Published online Jan 21, 2022. doi: 10.12998/wjcc.v10.i3.899
Peer-review started: July 19, 2021
First decision: October 3, 2021
Revised: October 21, 2021
Accepted: December 25, 2021
Article in press: December 25, 2021
Published online: January 21, 2022
The roles of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9) in monitoring the patient response to chemotherapy for metastatic colorectal cancer (mCRC) are not clearly defined, and inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII), have been sparsely investigated for this purpose.
To aim of this study was to evaluate the relationship between the kinetics of CEA, CA19-9, NLR, LMR, PLR and SII in serum and patient response to chemotherapy estimated by computed tomography (CT) in patients with unresectable mCRC.
Patients with mCRC treated with a 1st-line and 2nd-line chemotherapy underwent at least 3 whole-body spiral CT scans during response monitoring according to the Response Evaluation Criteria in Solid Tumour 1.1 (RECIST 1.1), and simultaneous determination of CEA, CA19-9, neutrophil, lymphocyte, platelet and monocyte levels was performed. The kinetics of changes in the tumour markers and inflammatory indices were calculated as the percentage change from baseline or nadir, while receiver operating characteristic curves were drawn to select the thresholds to define patients with progressive or responsive disease with the highest sensitivity (Se) and specificity (Sp). The correlation of tumour marker kinetics with inflammatory index changes and RECIST response was determined by univariate and multivariate logistic regression analysis and the clinical utility index (CUI).
A total of 102 patients with mCRC treated with chemotherapy were included. Progressive disease (PD), defined as a CEA increase of 25.52%, resulted in an Se of 80.3%, an Sp of 84%, a good CUI negative [CUI (Ve-)] value of 0.75 and a good fraction correct (FC) value of 81.2; at a CEA cut-off of -60.85% with an Se of 100% and an Sp of 35.7% for PD, CT could be avoided in 25.49% of patients. The 21.49% CA19-9 cut-off for PD had an Se of 66.5%, an Sp of 87.4%, an acceptable CUI (Ve-) value of 0.65 and an acceptable FC value of 75. An NLR increase of 11.5% for PD had an Se of 67% and an Sp of 66%; a PLR increase of 5.9% had an Se of 53% and an Sp of 69%; an SII increase above -6.04% had an Se of 72% and an Sp of 63%; and all had acceptable CUI (Ve-) values at 0.55. In the univariate logistic regression analysis, CEA (P < 0.001), CA19-9 (P < 0.05), NLR (P < 0.05), PLR (P < 0.05) and SII (P < 0.05) were important predictors of tumour progression, but in the multivariate logistic regression analysis, CEA was the only independent predictor of PD (P < 0.05).
CEA is a useful marker for monitoring the chemotherapy response of patients with unresectable mCRC and could replace a quarter of CT examinations. CA19-9 has poorer diagnostic characteristics than CEA but could be useful in some clinical circumstances, particularly when CEA is not increased. Dynamic changes in the inflammatory indices NLR, PLR and SII could be promising for further investigation as markers of the chemotherapy response.
Core Tip: A carcinoembryonic antigen increase of 24.5% discriminates progressive disease (PD) from disease control with 80.3% sensitivity (Se) and 84% specificity (Sp) and good clinical utility index negative [CUI (Ve-)] and fraction correct (FC) values, while a reduction of -60% exclude PD with 100% Se and 37.5% Sp allowing for a 25.49% reduction in control CT examinations of unresectable metastatic colorectal cancer patients. The carbohydrate antigen level cut-off for PD was 21.49% with 66.5% Se, 87.4% Sp and acceptable CUI (Ve-) and FC values. A neutrophile-to-lymphocyte ratio increase by 11.5%, a platelet-to-lymphocyte ratio increase by 5.9%, a systemic inflammatory-immune index increase above -6.04% had acceptable CUI (Ve-) values.