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Assessing the prognostic value of preoperative carcinoembryonic antigen-specific T-cell responses in colorectal cancer.

ABSTRACT: Current dogma suggests that tumor-reactive IFN-?-producing (TH1-type) T-cells are beneficial to patient outcome; however, the clinical consequence of these responses with respect to long-term prognosis in colorectal cancer (CRC) is not understood. Here, we compared the utility of preoperative, peripheral blood-derived IFN-?(+) T-cell responses specific to carcinoembryonic antigen (CEA), 5T4, or control antigens (n = 64) with tumor staging and clinical details (n = 87) in predicting five-year outcome of CRC patients who underwent resection with curative intent. Although disease recurrence was more likely in patients with stage III tumors, the presence of preoperative, CEA-specific IFN-?-producing T-cells identified patients at a statistically significantly greater risk of tumor recurrence following surgical resection, irrespective of tumor stage (odds ratio = 5.00, 95% confidence interval = 1.96 to 12.77, two-sided P <.001). Responses to other antigens, including 5T4, did not reflect outcome. Whilst these results initially appear surprising, they could improve prognostication and help redirect adjuvant treatments.

SUBMITTER: Scurr MJ

PROVIDER: S-EPMC4394893 | biostudies-other | 2015 Apr

REPOSITORIES: biostudies-other

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Assessing the prognostic value of preoperative carcinoembryonic antigen-specific T-cell responses in colorectal cancer.

Scurr Martin J MJ Brown Clare M CM Costa Bento Diana F DF Betts Gareth J GJ Rees Brian I BI Hills Robert K RK Gallimore Awen A Godkin Andrew A

Journal of the National Cancer Institute 20150209 4

Current dogma suggests that tumor-reactive IFN-γ-producing (TH1-type) T-cells are beneficial to patient outcome; however, the clinical consequence of these responses with respect to long-term prognosis in colorectal cancer (CRC) is not understood. Here, we compared the utility of preoperative, peripheral blood-derived IFN-γ(+) T-cell responses specific to carcinoembryonic antigen (CEA), 5T4, or control antigens (n = 64) with tumor staging and clinical details (n = 87) in predicting five-year out ...[more]

PMID: 25669203

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Project description:BackgroundSerum carcinoembryonic antigen (CEA) is an important biomarker for diagnosis, prognosis, recurrence, metastasis monitoring, and the evaluation of the effect of chemotherapy in colorectal cancer (CRC). However, few studies have focused on the role of early postoperative CEA in the prognosis of stage II CRC.MethodsPatients with stage II CRC diagnosed between January 2007 and December 2015 were included. Receiver operating characteristic (ROC) curves were used to obtain the cutoff value of early postoperative CEA, CEA ratio and CEA absolute value. The areas under curves (AUCs) were used to estimate the predictive abilities of the CEA and T stage. The stepwise regression method was used to screen the factors included in the Cox regression analysis. Before and after propensity score (PS) - adjusted Cox regression and sensitivity analysis were used to identify the relationship between early postoperative CEA and prognosis. Meta-analysis was performed to verify the results. Kaplan-Meier survival curves were used to estimate the effects of CEA on prognosis.ResultsWe included 1081 eligible patients. ROC curves suggested that the cutoff value of early postoperative CEA was 3.66 ng/ml (P <0.001) and the AUC showed early postoperative CEA was the most significant prognostic marker in stage II CRC (P = 0.0189). The Cox regression and sensitivity analysis before and after adjusting for PS both revealed elevated early postoperative CEA was the strongest independent prognostic factor of OS, DFS, and CSS (P < 0.001). Survival analysis revealed that patients with elevated early postoperative CEA had lower OS (53.62% VS 84.16%), DFS (50.03% VS 86.75%), and CSS (61.77% VS 90.30%) than patients with normal early postoperative CEA (P < 0.001). When the postoperative CEA was positive, the preoperative CEA level showed no significant effect on the patient's prognosis (all P-values were > 0.05). Patients with a CEA ratio ≤0.55 or CEA absolute value ≤-0.98 had a worse prognosis (all P-values were < 0.001). Survival analysis suggested that adjuvant chemotherapy for stage II CRC patients with elevated early postoperative CEA may improve the CSS (P = 0.040).ConclusionsEarly postoperative CEA was a better biomarker for prognosis of stage II CRC patients than T stage and preoperative CEA, and has the potential to become a high-risk factor to guide the prognosis and treatment of stage II CRC patients.

Project description:ImportanceGuidelines recommend measuring preoperative carcinoembryonic antigen (CEA) in patients with colon cancer. Although persistently elevated CEA after surgery has been associated with increased risk for metastatic disease, prognostic significance of elevated preoperative CEA that normalized after resection is unknown.ObjectiveTo investigate whether patients with elevated preoperative CEA that normalizes after colon cancer resection have a higher risk of recurrence than patients with normal preoperative CEA.Design, setting, and participantsThis retrospective cohort analysis was conducted at a comprehensive cancer center. Consecutive patients with colon cancer who underwent curative resection for stage I to III colon adenocarcinoma at the center from January 2007 to December 2014 were identified.ExposuresPatients were grouped into 3 cohorts: normal preoperative CEA, elevated preoperative but normalized postoperative CEA, and elevated preoperative and postoperative CEA.Main outcomes and measuresThree-year recurrence-free survival (RFS) and hazard function curves over time were analyzed.ResultsA total of 1027 patients (461 [50.4%] male; median [IQR] age, 64 [53-75] years) were identified. Patients with normal preoperative CEA had 7.4% higher 3-year RFS (n = 715 [89.7%]) than the combined cohorts with elevated preoperative CEA (n = 312 [82.3%]) (P = .01) but had RFS similar to that of patients with normalized postoperative CEA (n = 142 [87.9%]) (P = .86). Patients with elevated postoperative CEA had 14.9% lower RFS (n = 57 [74.5%]) than the combined cohorts with normal postoperative CEA (n = 857 [89.4%]) (P = .001). The hazard function of recurrence for elevated postoperative CEA peaked earlier than for the other cohorts. Multivariate analyses confirmed that elevated postoperative CEA (hazard ratio [HR], 2.0; 95% CI, 1.1-3.5), but not normalized postoperative CEA (HR, 0.77; 95% CI, 0.45-1.30), was independently associated with shorter RFS.Conclusions and relevanceElevated preoperative CEA that normalizes after resection is not an indicator of poor prognosis. Routine measurement of postoperative, rather than preoperative, CEA is warranted. Patients with elevated postoperative CEA are at increased risk for recurrence, especially within the first 12 months after surgery.

Dataset Information

Assessing the prognostic value of preoperative carcinoembryonic antigen-specific T-cell responses in colorectal cancer.

Publications

Assessing the prognostic value of preoperative carcinoembryonic antigen-specific T-cell responses in colorectal cancer.

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