Prognostic impact of serum albumin level and metastatic lymph node ratio in colorectal cancer

Objective: Colorectal cancer is the third most common type of cancer in both men and women worldwide. As the stage of the disease advances, the expected five-year survival rate decreases. Predicting poor prognosis is of clinical importance to ensure that patients receive optimal treatment. Serum albumin level, which can be easily measured preoperatively, is an inexpensive and widely available parameter. Although there are studies in the literature demonstrating the prognostic significance of serum albumin levels and metastatic lymph node ratio in patients undergoing surgery for colorectal cancer, there is no study evaluating these two factors together. The aim of this study is to investigate the combined effect of serum albumin level and metastatic lymph node ratio on mortality and overall survival in patients with colorectal cancer. Material and Methods: Patients who underwent surgery for colorectal adenocarcinoma between 2012 and 2024 in our clinic were retrospectively reviewed using the hospital information system (HIS). The following data were collected: preoperative serum albumin levels, age, sex, tumor localization, histological type, T and N stages, tumor grade, tumor diameter, number of metastatic lymph nodes, total number of lymph nodes, presence of lymphovascular, vascular, and perineural invasion, survival status, and follow-up duration. The normal reference range for serum albumin in our institution is 3.5–5.5 mg/dL. In previous prognostic studies, the ratio of metastatic to total lymph nodes (MLNR) has been reported to range between 0.12 and 0.3. In our study, the cut-off value for MLNR was determined as 10%, and values above this threshold were considered to be associated with poor prognosis. In patients with colorectal adenocarcinoma, serum albumin level and metastatic lymph node ratio were compared in terms of survival, follow-up duration, and mortality rates. Mortality rates were compared based on the combined criterion of albumin < 3.5 mg/dL and MLNR > 10%. According to serum albumin levels, patients with albumin < 3.5 mg/dL and those with ≥ 3.5 mg/dL were evaluated in terms of survival and mortality. Similarly, according to the metastatic to-total lymph node ratio, patients with MLNR ≤ 10% and > 10% were analyzed regarding survival and mortality outcomes. xvii Results: The combination of albumin < 3.5 mg/dL and a metastatic-to-total lymph node ratio (MLNR) > 10% demonstrated a significant discriminative ability in distinguishing deceased and surviving patients [area under the curve (AUC): 0.667 (0.624– 0.710)]. For this combined criterion, sensitivity was 34.3%, positive predictive value 96.0%, specificity 99.1%, and negative predictive value 70.2%. Serum albumin level alone also showed significant discriminative power in differentiating between patients with and without mortality [AUC: 0.846 (0.814–0.878)]. Using a cut-off value of 3.5 mg/dL, serum albumin demonstrated a strong predictive performance [AUC: 0.811 (0.775–0.847)], with a sensitivity of 69.3%, positive predictive value of 86.1%, specificity of 92.8%, and negative predictive value of 82.5%. The estimated mean survival time was significantly shorter in patients with albumin < 3.5 mg/dL (37.8 months) compared to those with albumin ≥ 3.5 mg/dL (139.5 months) (p < 0.05). Similarly, patients with MLNR > 10% had a significantly shorter mean survival time (39.7 months) than those with MLNR < 10% (128.0 months) (p < 0.05). The MLNR also demonstrated significant discriminative ability for mortality prediction [AUC: 0.730 (0.689– 0.771)]. Using a cut-off value of 10%, MLNR showed comparable predictive performance [AUC: 0.731 (0.690–0.771)], with a sensitivity of 53.1%, positive predictive value of 83.1%, specificity of 93.1%, and negative predictive value of 75.6%. Conclusion: It is well established that in colorectal cancer, an increase in patient age and tumor stage is associated with poorer prognosis, and our study confirmed this finding. We demonstrated that hypoalbuminemia negatively affects prognosis and increases mortality rates in patients with colorectal cancer. Therefore, maintaining serum albumin levels within or above the normal range appears to be important for favorable outcomes. Our study also showed that xviii a higher metastatic lymph node ratio adversely affects prognosis and is associated with increased mortality. The coexistence of hypoalbuminemia and an elevated metastatic lymph node ratio may be considered a strong indicator of poor prognosis in patients with colorectal cancer. Keywords: Colorectal cancers, hypoalbuminemia, metastatic lymph node, metastatic lymph node rate