Persistent presence of postoperative circulating tumor cells is a poor prognostic factor for patients with stage I-III colorectal cancer after curative resection

Aim: To detect pre- and postoperative circulating tumor cells (CTCs) in stage I-III colorectal cancer (CRC) patients undergoing curative resection and so identify a subgroup of patients who are at high risk for relapse. Methods: Four mRNA molecular markers including human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and carcinoembryonic antigen mRNA were used to detect CTCs in 438 CRC patients underwent curative resection. Results: Out of 438 patients, 80 CRC patients were classified to preoperative (-)/postoperative (-), 221 patients were preoperative (+)/postoperative (-), while 137 patients were preoperative (+)/postoperative (+). Univariately, postoperative relapse was significantly correlated with depth of invasion (P = 0.032), lymph node metastasis (P < 0.001), vascular invasion (P = 0.001), perineural invasion (P = 0.013), and persistent presence of CTCs (P < 0.001). Using a multivariate proportional hazards regression analysis, the presence of lymph node metastasis (P = 0.012; HR, 7.652; 95% CI: 4.162-14.827), vascular invasion (P = 0.033; HR, 4.360; 95% CI: 2.793-10.847), and the persistent presence of CTCs (P < 0.001; HR, 29.486; 95% CI: 10.281-87.792) were demonstrated to be independent predictors for postoperative relapse. Combination of these three independent predictors showed that patients with any one positive predictor had a hazard ratio of sevenfold to develop postoperative relapse (P < 0.001; HR, 7.064; 95% CI: 4.354-11.464). Furthermore, the persistent presence of CTCs was strongly correlated with poorer relapse-free survival rates (all P < 0.001). Conclusion: The promising results of this study suggest that persistent presence of postoperative CTCs may be a crucial prognostic factor adjuvant to conventional tumor markers in CRC patients who have undergone curative resection. Identification of these high-risk patients of persistent CTCs positivity is important and thus could help to define patients for adjuvant therapy with this tumor entity.