Circulating tumor cells detected in follow-up predict survival outcomes in tri-modality management of advanced non-metastatic esophageal cancer: a secondary analysis of the QUINTETT randomized trial.

ABSTRACT

BACKGROUND: Our aim was to establish if presence of circulating tumor cells (CTCs) predicted worse outcome in patients with non-metastatic esophageal cancer undergoing tri-modality therapy. METHODS: We prospectively collected CTC data from patients with operable non-metastatic esophageal cancer from April 2009 to November 2016 enrolled in our QUINTETT esophageal cancer randomized trial (NCT00907543). Patients were randomized to receive either neoadjuvant cisplatin and 5-fluorouracil (5-FU) plus radiotherapy followed by surgical resection (Neoadjuvant) or adjuvant cisplatin, 5-FU, and epirubicin chemotherapy with concurrent extended volume radiotherapy following surgical resection (Adjuvant). CTCs were identified with the CellSearch® system before the initiation of any treatment (surgery or chemoradiotherapy) as well as at 6-, 12-, and 24-months post-treatment. The threshold for CTC positivity was one and the findings were correlated with patient prognosis. RESULTS: CTC data were available for 74 of 96 patients and identified in 27 patients (36.5%) at a median follow-up of 13.1months (interquartile range6.8-24.1 months). Detection of CTCs at any follow-up visit was significantly predictive of worse disease-free survival (DFS;hazard ratio [HR] 2.44; 95% confidence interval [CI] 1.41-4.24; p=0.002), regional control (HR 6.18; 95% CI 1.18-32.35; p=0.031), distant control (HR 2.93; 95% CI 1.52-5.65;p=0.001) and overall survival (OS;HR 2.02; 95% CI 1.16-3.51; p=0.013). After adjusting for receiving neoadjuvant vs. adjuvant chemoradiotherapy, the presence of CTCs at any follow-up visit remained significantly predictive of worse OS ([HR]2.02;95% [Cl]1.16-3.51; p=0.013) and DFS (HR 2.49;95% Cl 1.43-4.33; p=0.001). Similarly, any observed increase in CTCs was significantly predictive of worse OS (HR 3.14; 95% CI 1.56-6.34; p=0.001) and DFS (HR 3.34; 95% CI 1.67-6.69; p<0.001). CONCLUSION: The presence of CTCs in patients during follow-up after tri-modality therapy was associated with significantly poorer DFS and OS regardless of timing of chemoradiotherapy.