Abstract
The aim of the present study was to investigate the association of the pre-treatment C-reactive protein (CRP) plasma level with survival outcomes in a cohort of 423 consecutive patients with locally advanced rectal cancer treated with neo-adjuvant radiochemotherapy followed by surgical resection. To evaluate the prognostic value of the CRP level for clinical endpoints recurrence-free survival (RFS), local-regional control (LC), metastases-free survival (MFS), and overall survival (OS), uni- and multivariate Cox regression analyses were applied, and survival rates were calculated using Kaplan–Meier analysis. The median follow-up time was 73 months. In univariate analyses, the pre-treatment CRP level was a significant predictor of RFS (hazard ratio (HR) 1.015, 95% CI 1.006–1.023; p < 0.001), LC (HR 1.015, 95% CI 1.004–1.027; p = 0.009), MFS (HR 1.014, 95% CI 1.004–1.023; p = 0.004), and OS (HR 1.016, 95% CI 1.007–1.024; p < 0.001). Additionally, univariate analysis identified the MRI circumferential resection margin (mrCRM) and pre-treatment carcinoembryonic antigen (CEA) as significant predictor of RFS (HR 2.082, 95% CI 1.106–3.919; p = 0.023 and HR 1.005, 95% CI 1.002–1.008; p < 0.001). Univariate analysis also revealed a significant association of the mrCRM (HR 2.089, 95% CI 1.052–4.147; p = 0.035) and CEA (HR 1.006, 95% CI 1.003–1.008; p < 0.001) with MFS. Age and CEA were prognostic factors for OS (HR 1.039, 95% CI 1.013–1.066; p = 0.003 and HR 1.005, 95% CI 1.002–1.008; p < 0.001). In multivariate analysis that included parameters with a p-level < 0.20 in univariate analysis, the pre-treatment CRP remained a significant prognostic factor for RFS (HR 1.013, 95%CI 1.001–1.025; p = 0.036), LC (HR 1.014, 95% CI 1.001–1.027; p = 0.031), and MFS (HR 1.013, 95% CI 1.000–1.027; p = 0.046). The results support the hypothesis that an elevated pre-treatment CRP level is a predictor of poor outcome. If confirmed by additional studies, this easily measurable biomarker could contribute to the identification of patients who might be candidates for more aggressive local or systemic treatment approaches or the administration of anti-inflammatory drugs.
Highlights
Colorectal cancer (CRC) is one of the most commonly occurring cancers worldwide with a remarkable increase in incidence among adults younger than 50 years [1,2]
The pre-treatment C-reactive protein (CRP) level was significantly correlated with body mass index (BMI, p = 0.005) and initial tumor stage (T1/2 vs T3 vs T4, p < 0.001), and the involvement of the circumferential resection margin defined on the magnetic resonance imaging; in addition, a significant association between the pre-treatment and post-treatment CRP level was observed (p < 0.001)
To date, only 1 series has examined the prognostic role of the pre-treatment plasma CRP for survival outcomes in rectal cancer patients treated with neo-adjuvant radiochemotherapy (nRCT)
Summary
Colorectal cancer (CRC) is one of the most commonly occurring cancers worldwide with a remarkable increase in incidence among adults younger than 50 years [1,2]. Previous studies have compared preoperative versus postoperative radiochemotherapy (RCT) demonstrating that preoperative therapy is associated with a significant reduction in local recurrence and treatment-associated toxicity, OS is similar in both groups. Some studies have indicated that preoperative radiotherapy (RT) or RCT is associated with increased rates of sphincter preservation [5,6,7]. In a previous analysis by our study group, we analyzed further patient- and tumor-associated routine parameters in low rectal cancer affecting the sphincter-preserving surgery rate. The parameters age, lymphocyte count and interval between nRCT and surgery at the beginning of an oncologic treatment contributed to the sphincter-preservation rate and could contribute to the identification of patients who could benefit from a more aggressive treatment approach [8]
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