Cytokeratin 20 positive circulating tumor cells are a marker for response after neoadjuvant chemoradiation but not for prognosis in patients with rectal cancer

Abstract

BackgroundSeveral studies have shown, that circulating tumor cells (CTC) have a negative prognostic value in colorectal cancer patients. Aim of this study was to evaluate the role of CTC in specifically rectal cancer patients regarding the influence on overall survival and to elucidate the impact of CTC in predicting response after chemoradiation (RCTX).MethodsIn this prospective monocentric study 267 patients with rectal cancer were included. Patients with locally advanced tumors were treated with RCTX followed by surgery. The primary endpoints were: Evaluation of CTC at the time of surgery and correlation with main tumor characteristics, response to neoadjuvant RCTX and overall survival (OS). CTC were detected in the blood using CK20 RT-PCR.ResultsSixty-three patients were treated with neoadjuvant RCTX. In 46.8 % of the patients receiving neoadjuvant RCTX CTC were detected, which was significantly higher than in the group without RCTX (p = 0.002). Histopathologic regression after RCTX was evident in 27.8 % of the patients. In the subgroup of responders after RCTX we found CTC at a significantly lower rate than in non-responders (p = 0.03). No significant association was found between CTC detection and tumor characteristics and OS. The OS was significantly improved for responders compared to non-responders (p = 0.007).ConclusionsResponders after neoadjuvant RCTX had a lower incidence of CTC compared to non-responders, which might be a result of effective systemic and local treatment prior to surgery. Interestingly, detection of CTC did not correlate with tumor stage and OS, which is in contrast to previous reports of patients with colon cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1989-z) contains supplementary material, which is available to authorized users.

Detection of circulating tumor cells with CK20 RT-PCR is an independent negative prognostic marker in colon cancer patients – a prospective study

“…We included in our study exclusively patients with colon cancer as we have previously reported that in rectal cancer DTC and CTC have no prognostic influence on OS [12]. In accordance to our findings several other groups have also described that in rectal cancer CTC are not a prognostic factor for OS [30–32].…”

“…We have previously shown that in rectal cancer patients CTC detection by CK20 expression is not a prognostic marker, but a marker for response to neoadjuvant chemoradiation [12]. This finding even more stresses the biological differences and distinct modes of metastasis of colon and rectal cancer, which is underestimated in most clinical trials.…”

Predictive and Prognostic Molecular Biomarkers for Response to Neoadjuvant Chemoradiation in Rectal Cancer

“…CTCs were decreased in blood samples collected after nCRT from responders while no significant change was observed in non-responders [121]. Two studies assessed mRNA expression of cytokeratin-20 ( CK20) in blood mononuclear cells [122] and CEA/CK20/CD133 in peripheral blood [123] using RT-PCR to identify CTCs in rectal cancer. Although PCR-based CTC detection does not directly observe and enumerate CTCs and therefore might be less specific compared to immunocytologic methods [117], detection rates of these markers were significantly associated with nCRT response [122] and local recurrence [123].…”

Circulating Tumor Cells in Gastrointestinal Cancers: Current Status and Future Perspectives

“…Currently, there is limited evidence showing that CTCs detection at baseline can predict the response to systemic therapy in GI cancers (60,61,83,85,87,88,90,91,(95)(96)(97)(98). However, a few studies have demonstrated the predictive value of CTCs detection during chemotherapy (summarized in Table 2).…”