Prognostic value of the ratio of pretreatment carcinoembryonic antigen to tumor volume in rectal cancer

Background: As a commonly used biomarker in rectal cancer (RC), the prognostic value of carcinoembryonic antigen (CEA) remains underexplored. This study aims to evaluate the prognostic value of pretreatment CEA/tumor volume in RC. Methods: This retrospective study included patients who underwent pretreatment magnetic resonance imaging (MRI) with histologically confirmed primary rectal adenocarcinoma from November 2012 to April 2018. Patients were divided into high-risk and low-risk groups according to the median values of CEA/Dia(path) (CEA to pathological diameter), CEA/Dia(MRI) (CEA to MRI tumor diameter), and CEA/Vol(MRI) (CEA to MRI tumor volume). Cox regression analysis was utilized to determine the prognostic value of CEA, CEA/Dia(path), CEA/Dia(MRI), and CEA/Vol(MRI). Stepwise regression was used to establish nomograms for predicting disease-free survival (DFS) and overall survival (OS). Predictive performance was estimated by using the concordance index (C-index) and area under curve receiver operating characteristic (AUC). Results: A total of 343 patients [median age 58.99 years, 206 (60.06%) males] were included. After adjusting for patient-related and tumor-related factors, CEA/Vol(MRI) was superior to CEA, CEA/Dia(path), and CEA/Dia(MRI) in distinguishing high-risk from low-risk patients in terms of DFS [hazard ratio (HR) =1.83; P=0.010] and OS (HR =1.67; P=0.048). Subanalysis revealed that CEA/Vol(MRI) stratified high death risk in CEA-negative individuals (HR = 2.50; P=0.038), and also stratified low recurrence risk in CEA-positive individuals (HR =2.06; P=0.024). In the subanalysis of stage II or III cases, the highest HRs and the smallest P values were observed in distinguishing high-risk from low-risk patients according to CEA/Vol(MRI) in terms of DFS (HR =2.44; P=0.046 or HR =2.41; P=0.001) and OS (HR =1.96; P=0.130 or HR =2.22; P=0.008). The nomograms incorporating CEA/Vol(MRI) showed good performance, with a C- index of 0.72 [95% confidence interval (CI): 0.68-0.79] for DFS and 0.73 (95% CI: 0.68-0.80) for OS. Conclusions: Higher CEA/Vol(MRI) was associated with worse DFS and OS. CEA/Vol(MRI) was superior to CEA, CEA/Diapath, and CEA/Dia(MRI) in predicting DFS and OS. Pretreatment CEA/Vol(MRI) may facilitate risk stratification and treatment decision-making.