Post-operative inflammation in cancer patients can be modulated by drugs and diets, but evidence on its prognostic role, which would be crucial for personalized treatment and surveillance schemes, remains rather limited. We aimed to systematically review and meta-analyse studies on the prognostic value of post-operative C-reactive protein (CRP)-based inflammatory biomarkers among patients with colorectal cancer (CRC) (PROSPERO#: CRD42022293832). PubMed, Web of Science and Cochrane databases were searched until February 2023. Studies reporting associations between post-operative CRP, Glasgow Prognostic Score (GPS) or modified Glasgow Prognostic Score (mGPS) with overall survival (OS), CRC-specific survival (CSS) and recurrence-free survival (RFS) were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) for the predictor-outcome associations were pooled using R-software, version 4.2. Sixteen studies (n = 6079) were included in the meta-analyses. Elevated post-operative CRP was a predictor of poor OS, CSS and RFS compared with low CRP levels [HR (95% CI): 1.72 (1.32– 2.25); 1.63 (1.30– 2.05); 2.23 (1.44– 3.47), respectively]. A unit increase in post-operative GPS predicted poor OS [HR (95% Cl): 1.31 (1.14– 1.51)]. Moreover, a unit increase in post-operative mGPS was associated with poor OS and CSS [HR (95% Cl): 1.93 (1.37– 2.72); 3.16 (1.48– 6.76), respectively]. Post-operative CRP-based inflammatory biomarkers have a significant prognostic role for patients with CRC. Prognostic value of these easy-to-obtain routine measurements thereby seems to outperform most of the much more complex blood- or tissue-based predictors in the current focus of multi-omics-based research. Future studies should validate our findings, establish optimal time for biomarker assessment and determine clinically useful cut-off values of these biomarkers for post-operative risk-stratification and treatment-response monitoring.

Post-surgery blood-based biomarkers may be useful for guiding treatment and surveillance decisions among colorectal cancer (CRC) patients. However, most candidate biomarkers provide little if any predictive value beyond stage at diagnosis. We aimed to investigate the independent prognostic value of post-operative serum C-reactive protein (CRP), a highly sensitive biomarker of inflammation, for long-term CRC outcomes in two large patient cohorts. CRP levels were measured from serum samples of CRC patients collected ≥1 month post-surgery in the German DACHS (n = 1416) and the UK Biobank (n = 1149) cohorts. Associations of post-operative CRP with overall survival (OS) and CRC-specific survival (CSS) were assessed using Cox regression and presented as hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for key sociodemographic and clinical covariates. In both cohorts, consistent strong dose-response relationships between post-operative CRP and both OS and CSS were observed. Adjusted HRs (95% CI) for CRP >10 versus <3 mg/l were 1.93 (1.58-2.35) and 2.70 (2.03-3.59) in the DACHS cohort, and 2.70 (1.96-3.71) and 2.61 (1.83-3.72) in the UK Biobank cohort, respectively. Associations between post-operative CRP and OS were particularly strong among younger patients (<65 years at diagnosis; P value for interaction by age <0.01). Serum CRP determined a month or more after surgery may be useful as a strong independent prognostic biomarker for guiding therapeutic decisions and for surveillance of the course of disease of CRC patients, particularly those <65 years of age at diagnosis.

According to recent evidence, the prognostic value of Vitamin D (VitD) status for colorectal cancer (CRC) patients might be confined to patients with the GG genotype of Cdx2, a functional polymorphism of the VitD receptor gene. We aimed to validate these findings in a cohort of CRC patients. Post-operative serum 25-hydroxyvitamin D concentration was determined by mass spectrometry and Cdx2 genotyping was performed from blood or buccal swabs using standard methods. Joint associations of VitD status and Cdx2 with overall survival (OS), CRC-specific survival (CSS), recurrence-free survival (RFS), and disease-free survival (DFS) were assessed using Cox regression. For patients with GG genotype, adjusted hazard ratios (95% confidence interval) for the associations of sufficient compared with deficient VitD were 0.63 (0.50–0.78), 0.68 (0.50–0.90), 0.66 (0.51–0.86), and 0.62 (0.50–0.77) for OS, CSS, RFS, and DFS, respectively. These associations were weaker and not statistically significant for the AA/AG genotype. Interaction between VitD status and genotype did not reach statistical significance. VitD deficiency is an independent predictor of poorer survival, particularly for the GG Cdx2 carriers, suggesting a potential role of VitD supplementation according to VitD status and genotype, which should be evaluated in randomised trials.

Background: Post-operative anaemia is linked to iron deficiency. We investigated the prognostic value of post-operative iron biomarkers in colorectal cancer (CRC). Methods: Ferritin, transferrin, iron, and transferrin saturation (TS%) were measured from blood collected at a single time-point post-surgery in 2769 CRC patients. Associations between iron biomarkers with cancer-specific survival (CSS) and overall survival (OS) were assessed using Cox regression with hazard ratios (HR), stratified by post-operative time of blood collection (<1-month/≥1-month). Results: After a median follow-up of 9.5 years, 52.6% of patients had died. For iron biomarkers assessed <1-month post-surgery, higher compared to normal TS% was associated with shorter CSS (HR [95% CI] = 2.36 [1.25–4.46]), and higher iron levels with better OS (upper vs. median tertile: HR [95% CI] = 0.79 [0.65–0.97]). When assessed ≥1-month post-surgery, elevated ferritin was associated with poor CSS (high vs. normal: HR [95% CI] = 1.44 [1.10–1.87]), and low TS% with worse CSS (low vs. normal: HR [95% CI] = 1.60 [1.24–2.06]). Similar but weaker associations were observed for OS. Conclusion: Monitoring of serum ferritin and TS% beyond 1-month post-surgery may be relevant for risk stratification of patients with operable CRC. Future studies should validate our findings.

Background: Low vitamin D status and inflammation are associated with poor prognosis among colorectal cancer (CRC) patients. We assessed the efficacy of personalized vitamin D ₃ supplementation (VIDS) for reducing inflammation in patients with low vitamin D status. Methods: In an ongoing randomized double-blind, placebo-controlled trial in Germany, CRC patients who underwent surgery in the past year and had serum 25-hydroxyvitamin D levels < 60 nmol/L were randomly assigned to either a personalized loading dose of VIDS, followed by a maintenance dose of 2000 IU/day or a placebo for 12 weeks. Changes in serum interleukin-6 (IL-6), interferon-gamma (IFN-γ), and matrix metalloproteinase (MMP-1) were compared at the end of trial among 126 patients (65 in the placebo and 61 in the intervention group). Results: The VIDS group exhibited 39.3% reduction in IL-6 levels compared to the placebo group (95% CI: −54.9% to −18.2%; p = 0.001). The reductions observed in IFN-γ and MMP-1 due to VIDS were not statistically significant (−6.7%; p = 0.69 and −5.4%; p = 0.23, respectively). Conclusion: In CRC patients with low vitamin D status, VIDS reduces serum IL-6, a pro-inflammatory biomarker associated with poor prognosis. Further research should explore a potential supportive therapeutic role of VIDS in managing inflammation and improving CRC outcomes. [Words: 200 ].