Table of Contents
Introduction
Colorectal cancer (CRC) has become a significant public health concern, as evidenced by GLOBOCAN 2020 data indicating it as the third most prevalent cancer worldwide. Approximately half of CRC patients are diagnosed with metastatic disease, and colon cancer accounts for the majority of these cases. Current prognostic assessments largely depend on the tumor stage and histopathological characteristics according to the American Joint Committee on Cancer (AJCC) TNM staging system. However, patients with identical tumor stages can experience widely varying clinical outcomes, underscoring the necessity for additional prognostic indicators that can refine treatment strategies and improve survival rates.
Recent studies have illuminated the role of cancer-related inflammation in tumor development and progression. Specifically, peripheral blood markers such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have emerged as potential prognostic tools across various malignancies, including CRC. This article will delve into the importance of these ratios, the implications of tumor stage and nodal involvement, as well as the overall impact of inflammation on CRC prognosis. Furthermore, we will explore future directions for research in identifying reliable prognostic indicators for colorectal cancer.
Importance of Neutrophil-Lymphocyte Ratio in Cancer Prognosis
The neutrophil-to-lymphocyte ratio (NLR) is a significant marker that reflects systemic inflammation, which has been shown to correlate with cancer prognosis. Elevated NLR levels have been associated with poor outcomes in various cancer types, including CRC. A systematic review and meta-analysis have confirmed that an increased NLR correlates with decreased overall survival (OS) in CRC patients, making it a vital prognostic indicator.
In a study conducted on 349 CRC patients, a high preoperative NLR (≥2.61) was observed in nearly half of the cohort, which correlated significantly with tumor stage and other clinical parameters. Interestingly, while pre-NLR has been associated with worse outcomes, the postoperative NLR’s prognostic significance remains less clear. Some studies suggest that an elevated postoperative NLR does not significantly impact OS or relapse-free survival (RFS) rates, indicating a need for further research to clarify these relationships.
Table 1: Clinical Characteristics of CRC Patients by NLR Levels
| Parameter | Pre-NLR < 2.61 | Pre-NLR ≥ 2.61 | P-value |
|---|---|---|---|
| Age < 60 years | 54.8% | 45.2% | 0.256 |
| Male Gender | 52.0% | 48.0% | 0.421 |
| Node Status (Negative) | 50.0% | 50.0% | 0.952 |
| Clinical Stage I | 63.3% | 36.7% | 0.012* |
| Clinical Stage II | 46.8% | 53.2% | 0.470 |
| Clinical Stage III | 53.7% | 46.3% | 0.360 |
| Clinical Stage IV | 25.9% | 74.1% | 0.001* |
The clinical characteristics outlined in Table 1 indicate that specific demographic factors, such as age and gender, interact with NLR levels to influence prognosis. For example, patients aged 60 years or older tend to present with higher NLR levels, which may suggest a more aggressive disease course or a greater inflammatory response.
Role of Platelet-Lymphocyte Ratio in Colorectal Cancer Outcomes
Similar to NLR, the platelet-to-lymphocyte ratio (PLR) serves as another inflammatory marker that has gained attention in cancer prognosis. Elevated PLR levels indicate a heightened inflammatory state, which can contribute to tumor progression and poorer outcomes. Studies have shown that a high PLR correlates with worse survival rates in CRC patients, further emphasizing its utility as a prognostic marker.
In the cohort of 349 CRC patients, a significant proportion exhibited high preoperative PLR levels (≥145.38). Interestingly, the postoperative PLR levels showed a trend towards association with OS and RFS, suggesting that PLR may have additional prognostic value when considered alongside NLR.
Table 2: Clinical Characteristics of CRC Patients by PLR Levels
| Parameter | Pre-PLR < 145.38 | Pre-PLR ≥ 145.38 | P-value |
|---|---|---|---|
| Age < 60 years | 52.9% | 47.1% | 0.505 |
| Male Gender | 56.4% | 43.6% | 0.006* |
| Node Status (Negative) | 50.0% | 50.0% | 0.952 |
| Clinical Stage I | 67.3% | 32.7% | 0.003* |
| Clinical Stage II | 45.3% | 54.7% | 0.470 |
| Clinical Stage III | 53.7% | 46.3% | 0.360 |
| Clinical Stage IV | 25.9% | 74.1% | 0.001* |
The findings in Table 2 illustrate that elevated pre-PLR levels are linked to more advanced clinical stages of CRC. This indicates that PLR may serve as a useful biomarker to evaluate disease severity and tailor treatment strategies accordingly.
