Abstract

Background: Heterogeneous clinical and molecular characteristics are reported in colorectal cancer (CRC) with different tumor laterality. However, the outcome of left- and right-sided patients with stage I–III CRC and the role of chronic inflammation in survival differences between them remain unclear.Method: A prospective study including 1,181 surgical patients with stage I–III CRC was carried out to investigate the involvement of circulating fibrinogen-to-pre-albumin (Alb) ratio (FPR) and primary tumor sidedness in the clinical outcome of those patients. We further investigated the effect of FPR on adjuvant chemotherapy response and recurrence in stage III patients.Results: Our study showed that the right tumor location was significantly associated with poor recurrence-free survival (RFS) (p = 0.04, adjusted HR = 1.41, 95% CI = 1.02–1.94) and overall survival (OS) (p = 0.04, adjusted HR = 1.55, 95% CI = 1.01–2.38) only in the stage III disease. In these patients, T4 stage distribution (83.39 vs. 70.94%, p < 0.01) within right-sided cases was significantly higher than left-sided patients. Moreover, preoperative FPR within right-sidedness (p < 0.01), T4 stage (p < 0.05), and large cancer bulk (≥5 cm) (p < 0.05) subgroups was significantly elevated compared to their counterparts, and it was gradually rising following the increased cancer bulk (p trend < 0.01). High-FPR distribution (52.30 vs. 27.00%, p < 0.01) within right-sided patients with the stage III disease was significantly higher than that in the left-sided cases. RFS (plog−rank < 0.01) and OS (plog−rank < 0.01) of the high-FPR patients were extremely inferior to the low-FPR cases, and the significant associations were observed when they were adjusted by other confounders including primary tumor location (p < 0.01, adjusted HR = 1.96, 95% CI = 1.42–2.70 for RFS; p < 0.01, adjusted HR = 2.44, 95% CI = 1.59–3.75 for OS). Additionally, RFS of adjuvant chemotherapy-treated high-FPR patients was superior to the patients without chemotherapy (plog−rank = 0.01) but was inferior to the low-FPR patients undergoing the treatment, especially in the 5-FU- and XELOX-treated subgroup.Conclusion: These findings indicate that chronic high-grade inflammation weakens chemotherapy efficacy and contributes to the poor prognosis of stage III surgical CRC patients.

Highlights

  • Colorectal cancer (CRC) is a kind of heterogeneous malignancy with different clinical options and diverse therapeutic outcome [1, 2]

  • We further investigated the effect of fibrinogen-to-pre-albumin (Alb) ratio (FPR) on adjuvant chemotherapy response and recurrence in stage III patients

  • Our study showed that the right tumor location was significantly associated with poor recurrence-free survival (RFS) (p = 0.04, adjusted hazard ratio (HR) = 1.41, 95% confidence interval (CI) = 1.02–1.94) and overall survival (OS) (p = 0.04, adjusted HR = 1.55, 95% CI = 1.01–2.38) only in the stage III disease

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Summary

Introduction

Colorectal cancer (CRC) is a kind of heterogeneous malignancy with different clinical options and diverse therapeutic outcome [1, 2]. Our previous studies imply that the prognosis of bevacizumab-treated left-sided mCRC patients is better than the counterpart [12, 13] These findings reveal that tumor laterality can affect and predict the efficacy of target therapy within the advanced disease. Karim et al reported no overall survival (OS) and cancer-specific survival (CSS) difference between the right- and left-sided patients with stage I–III or III colon cancer [15]. A poor prognosis in terms of recurrence-free survival (RFS) and OS was reported in stage III right-sided colon cancer patients undergoing adjuvant chemotherapy [14, 17]. Heterogeneous clinical and molecular characteristics are reported in colorectal cancer (CRC) with different tumor laterality. The outcome of left- and right-sided patients with stage I–III CRC and the role of chronic inflammation in survival differences between them remain unclear

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