Prognostic Value of Circulating Tumor Cells and Circulating Tumor Microemboli in Locally Advanced Rectal Cancer Treated with Neoadjuvant Chemoradiotherapy

Abstract

This study aimed to evaluate the prognostic value of circulating tumor cells (CTCs) and CTC clusters, termed circulating tumor microemboli (CTM), detected in patients with locally advanced rectal cancer (LARC) undergoing standard neoadjuvant chemoradiotherapy. From September 2014 to August 2015, the clinicopathological variables, such as gender, age, tumor location, depth of invasion, lymphatic invasion, distant metastasis, TNM stage, CTCs and CTM enumeration before chemoradiotherapy, of 42 newly acquired and histopathologically confirmed LARC patients were collected from the Fudan University Shanghai Cancer Center. All patients were followed up for survival until the end of December 2019. Statistical analysis focused on the associations between CTCs counts, CTM and clinicopathological variables. Overall survival (OS) and progression-free survival (PFS) among different prognostic factors were calculated using the Kaplan–Meier method, and the differences between the survival curves were compared by using the log-rank test. Factors of prognostic significance were investigated with the multivariate Cox regression analysis. CTCs and CTM were detected in 32% (13/42) and 57% (24/42) of patients, respectively. CTC-positive rate was positively correlated with the depth of invasion, lymphatic invasion, distant metastasis, TNM stage, and serum CEA level (P<0.05 for all). However, no significant difference was found between CTC-positive and other clinicopathological variables (P>0.05 for all), such as gender, age, tumor location, and tumor de-differentiation. CTCs counts gradually increased with the advancement of depth of invasion (P = 0.002), lymphatic invasion (P = 0.004), distant metastasis (P = 0.007), TNM stage (P = 0.001), serum CEA level (P = 0.001), and decreased tumor de-differentiation (P = 0.011). Furthermore, the Kaplan–Meier survival curves showed that patients with CTC-positive had a significantly unfavorable PFS (28 vs. 46 months, P = 0.001) and OS (36 vs. 50 months, P = 0.003). The multivariate Cox regression analyses revealed that the presence of CTCs before chemoradiotherapy was an independent factor for unfavorable PFS (hazard ratio (HR) 2.682, P = 0.017, 95% confidence interval (CI) 1.193–6.029) and OS (HR 2.790, P = 0.048, 95% CI 1.010–7.705) in LARC patients. This study provided an evidence that the presence of pretreatment CTCs may be valuable for predicting survival outcome, and CTCs was associated with unfavorable survival in LARC patients treated with neoadjuvant chemoradiotherapy.