs. The increase in discrimination was restricted to the lower-risk cohort. In terms of calibration, adding CTCs produced a more accurate model-based prediction of patient survival. The absolute prediction error for ALPHA was 3.95 months (SE, 0.28) versus 3.75 months (SE, 0.22) for ALPHA + CTCs.Conclusions:Addition of CTC enumeration to standard measures provides more accurate assessment of patient risk in terms of baseline and postbaseline prognosis in the mCRPC population.Clin Cancer Res; 23(8); 1967-73. ©2016 AACR.
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. hellerg@mskcc.org.
Glenn
G
Heller
Department of Cancer Medicine, Institute Gustave Roussy, Villejuif, France.|Department of Oncology, University of Paris, Paris, France.
Karim
K
Fizazi
Janssen Oncology Research & Development, Raritan, New Jersey.
Robert
R
McCormack
Janssen Research & Development, Menlo Park, California.
Arturo
A
Molina
Millennium Pharmaceuticals Inc., Cambridge, Massachusetts.
David
D
MacLean
Millennium Pharmaceuticals Inc., Cambridge, Massachusetts.
Iain J
IJ
Webb
Department of Surgery, University of Montréal, Montréal, Québec, Canada.
Fred
F
Saad
Prostate Cancer Targeted Therapy Group, The Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, London, United Kingdom.
Johann S
JS
de Bono
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.|Department of Medicine, Weill Cornell Medical College, New York, New York.
Howard I
HI
Scher
D000069501:Abiraterone Acetate / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000008:administration & dosage; D009360:Neoplastic Cells, Circulating; D011239:Prednisolone / Q000008:administration & dosage; D011379:Prognosis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D007093:Imidazoles; D009281:Naphthalenes; D011239:Prednisolone; D000069501:Abiraterone Acetate; C571806:orteronel
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