A prospective study on the changes and clinical significance of pre-operative and post-operative circulating tumor cells in resectable gastric cancer

Abstract

Background: Circulating tumor cells (CTCs) have been suggested as potential prognostic indicators for multiple tumors, including gastric cancer; however, pre- and post-operative CTC changes in resectable gastric cancer and possible correlations to post-operative recurrence have not been evaluated.

Methods: Subjects (n = 93) with resectable gastric cancer were prospectively reviewed from July 2013 to December 2014 at Peking University Cancer Hospital. The proportion of CTCs were evaluated before (n = 93) and after (n = 63) radical operation using a standardized CellSearch system.

Results: CTCs ≥ 1 were measured in the pre-operative blood of 31 (33.3%) patients and in the post-operative blood of 21 patients (33.3%). Patients with relatively poor clinicopathological features had more pre- and post-operative CTCs. The 3-year disease-free survival (DFS) rate for patients with CTCs ≥ 5/7.5 ml was significantly lower than for patients with CTCs < 5/7.5 ml (40.0% vs 66.4%, p < 0.001 for pre-surgery; 25.0% vs 62.2%, p < 0.001 for post-surgery). Patients with CTCs ≥ 5/7.5 ml in post-operative blood had significantly shorter mean DFS (1.28 vs 31.6 months; p = 0.002) and overall survival (OS; 10.0 vs 34.9 months; p = 0.001) than other patients. Among the 10 patients with hematogenous recurrence, 3 had post-operative CTCs ≥ 2/7.5 ml and had early recurrence (DFS 1.1, 1.1, 1.4 months). Moreover, DFS for the seven patients was 20.2, 11.9, 20.0, 6.0, 15.5, 25.9, 30.0 months, respectively. DFS for the three patients with increased CTCs after surgery was shorter than for patients with mildly increased, stable, or decreased CTCs.

Conclusions: Pre- and post-operative CTCs are promising prognostic markers for resectable gastric cancer. Our study further suggests that increased post-operative CTCs may be correlated with hematogenous recurrence. Trial registration (ClinicalTrials.gov Identifier: NCT01848015). Registered 7 May 2013. https://ichgcp.net/clinical-trials-registry/NCT01848015.

Keywords: CellSearch; Circulating tumor cells; Hematogenous metastasis; Recurrence; Resectable gastric cancer.

Figures

Fig. 1

CTCs were significantly (p a), TNM classification (b), depth of penetration (c) and lymph-vascular invasion (d), and were obviously, though not significantly, correlated with age (e), differentiation (f), lymph node metastasis (g), and CEA level (h) in preoperative blood, *p < 0.05

Fig. 2

CTCs were significantly (p a) and were obviously, though not significantly, correlated with TNM classification (b) in postoperative blood, *p < 0.05

Fig. 3

3-year DFS was lower in patients who had more CTCs (a), the filled black columns represent the 3-year DFS of patients who had CTCs no more than the cut-off value, and the empty white columns represent 3-year DFS of patients who had CTC more than the cutoff value. Patients who have ≥ 5 CTCs/7.5 ml blood pre-operatively had shorter DFS (b, d) and OS (c, e)

Fig. 4

Among hematogenous metastases subjects, patients who had post-operative CTCs ≥ 2/7.5 ml (a) and patients who had markedly increased CTCs after surgery (b) had markedly shorter DFS