The Role of Cancer-Elicited Inflammatory Biomarkers in Predicting Early Recurrence Within Stage II–III Colorectal Cancer Patients After Curable Resection

BACKGROUND: Smoldering cancer-related inflammation attenuates chemotherapy efficacy and contributes to unsatisfactory outcome for patients of colorectal cancer (CRC). Various inflammation-based biomarkers were reported to predict the survival of the disease, however, it remains unclear which is the best inflammation-based biomarker. The aim of present study was to compare the prognostic role of those biomarkers and to establish superior survival score for post-recurrence survival in radically operative patients with stage II–III CRC. PATIENTS AND METHODS: Preoperative peripheral neutrophil, lymphocyte, monocyte, platelet, serum albumin (Alb), pre-Alb, and plasma fibrinogen (Fib) were detected in the discovery and validation cohort which included a total of 1533 stage II–III surgical CRC patients. We calculated and compared fourteen inflammation-based biomarkers for predicting recurrence-free survival (RFS) of the patients with stage II–III CRC. RESULTS: In this study, the platelet to lymphocyte ratio (PLR), lymphocyte to monocyte (LMR), systemic inflammation response index (SIRI), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), modified systemic inflammation score (mSIS), fibrinogen and neutrophil to lymphocyte ratio score (F-NLR), ratio of Alb to Fib (AFR), and ratio of Fib to pre-Alb (FPR) were all related to the RFS of the patients in both discovery and validation cohorts, however, only the LMR, SIRI, PNI, mSIS, F-NLR, AFR and FPR remained independent predictors for RFS in multivariate analysis. Both the C-index of the FPR (0.629 for 36 months) and the areas under the time-dependent receiver operating characteristic (ROC) curves (0.625 for 12 months, 0.641 for both 24 and 0.637 months) showed that it was superior to the other inflammation-based prognostic scores for predicting the RFS of stage II–III surgical CRC patients. Moreover, elevated FPR was significantly associated with unsatisfactory RFS regardless of TNM stage and primary tumor location. Stage II low FPR patients showed the best RFS regardless of chemotherapy. The better RFS was observed in chemotherapy-treated stage II high FPR patients than those without the treatment, and the outcomes of patients with treatment of XELOX, capecitabine and XELOX were superior to the other regimens to treat patients in stage III low- and high-FPR populations, respectively. Additionally, the carcinoembryonic antigen (CEA)-FPR combined score one (adjusted HR=2.764, 95% CI=2.129–3.589) and two (adjusted HR=3.543, 95% CI=2.317–5.420) were extremely associated with RFS of these patients, and the predicted AUC of the combined score for 12, 24 and 36 months were 0.657, 0.657 and 0.653 in stage II–III patients, which were superior to the single CEA and FPR, respectively. CONCLUSION: In conclusion, FPR is superior to the other inflammatory biomarkers as a useful recurrence indicator in stage II–III surgical CRC patients in terms of prognostic ability; it helps to choose the effective chemotherapy regimen and to increase the predicted efficacy of CEA and the combined CEA and FPR score could effectively predict recurrence of the patients.