Reply to Z.S. Lalmahomed et al

Abstract

We appreciate the comments of Lalmahomed et al regarding our recent article, including the observation that low numbers of circulating tumor cells (CTCs) are observed in the peripheral circulation of patients with metastatic colon cancer, compared with the hepatic macrocirculation. Recently published data have also shown that in the setting of primary lung cancer, CTCs were positive in the peripheral blood of some patients at low numbers and in the pulmonary vein of most patients at high numbers. It is interesting to note that patients with metastatic breast and prostate cancer have higher numbers of CTCs in their peripheral blood, and liver resections in these individuals are generally unsuccessful, unlike the situation now in colon cancer. Furthermore, the presence of CTCs, even a single CTC in the peripheral blood of individuals with colorectal cancer, may indicate a poorer prognosis or those patients who are not suitable for hepatic resections. To investigate the clinical significance of low numbers of CTCs in the periphery, outcome probabilities in our series were examined (Fig 1). Although no statistically significant differences were observed, individuals with zero peripheral CTCs had numerically superior survival and progression-free survival probabilities at 12 months. This suggests that the presence of a single peripheral CTC in certain settings may have prognostic relevance. We agree that use of larger volumes of blood will lead to the discovery of more cells and thereby more material for cell characterization at the protein, RNA, and DNA levels. If the goal is to obtain more cells, then their method will work. This technique has been in practice at Munich for the SUCCESS A, B, and C trials in adjuvant breast cancer follow-up. To the best of our knowledge, in all primary cancers, investigators are routinely using more blood, 20 to 30 mLs, for analyses. Preanalytic error may, however, be introduced when layering blood over Ficoll, and a proportion of cells will inevitably be lost in doing so, although this has not been formally compared in the published abstracts thus far. Furthermore, the cutoff claimed by the manufacturer for metastatic breast cancer is no longer valid for clinical use if larger volumes of blood are used. For fairness, we are also compelled to mention that drawing three tubes and running three tubes, without concentration, is proportionately more expensive.