Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer.
OBJECTIVE
As treatment options expand for metastatic colorectal cancer (mCRC), a blood marker with a prognostic and predictive role could guide treatment. We tested the hypothesis that circulating tumor cells (CTCs) could predict clinical outcome in patients with mCRC.


METHODS
In a prospective multicenter study, CTCs were enumerated in the peripheral blood of 430 patients with mCRC at baseline and after starting first-, second-, or third-line therapy. CTCs were measured using an immunomagnetic separation technique.


RESULTS
Patients were stratified into unfavorable and favorable prognostic groups based on CTC levels of three or more or less than three CTCs/7.5 mL, respectively. Patients with unfavorable compared with favorable baseline CTCs had shorter median progression-free survival (PFS; 4.5 v 7.9 months; P = .0002) and overall survival (OS; 9.4 v 18.5 months; P < .0001). Differences persisted at 1 to 2, 3 to 5, 6 to 12, and 13 to 20 weeks after therapy. Conversion of baseline unfavorable CTCs to favorable at 3 to 5 weeks was associated with significantly longer PFS and OS compared with patients with unfavorable CTCs at both time points (PFS, 6.2 v 1.6 months; P = .02; OS, 11.0 v 3.7 months; P = .0002). Among nonprogressing patients, favorable compared with unfavorable CTCs within 1 month of imaging was associated with longer survival (18.8 v 7.1 months; P < .0001). Baseline and follow-up CTC levels remained strong predictors of PFS and OS after adjustment for clinically significant factors.


CONCLUSIONS
The number of CTCs before and during treatment is an independent predictor of PFS and OS in patients with metastatic colorectal cancer. CTCs provide prognostic information in addition to that of imaging studies.
Cohen
Steven J
SJ
Fox Chase Cancer Center, Philadelphia, PA 19111, USA. S_Cohen@fccc.edu
Punt
Cornelis J A
CJ
Iannotti
Nicholas
N
Saidman
Bruce H
BH
Sabbath
Kert D
KD
Gabrail
Nashat Y
NY
Picus
Joel
J
Morse
Michael
M
Mitchell
Edith
E
Miller
M Craig
MC
Doyle
Gerald V
GV
Tissing
Henk
H
Terstappen
Leon W M M
LW
Meropol
Neal J
NJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000473:pathology*; D003952:Diagnostic Imaging; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate