Prospective Comparison of the Prognostic Relevance of Circulating Tumor Cells in Blood and Disseminated Tumor Cells in Bone Marrow of a Single Patient's Cohort With Esophageal Cancer

Abstract

Objective: Aim of this prospective study was to evaluate the prognostic significance of disseminated tumor cells (DTCs) and circulating tumor cells (CTCs) in 1 cohort of patients with esophageal cancer (EC). Background: Hematogenous tumor cell dissemination is a key event in tumor progression, and clinical significance of DTCs and CTCs are controversially discussed in the literature. However, evaluation of both biomarker in 1 patient's cohort has not been described before. Methods: In this prospective, single-center study, 76 patients with preoperatively nonmetastatic staged EC were included. The CellSearch system was used to enumerate CTCs. Bone marrow was aspirated from the iliac crest and cells were enriched by Ficoll density gradient centrifugation. DTCs were immunostained with the pan-keratin antibody A45-B/B3. Results: Fifteen of 76 patients (19.7%) harbored CTCs, whereas in 13 of 76 patients (17.1%), DTCs could be detected. In only 3 patients (3.9%), CTCs and DTCs were detected simultaneously, whereas concordant results (DTC/CTC negative and DTC/CTC positive) were found in 54 patients (71.1%). Surprisingly, only patients with CTCs showed significant shorter overall and relapse-free survival (P = 0.038 and P = 0.004, respectively). Multivariate analyses revealed that only the CTC status was an independent predictor of overall and relapse-free survival (P = 0.007 and P < 0.001, respectively). Conclusions: This is the first study analyzing CTC and DTC status in 1 cohort of nonmetastatic patients with EC. In this early disease stage, only the CTC status was an independent, prognostic marker suitable and easy to use for clinical staging of patients with EC.

Lymph Node and Bone Marrow Micrometastases Define the Prognosis of Patients with pN0 Esophageal Cancer

“…On the contrary, Gray et al reported an association of BNMM with the T category but failed to show a significant impact on survival in univariate and multivariate analyses [33]. In line with the latter results, a recent study investigating 76 early stage esophageal cancers did not find an impact on overall and disease-free survival for BNMM positive patients [13].…”

“…Hence, the prognostic impact of LNMM remains uncertain. The significance of BNMM on patients' survival for esophageal cancers is also being debated [12][13][14]31,32]. Ryan et al analyzed 88 esophageal cancer patients with a follow-up of 10 years showing that BNMM had a significant influence on overall and disease-specific survival especially in patients without neoadjuvant treatment [14].…”

“…However, some patients develop tumor recurrence or metastatic disease despite the absence of detectable metastases by routine clinical staging and histopathological examinations at the time of surgery. Thus, an early metastatic relapse of patients after curative treatment in pN0 esophageal cancers suggests that disseminated tumor cells (DTC) or micrometastases might have already been present at the time of preoperative diagnosis [7][8][9][10][11][12][13]. Hence, conventional histopathological examination with eosin and hematoxylin (HE) might not detect single tumor cells or clusters in lymph nodes.…”

Prognostic Value of Circulating Tumour Cells detected with the CellSearch System in Esophageal Cancer Patients: A Systematic Review and Meta-Analysis

“…Based on the sampling time points, 5 studies (11,12,(25)(26)(27) only evaluated CTCs at baseline and two studies (23,24) evaluated CTCs both at baseline and intra-therapy. HRs for OS was provided in 8 sets of data from 7 studies (11,12,(23)(24)(25)(26)(27), and RFS in 3 sets of data from 3 studies (11,12,25), respectively.…”

“…Among the 7 studies included: 2 studies (26,27) were of low quality and the other 5 studies (11,12,(23)(24)(25) were of high quality, evaluated based on the NOS (Table 2). adequacy of follow-up of cohorts (≥90%).…”