Significance of Tumor Stage and Node Status in Survival Rates
The tumor stage and node status remain the cornerstones of prognostic assessment in CRC. According to the AJCC TNM staging system, the extent of tumor invasion (T stage) and the presence of lymph node metastases (N status) are critical factors influencing survival outcomes.
In our study, multivariate analysis revealed that both T stage and node status were independent prognostic indicators for OS and RFS in CRC patients. Specifically, patients with node-negative disease had a significantly better prognosis compared to those with node-positive disease. Additionally, early-stage patients (Stage I and II) demonstrated higher survival rates compared to those diagnosed at more advanced stages (Stage III and IV).
Table 3: Univariate and Multivariate Analysis of Prognostic Factors
| Prognostic Factor | Univariate HR (95% CI) | P-value | Multivariate HR (95% CI) | P-value |
|---|---|---|---|---|
| Age (<60 vs ≥60) | 0.847 (0.479–1.496) | 0.577 | - | - |
| Gender (male vs female) | 1.122 (0.648–1.942) | 0.683 | - | - |
| Node Status (negative vs positive) | 0.387 (0.215–0.649) | <0.001* | 0.382 (0.184–0.751) | 0.006* |
| Clinical Stage (I vs IV) | 0.216 (0.113–0.415) | <0.001* | 0.235 (0.138–0.401) | <0.001* |
The data presented in Table 3 underscores the continued relevance of tumor staging and node involvement in predicting patient outcomes. These factors remain entrenched in routine clinical practice and are essential for informing treatment decisions.
Analyzing the Impact of Inflammation on Cancer Progression
The interplay between inflammation and cancer progression is a burgeoning area of research, particularly in the context of CRC. Chronic inflammation has been implicated in promoting tumorigenesis and metastasis, with inflammatory cells such as neutrophils and lymphocytes playing pivotal roles in this process.
Neutrophils, often associated with tumor-promoting inflammation, can facilitate tumor growth and metastasis by producing pro-inflammatory cytokines and promoting angiogenesis. Conversely, lymphocytes are generally considered to have an antitumor effect, capable of inducing apoptosis in malignant cells. The balance between these two immune cell types, as reflected in NLR and PLR, may provide insights into the underlying mechanisms of tumor biology and patient prognosis.
Future Directions for Research on Cancer Prognostic Indicators
The evolving landscape of cancer research points towards the need for large-scale, multicenter studies to validate the prognostic utility of NLR and PLR in CRC. While preliminary findings suggest that these markers hold promise, inconsistencies in optimal cut-off values and the effects of post-surgical changes necessitate further investigation. Future research should focus on standardized methodologies for measuring NLR and PLR, as well as elucidating their potential roles in guiding therapeutic decisions.
Furthermore, integrating NLR and PLR with other biomarkers and clinical parameters may yield more accurate prognostic models. This could pave the way for personalized treatment approaches that enhance patient outcomes in CRC.
FAQ
What is the significance of NLR and PLR in colorectal cancer?
NLR and PLR serve as markers of systemic inflammation and have been associated with poor prognosis in CRC patients, reflecting tumor biology and immune response.
How do tumor stage and node status impact survival rates in CRC?
Higher tumor stages and positive node status are linked to decreased overall survival and relapse-free survival, making them critical factors in prognostic assessments.
Are there standard cut-off values for NLR and PLR in CRC?
Currently, there are no universally accepted cut-off values for NLR and PLR in CRC, and these values may differ across studies. Further research is needed to establish standardized criteri
What future research directions are suggested for CRC prognostic indicators?
Future research should focus on multicenter studies to validate findings, explore the interplay between inflammatory markers and tumor biology, and integrate these markers with existing clinical prognostic models.
References
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Preoperative and Postoperative Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio Measured From the Peripheral Blood of Patients with Colorectal Cancer. https://doi.org/10.2147/CMAR.S504532
2 -
Prognostic value of the neutrophil‑to‑lymphocyte ratio in renal cell carcinoma: A systematic review and meta‑analysis. https://pubmed.ncbi.nlm.nih.gov/11925002/
-
Renal parenchymal volume analysis: Clinical and research applications. https://pubmed.ncbi.nlm.nih.gov/11922601/
-
Primary Ewing sarcoma of renal origin with tumor thrombus into inferior vena cava: a case report. https://doi.org/10.1186/s13256-025-05157-7
