C-Reactive Protein as Predictive Biomarker for Response to Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer: A Retrospective Study

SIMPLE SUMMARY: Most patients with locally advanced rectal cancer present resistance or a moderate response to neoadjuvant chemoradiotherapy (nCRT), which is considered the standard of care. To select patients who could benefit from nCRT, while avoiding unnecessary treatment-induced toxicity and surgery-associated morbidity, it is urgent to find biomarkers of response to chemoradiotherapy. Therefore, the aim of our retrospective study was to assess the potential of classical blood analytes collected before chemoradiotherapy as biomarkers of response to treatment and prognostics in locally advanced rectal cancer. Our results identified C-reactive protein ≤3.5 as a strong independent predictor of response to treatment and an independent predictor of disease-free survival (DFS) and overall survival (OS). Additionally, platelets were found to be independent predictors of DFS and OS and hemoglobin of DFS. These data might contribute to the personalization of rectal cancer treatment by guiding clinicians in decision-making regarding the best treatment strategy for each patient. ABSTRACT: The standard of care for the treatment of locally advanced rectal cancer is neoadjuvant chemoradiotherapy (nCRT) followed by surgery, but complete response rates are reduced. To find predictive biomarkers of response to therapy, we conducted a retrospective study evaluating blood biomarkers before nCRT. Hemoglobin (Hg), C-reactive protein (CRP), platelets, carcinoembryonic antigen, carbohydrate antigen 19.9 levels, and neutrophil/lymphocyte ratio were obtained from 171 rectal cancer patients before nCRT. Patients were classified as responders (Ryan 0–1; ycT0N0), 59.6% (n = 102), or nonresponders (Ryan 2–3), 40.3% (n = 69), in accordance with the Ryan classification. A logistic regression using prognostic pretreatment factors identified CRP ≤ 3.5 (OR = 0.05; 95%CI: 0.01–0.21) as a strong independent predictor of response to treatment. Multivariate analysis showed that CRP was an independent predictor of disease-free survival (DFS) (HR = 5.48; 95%CI: 1.54–19.48) and overall survival (HR = 6.10; 95%CI 1.27–29.33) in patients treated with nCRT. Platelets were an independent predictor of DFS (HR = 3.068; 95%CI: 1.29–7.30) and OS (HR= 4.65; 95%CI: 1.66–13.05) and Hg was revealed to be an independent predictor of DFS (HR = 0.37; 95%CI: 0.15–0.90) in rectal cancer patients treated with nCRT. The lower expression of CRP is independently associated with an improved response to nCRT, DFS, and OS.