Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer.
OBJECTIVE
The development of tumor-specific markers to select targeted therapies and to assess clinical outcome remains a significant area of unmet need. We evaluated the association of baseline circulating tumor cell (CTC) number with clinical characteristics and survival in patients with castrate metastatic disease considered for different hormonal and cytotoxic therapies.


METHODS
CTC were isolated by immunomagnetic capture from 7.5-mL samples of blood from 120 patients with progressive clinical castrate metastatic disease. We estimated the probability of survival over time by the Kaplan-Meier method. The concordance probability estimate was used to gauge the discriminatory strength of the informative prognostic factors.


RESULTS
Sixty-nine (57%) patients had five or more CTC whereas 30 (25%) had two cells or less. Higher CTC numbers were observed in patients with bone metastases relative to those with soft tissue disease and in patients who had received prior cytotoxic chemotherapy relative to those who had not. CTC counts were modestly correlated to measurements of tumor burden such as prostate-specific antigen and bone scan index, reflecting the percentage of boney skeleton involved with tumor. Baseline CTC number was strongly associated with survival, without a threshold effect, which increased further when baseline prostate-specific antigen and albumin were included.


CONCLUSIONS
Baseline CTC was predictive of survival, with no threshold effect. The shedding of cells into the circulation represents an intrinsic property of the tumor, distinct from extent of disease, and provides unique information relative to prognosis.
Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Daniel C
DC
Danila
Glenn
G
Heller
Gretchen A
GA
Gignac
Rita
R
Gonzalez-Espinoza
Aseem
A
Anand
Erika
E
Tanaka
Hans
H
Lilja
Lawrence
L
Schwartz
Steven
S
Larson
Martin
M
Fleisher
Howard I
HI
Scher
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D001859:Bone Neoplasms / Q000097:blood / Q000473:pathology / Q000556:secondary; D018450:Disease Progression; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D009919:Orchiectomy; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology*; D012709:Serum Albumin; D000075462:Serum Albumin, Human; D012983:Soft Tissue Neoplasms / Q000097:blood / Q000473:pathology / Q000556:secondary
C422455:ALB protein, human; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D012709:Serum Albumin; D017430:Prostate-Specific Antigen; D000075462:Serum Albumin, Human