Prognostic impact of inflammatory and nutritional markers in colorectal cancer patients with peritoneal metastasis

Abstract

In this article, we critically appraise the study by Wu et al, which investigated the prognostic value of preoperative inflammatory and nutritional markers in colorectal cancer patients with peritoneal metastasis. This retrospective cohort study included 133 patients. The findings indicate that patients with high neutrophil-to-lymphocyte ratios (NLRs) or lower hemoglobin (Hb) levels have significantly shorter overall survival (OS) than those with lower NLRs or normal Hb levels, respectively. Furthermore, age, carbohydrate antigen 199 levels, the NLR, Hb, and the peritoneal cancer index were identified as independent prognostic factors for OS. A nomogram was subsequently developed, demonstrating its ability to accurately predict the OS of colorectal cancer patients with peritoneal metastasis. This study introduces a potentially valuable prognostic tool for these patients. However, further validation in multicenter cohorts is needed to confirm its clinical applicability, to assess its limitations, and to elucidate the underlying mechanism of these identified biomarkers.

Key Words: Colorectal cancer; Peritoneal metastasis; Inflammatory markers; Nutritional markers; Prognosis

Core Tip: Colorectal cancer (CRC) remains a major global health challenge, with metastasis posing a critical obstacle to treatment and patient management. Preoperative inflammatory and nutritional markers have been identified as independent prognostic markers for CRC patients with peritoneal metastasis. When combined with age, carbohydrate antigen 199 levels, and the peritoneal cancer index, these markers provide a reliable method for predicting overall survival. This combination offers a promising tool for predicting the prognosis and guiding the treatment of CRC with peritoneal metastasis.

TO THE EDITOR

Colorectal cancer (CRC) is a major global health concern, ranking as the third most commonly diagnosed cancer in 2022, with an estimated 1.9 million new cases. It is also the second leading cause of cancer-related mortality, accounting for approximately 904000 deaths in the same year[1]. The global incidence of CRC is expected to increase to approximately 2.5 million cases by 2035; the increase is driven primarily by increasing rates in developing countries[2]. The pathogenesis of CRC is influenced by both genetic and environmental risk factors, with 10%-20% of cases related to familial predisposition[3,4]. The degree of risk is modulated by the number of affected relatives and the age at diagnosis[5]. Most CRC cases remain asymptomatic until they reach an advanced stage[3]. The prognosis of CRC depends on the degree of tumor invasion at diagnosis. Metastatic CRC, characterized by its spread to distant organs such as the liver, lungs, peritoneum, and lymph nodes, represents a critical challenge in its management. The presence of metastasis is strongly associated with advanced disease and markedly reduced survival[6]. Approximately 35% of CRC patients present with metastasis at initial diagnosis, and up to 50% of patients diagnosed with localized disease will eventually develop metastasis[7,8]. Identification of reliable preoperative biomarkers of metastasis is urgently needed to reduce the mortality rate of CRC patients.

EDITORIAL COMMENTARY

In this article, we review the study by Wu et al[9], which highlighted the prognostic significance of preoperative inflammatory and nutritional markers in CRC patients with peritoneal metastasis. These markers have emerged as crucial indicators of prognosis and clinical outcomes in CRC, with increasing evidence supporting the correlation between inflammation, nutritional status, and tumor progression[10]. Although carcinoembryonic antigen has been widely recommended as a valuable biomarker for CRC prediction in clinical guidelines, systemic inflammation and nutritional markers can provide additional prognostic value as complementary markers. Exacerbated inflammation supports formation of a protumorigenic microenvironment that promotes cancer cell proliferation, invasion, and angiogenesis, thus contributing to poorer patient outcomes[11]. Furthermore, preoperative compromised nutritional status is related to increased postoperative morbidity and mortality[12].

