Circulating Tumor Cells and Sample Size: The More, the Better

TO THEEDITOR: With interest we read the article by Jiao et al, 1 who studied the presence of circulating tumor cells (CTCs) in blood of patients with colorectal liver metastases (CRLM) by automated immunomagnetic enrichment and image cytometry using the CellSearch system (Veridex, Raritan, NJ). They showed CTCs to be present in the hepatic macrocirculation in significantly higher numbersthanintheperipheralcirculation(median,187[range,0to500]v median 1 [range 0 to 6]). Despite the number of evaluated patients in this study being small, the low number of detected CTCs in the peripheral circulation may suggest that CTC enumeration and characterization plays no role in this specific patient population. Enumeration and in particular characterization of CTC holds great promise for patient management and research purposes. 2 Of severalassaysenablingCTCdetection(reviewedbyMostertetal 3 ),the CellSearch system has been approved by the US Food and Drug Administration for use in metastatic breast, prostate, and colorectal cancer.Accordingtothemanufacturer’sinstructions,CTCenumeration should be performed in 7.5 mL blood. In the first study of 196 patientswithmetastaticcolorectalcancerwhoseCTCsweremeasured with the CellSearch system. At least 2 CTCs per 7.5 mL blood were detected in 30% of patients, whereas only 17% had 5 CTCs per 7.5 mL blood. 4 In a subsequent publication by Cohen et al 5 investigating the prognostic role of CTCs in advanced colorectal cancer, patients with a CTC count above a threshold of 3 CTCs per 7.5 mL blood had a worse outcome after systemic therapy compared with patients with lower CTC counts. The 430 patients in this study received first-, second-, or third-line chemotherapy, of whom 26% had a CTC count3 CTC threshold, whereas 48% of the patients had1 CTC per 7.5 mL blood. In a third study of 451 patients with metastatic colorectal cancer, at least 3 CTCs per 7.5 mL blood were detected in 29% of the patients. 6 From these studies we can conclude that the number of detectable CTCs in patients with advanced colorectal cancer using the CellSearch System is low to even below detection limit, which is in contrast to other tumor types. In metastatic breast and prostate cancer, the percentage of patients with a CTC count of 5 CTCs per 7.5 mL was 66% and 49%, respectively. 7,8 Not surprisingly and in line with thefindings of Jiao et al, 1 in nonmetastastic colorectal cancer, the number of patients with detectable CTCs is even lower thaninadvanceddisease.Onestudyrevealed2CTCs/7.5mLintwo