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Persistent Presence of Postoperative Circulating Tumor Cells is a Poor Prognostic Factor for Patients with Stage I–III Colorectal Cancer after Curative Resection

¹ Division of General Surgery, Department of Surgery, Chi Mei Foundation Medical Center, Taipei Medical University, Taipei, Taiwan
² Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
³ Department of Emergency Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
⁴ Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 100 Tzyou 1st Road, Kaohsiung 807, Taiwan
⁵ Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
⁶ Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
⁷ Faculty of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan
⁸ Department of Medical Research, Fooyin University Hospital, Kaohsiung, Taiwan

Correspondence: Address correspondence and reprint requests to: Jaw-Yuan Wang, MD, PhD; E-mail: cy614112{at}ms14.hinet.net

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.

Key Words: Circulating tumor cells • Molecular markers • Colorectal cancer • Prognosis • Postoperative surveillance