Abstract
BACKGROUND: The clinical factors that accurately predict the response to preoperative treatment in rectal cancer were yet unknown. The carcinoembryonic antigen (CEA) clearance pattern during neoadjuvant treatment has been developed and the predictive value explored in rectal cancer patients with elevated CEA levels (> 5 ng/mL). METHODS: The training cohort was derived from the FOWARC prospective phase III trial, and 71/483 eligible patients were included. The validation cohort consisted of 75/587 consecutive rectal cancer patients from Xiangya Hospital between 2014 and 2015. The kinetic changes in serum CEA were measured at different time points during the neoadjuvant treatment. An exponential trend line was drawn using the CEA values. The patients were categorized into two groups based on the R(2) value of the trend line, which indicates the correlation coefficient between the exponential graph and measured CEA values: exponential decrease group (0.9 < R(2) ≤ 1.0) and non-exponential decrease group (R(2) ≤ 0.9). RESULTS: In multivariate analysis, the patients in the CEA exponential decrease group had significantly high adequate rate of downstaging (ypT0-2N0M0), and pathologic complete response (pCR) rates after neoadjuvant treatment in the training cohort. The predictive values of the CEA clearance pattern for tumor downstaging and pCR were further confirmed in an independent validation cohort. CONCLUSIONS: The CEA clearance pattern was an independent predictor of tumor response to neoadjuvant treatment in patients with rectal cancer. It might serve as an adjunct in the assessment of complete clinical response and guide individualized treatment strategies. TRIAL REGISTRATION: NCT01211210.