Abstract
PurposeInflammation predisposes to tumorigenesis by damaging DNA, stimulating angiogenesis and potentiating pro-proliferative and anti-apoptotic processes. The aim of this study was to investigate whether pre-treatment biomarkers of systemic inflammation are associated with survival outcomes in endometrial cancer. Patients and methodsWomen with endometrial cancer were recruited to a prospective database study. Pre-treatment systemic markers of inflammation, including C-reactive protein (CRP), Glasgow Prognostic Score and lymphocyte-based ratios [neutrophil-lymphocyte ratio (NMR), monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII)], were analysed in relation to overall, endometrial cancer-specific and recurrence-free survival using Kaplan-Meier estimation and multivariable Cox regression. ResultsIn total, 522 women of mostly White British ethnicity, with a median age of 66 years (interquartile range (IQR), 56, 73) and BMI of 32 kg/m2 (IQR 26, 39) were included in the analysis. Most had low-grade (67.2%), early-stage (85.4% stage I/II), endometrioid (74.5%) tumors. Women with pre-treatment CRP ≥5.5 mg/L had a 68% increase in overall (adjusted HR = 1.68, 95% CI 1.00–2.81, p = 0.049) and a two-fold higher cancer-specific mortality risk than those with CRP <5.5 mg/L (adjusted HR = 2.04, 95%CI 1.03–4.02, p = 0.04). Absolute lymphocyte count, NLR, MLR and SII were associated with adverse clinico-pathologic factors, but not overall, cancer-specific or recurrence-free survival in the multivariable analysis. ConclusionIf confirmed in an independent cohort, CRP may offer a simple, low-cost test to refine pre-treatment risk assessment and guide personalised care in endometrial cancer. Our participants were mostly of White British ethnicity and further studies are needed to confirm the utility of CRP as a prognostic biomarker in other populations.
Highlights
UK, with similar trends reported in other high income countries [2]
Our participants were mostly of White British ethnicity and further studies are needed to confirm the utility of C-reactive protein (CRP) as a prognostic biomarker in other populations
neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) and systemic immune inflammation index (SII) were associated with aggressive tumor parameters including stage, histology, grade, lymphovascular space invasion (LVSI) and deep myometrial invasion, but when these and clinical prognostic factors were controlled for, there was no evidence that lymphocyte-based scores are associated with overall, cancerspecific or recurrence-free survival
Summary
Accurate endometrial cancer risk assessment is fundamental to ensuring women receive appropriate evidence-based care [4]. Clinico-pathological risk assessment is based on tumor parameters, including International Federation of Gynaecology and Obstetrics (FIGO) surgical stage, tumor grade and histology, lymphovascular space invasion and depth of myometrial invasion [5,6]. The molecular classification of endometrial cancer holds great promise for improving risk stratification beyond these standard clinico-pathological features [7]. There is emerging evidence that prognosis is influenced by factors other than traditional clinico-pathological parameters, and that these may help to refine endometrial cancer risk assessment [4,8,9,10]
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