Abstract
ObjectiveThe aim of this study was to analyse the survival impact of primary tumor nodal status (N0/N+) in patients with resectable colorectal liver metastases (CLM), and to determine the value of circulating and disseminated tumor cells (CTCs/DTCs) in this setting.MethodsIn this prospective study of patients undergoing resection of CLM from 2008 to 2011, peripheral blood was analyzed for CTCs using the CellSearch System®, and bone marrow was sampled for DTC analyses just prior to hepatic resection. The presence of one or more tumor cells was scored as CTC/DTC-positive. Following resection of the primary tumor, the lymph nodes (LNs) were examined by routine histopathological examination.ResultsA total of 140 patients were included in this study; 38 patients (27.1%) were negative at the primary colorectal LN examination (N0). CTCs were detected in 12.1% of all patients; 5.3% of patients in the N0 group and 14.7% of patients in the LN-positive (N+) group (p = 0.156), with the LN-positive group (N+) consisting of both N1 and N2 patients. There was a significant difference in recurrence-free survival (RFS) when analysing the N0 group versus the N+ group (p = 0.007) and CTC-positive versus CTC-negative patients (p = 0.029). In multivariate analysis, CTC positivity was also significantly associated with impaired overall survival (OS) [p = 0.05], whereas DTC positivity was not associated with survival.ConclusionIn this cohort of resectable CLM patients, 27% had primary N0 colorectal cancer. Assessment of CTC in addition to nodal status may contribute to improved classification of patients into high- and low-risk groups, which has the potential to guide and improve treatment strategies.
Highlights
The association between N status and survival was quantified by hazard ratio (HR) with its 95% confidence interval (CI)
A T2 primary tumor was significantly more common in the N0 group (29.0% vs. 2.9% in the N? group, p = 0.001) and primary colon cancer had a higher frequency of N0 status than primary rectal cancer (p = 0.007)
The crude HR for N status of the primary tumor and recurrence-free survival (RFS) after resection of the colorectal liver metastases (CLM) was 1.95
Summary
Patients included in this study represent a subgroup from a prospective cohort study of 194 CLM patients referred to Oslo University Hospital for surgical treatment from May 2008 to December 2011 This cohort has been previously described in detail by Seeberg et al.[15] In order to obtain a homogenous study population of CLM patients with resectable liver metastases and reliable LN status for the present analysis, two patients without resection of their primary tumor, and unknown nodal status, were excluded. Thirteen of the 60 node-negative patients had received neoadjuvant radiotherapy and/or chemotherapy before resection of the primary tumor, and were excluded because of uncertain nodal status. Unresectable due to disease progression at first stage or after the first stage of a planned twostage hepatectomy n=19
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