Several studies have investigated the associations between preoperative inflammatory markers and clinical outcomes in patients with CRC[13,14]. Inflammatory markers, such as C-reactive protein, the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio, are important indicators of systemic inflammation and play pivotal roles in tumor progression. Elevated levels of these markers are thought to reflect the inflammatory response that supports tumor growth and metastatic spread, possibly through mechanisms such as enhanced angiogenesis and immune evasion[13,14]. Moreover, these inflammatory markers have been linked to adverse clinical outcomes, including tumor recurrence and poor survival[15]. For example, the NLR, lymphocyte monocyte ratio (LMR), and platelet-to-lymphocyte ratio have all been identified as independent prognostic factors for CRC[15]. Scores that integrate inflammatory markers, such as the modified Glasgow prognostic score (mGPS), have been shown to facilitate accurate prognostic stratification. Park et al[16] demonstrated that the mGPS combined with the tumor-node-metastasis stage effectively stratifies CRC patients on the basis of outcomes, thereby optimizing clinical decision-making and resource allocation. Similarly, Suzuki et al[17] reported that the systemic inflammation score, which is based on the preoperative serum albumin level and lymphocyte-to-monocyte ratio, exhibits superior prognostic value over the Glasgow prognostic score in CRC patients undergoing curative resection. Furthermore, Golder et al[18] revealed that the preoperative systemic inflammatory response, measured through composite indices such as the mGPS and NLR, can be used to stratify colon cancer patients according to survival outcomes.

Nutritional markers, on the other hand, provide essential information about the nutritional status of the body. Nutritional status is intrinsically linked to immune competence, metabolic stability and overall health resilience. Nutritional markers are similarly critical in the preoperative assessment of CRC patients. Nutritional status directly impacts immune function, metabolic homeostasis, and the body’s ability to withstand surgical stress. A variety of nutritional markers, such as albumin, prealbumin, the prognostic nutritional index (PNI), controlling nutritional status score and the C-reactive protein-to-albumin ratio, have been proposed as important prognostic indicators for CRC. Malnutrition, as indicated by low levels of these markers, is associated with poorer treatment responses, increased incidence of postoperative complications, and shorter overall survival (OS)[19,20]. Preoperative nutritional status serves as a surrogate for physiological reserve, and impaired nutritional status has been shown to correlate with higher rates of postoperative morbidity and mortality[12,21]. For example, a study of a large cohort study of 992 patients with stage III colon cancer revealed that a healthy body mass index is associated with improved survival outcomes[22]. Serum albumin, which is often decreased in CRC patients, is widely recognized as a marker of malnutrition and a predictor of a poor prognosis[23]. Heys et al[24] first identified hypoalbuminemia as an independent prognostic factor in CRC, and subsequent studies have corroborated its predictive value. Additionally, Okuno et al[25] demonstrated that muscle mass depletion, assessed by radiological imaging, is a significant predictor of recurrence-free survival in CRC patients.

The combined assessment of nutritional and inflammatory status, typically through composite indices such as the mGPS and PNI, provides a more comprehensive approach to prognostic assessment[26]. These composite indices improve predictive accuracy by reflecting the effects of systemic inflammation and nutritional status, which are both critical in determining patient outcomes. Patients with elevated Glasgow prognostic scores or low PNI scores are at a significantly greater risk of adverse clinical outcomes, highlighting the importance of comprehensive approaches for preoperative assessment[26].

In the study conducted by Wu et al[9], 133 CRC patients with peritoneal metastasis were included. The results revealed that patients with a high NLR or low hemoglobin (Hb) level had significantly shorter OS than those with a lower NLR or normal Hb level. Multivariate analysis identified age, carbohydrate antigen 199 levels, the NLR, Hb, and the PCI as independent predictors of OS. A nomogram was developed to predict OS with high accuracy in this patient cohort. In this work, Wu et al[9] developed a nomogram in which the NLR and Hb level were used to estimate 1-year and 2-year survival probabilities, which was novel. The nomogram helped to predict short-term patient survival. This study provides a valuable prognostic tool for the clinical management of CRC with peritoneal metastasis. However, this study was conducted at a single center, and this nomogram has not been validated. Further validation in multicenter cohorts is necessary to assess the clinical utility of this tool, to explore its limitations, and to better understand the underlying mechanisms of these biomarkers.

CONCLUSION

In conclusion, preoperative inflammatory and nutritional markers can serve as vital prognostic indicators in CRC patients with peritoneal metastasis. These markers can provide valuable insights into disease progression and clinical outcomes. Future studies are needed to validate this prognostic tool in larger, multicenter cohorts and to explore the mechanism underlying the involvement of these markers in cancer progression, thereby clarifying their application value.