gms | German Medical Science

Background: Even though therapeutic efficiency advanced greatly in recent decades, colorectal carcinoma still poses one of the most common malignancies in the western world; almost 90% of patient deaths are due to metastasis.

Many recent studies have shown that detection of circulating (CTC – found in the peripheral bloodstream)- and disseminated (DTC – found in bone marrow blood) tumor cells have a significant negative prognostic value in patients with colorectal carcinoma. However very few studies differentiate between anatomical entities in terms of rectum and colon. This is the largest series of patients discriminating between colon and rectal cancer patients with regard to the detection of disseminated or circulating tumor cells.

Materials and methods: In this prospective study 566 patients (rectal cancer n=267, colon cancer n=299) with histological diagnosed colorectal cancer were included in this study. All patients underwent complete tumor resection. In the rectal cancer cohort 63 patients were treated with neoadjuvant RCTX due to locally advanced disease and then subdivided into responders and non-responders. Mean clinical follow up was 55 months. Of each patient a blood sample was taken instantly before surgery took place. Prior to the detection of CTC mRNA of mononuclear cells (MNC) was extracted and CK20 RT-PCR was performed. In addition to RT-PCR, DTC were also detected with immunocytochemistry using pancytokeratin antibody as well as anti-EpCAM antibody. The primary endpoints were: Evaluation of CTC/ DTC at the time of surgery and correlation with main tumor characteristics and overall survival.

Results: The mean age of the patients was 67.4 years (29-92) for colon carcinoma and 64.4 years (30-90) for rectal carcinoma patients, respectively. The mean overall survival (OS) was 78% and 60% and a strong correlation between UICC classification and OS could be observed. The overall detection rate of CK20 positive CTC with CK20 RT-PCR was 32.4% (97/299) for colon carcinoma patients and 31.6% (80/253) in rectal carcinoma patients. The detection of CK20 positive CTC was a strong negative prognostic parameter in colon carcinoma patients. The OS in CTC positive patients was 68% in comparison to 85% in the cohort with absent CTC (p=0.002). In contrast to these findings, in rectal cancer patients no significant association was found between CTC detection and OS. Though the OS was significantly improved for responders compared to non-responders (p=0.007).

The OS of patients with detectable DTC in the bone marrow blood of colon carcinoma patients was not different from patients without DTC (p=0.098).

Conclusion: In this present study we could prove that rectal carcinoma patients responding to neoadjuvant RCTX had a lower incidence of CTC compared to non-responders. This 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 in these patients, which is in contrast to the analyzed cohort of colon carcinoma patients. Here detection of CTC was a strong negative prognostic marker in terms of the OS. Further detection of DTC in colon and rectal carcinoma patients did influence the OS.