Abstract
Simple SummaryOlder patients can have an increased expression of inflammatory cytokines due to ageing of the immune system. It is likely that older cancer patients with a low-grade inflammatory state are more at risk for an exaggerated inflammatory response to surgery and for poor outcome after surgery. The aim of this study was to examine whether preoperative inflammatory markers could be a predictor of overall survival in older patients undergoing oncologic surgery. In this prospective cohort study, a plasma level of C-reactive protein (CRP) ≥ 10 mg/L was a predictor of inferior three-year overall survival after oncologic surgery in older cancer patients, and also for the specific group of older patients with a colorectal tumor. Measuring preoperative plasma level of CRP might be useful in risk stratification for poor outcome after surgery in older cancer patients.Oncologic surgery results in substantially higher morbidity and mortality rates in older patients compared to younger patients, yet little is known about the relation between the preoperative inflammatory state and postoperative outcome in the specific group of older cancer patients. The aim of this study was to examine whether preoperative inflammatory markers could be a predictor of overall survival in older patients undergoing elective surgery for a solid malignant tumor. Patients 65 years and older undergoing surgery for a solid malignant tumor were included in a prospective cohort study. Inflammatory markers C-reactive protein (CRP), interleukin-1 beta (IL-1β), IL-6, IL10, IL-12 and tumor necrosis factor-alpha (TNF-α) were measured in plasma samples preoperatively. The main outcome was overall survival three years after surgery. Between 2010 and 2016, 328 patients with a median age of 71.5 years (range 65–89) were included. A significantly higher mortality rate three years after surgery, was found in patients with high preoperative plasma levels of CRP and IL-6 (p = 0.013 and p = 0.046, respectively). In multivariate analysis, corrected for variables such as age, disease stage, frailty, comorbidities, type of surgery and complications, a preoperative plasma level of CRP ≥ 10 mg/L was an independent prognostic factor for inferior overall survival three years after surgery (multivariate hazard ratio 1.50, 95% confidence interval 1.04–2.16, p = 0.031). Also, for the specific group of patients with colorectal cancer, a preoperative plasma level of CRP ≥ 10 mg/L was a prognostic factor for inferior survival three years after surgery (multivariate hazard ratio 2.40, 95% confidence interval 1.20–4.81, p = 0.014). Preoperative elevated plasma level of CRP is an independent unfavorable prognostic factor for overall survival three years after oncologic surgery. This gives more insight into the relationship between inflammation and survival in older cancer patients, and might contribute to risk stratification for poor outcome after surgery in older cancer patients.
Highlights
As the world-wide population is ageing, the incidence of cancer in older patients is increasing [1]
These studies are registered in the Dutch Clinical Trial Database at www.trialregister.nl: NL4219 (2010-07-22) and NL4441 (2014-06-01). Both cohort studies were approved by the Medical Ethical Committee of the University Medical Center Groningen (UMCG). Clinical data such as age, gender, disease stage, tumor type, comorbidities according to the Charlson Comorbidity Index (CCI), frailty according to the Groningen Frailty Indicator (GFI) were
In a study with 525 patients with colon cancer with a median follow-up time of 4.5 years, Kersten et al found that a preoperative C-reactive protein (CRP) of >30 mg/L was associated with inferior disease specific survival (HR 2.1 95% confidence intervals (95% CIs) (1.39–3.10))
Summary
As the world-wide population is ageing, the incidence of cancer in older patients is increasing [1]. With the increasing population of older people with cancer, more patients are in need of oncologic surgery. Ageing-related remodeling of the immune system in older patients results in a lowgrade inflammatory state with increased expression of cytokines [3]. It is likely that the combination of preoperatively elevated inflammatory markers and an increased inflammatory response to surgery makes older cancer patients more susceptible to poor outcome after surgery. It is already known that preoperatively elevated cytokine levels in older patients lead to a higher incidence of postoperative complications [6]. As complications increase mortality rates [7], it is plausible that the inflammatory state prior to surgery will influence survival after surgery in older cancer patients
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