Colorectal cancer (CRC) is the third most diagnosed cancer worldwide and the second most common cause of cancer-related deaths, with a noticeable shift toward younger populations (1, 2). Significant advancements have been achieved in both the diagnosis and treatment of CRC. Currently, therapeutic strategies for both early and advanced colorectal cancer are based on a comprehensive approach that includes surgery, radiotherapy, chemotherapy, interventional methods, biotherapy, and photothermal therapy (3). Chemotherapy can be used as an adjuvant or neoadjuvant therapy, aiming to reduce recurrence and improve survival rates (4, 5). This is especially true for patients with stage III CRC (6). The long-term prognosis for CRC patients undergoing chemotherapy varies, influenced by factors such as tumor stage, molecular markers, and the patient’s immune status.

The platelet-to-lymphocyte ratio (PLR) is a novel inflammatory marker calculated by dividing the platelet count by the lymphocyte count (7). In recent years, numerous studies have indicated an association between PLR and the prognosis of CRC patients (6). For instance, An, S. H. et al. (8) examined the association between PLR and 5-year overall survival (OS), disease-free survival (DFS), and the pathological complete response (pCR) rate. Multivariate analysis identified pretreatment PLR as an independent predictor of overall survival (hazard ratio: 1.850; 95% CI: 1.041–3.287; p = 0.036). These findings suggest that pretreatment PLR may serve as a prognostic marker for OS in patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy followed by curative surgery. Sato et al. (9) showed that, in patients with pathological stage I to III CRC, preoperative PLR and pre-stenting PLR were associated with poorer RFS. PLR may reflect the inflammatory and immune status of CRC patients, and elevated PLR often indicates a pro-inflammatory state and immune dysfunction, which are unfavorable for tumor prognosis. Therefore, there is no definite conclusion on the exact prognostic value of PLR for CRC patients receiving chemotherapy.

Several meta-analyses have explored the association between PLR and CRC prognosis. A meta-analysis by Guo et al. (1) incorporated 27 studies encompassing a total of 13,330 patients. The results indicated that elevated PLR levels were significantly associated with poorer OS (HR = 1.40; 95% CI: 1.21–1.62; p < 0.00001), DFS (HR = 1.44; 95% CI: 1.09–1.90; p = 0.01), and relapse-free survival (RFS) (HR = 1.48; 95% CI: 1.13–1.94; p = 0.005). In contrast, no statistically significant associations were observed for progression-free survival (PFS) (HR = 1.14; 95% CI: 0.84–1.54; p = 0.40) or cancer-specific survival (CSS) (HR = 1.16; 95% CI: 0.88–1.53; p = 0.28). However, Guo et al. did not specifically focus on the association between PLR and prognosis in individuals diagnosed with CRC receiving chemotherapy. Furthermore, after their research was published, new studies yielded conclusions that are not entirely consistent (8, 10, 11). Therefore, the purpose of this meta-analysis was to synthesize this new evidence and specifically investigate the prognostic value of PLR in the distinct and clinically relevant population of CRC patients undergoing chemotherapy.

Inflammation plays a pivotal role as one of the primary contributors to colorectal carcinogenesis (28). Among various biomarkers, the PLR has shown potential in predicting survival outcomes in patients with CRC (29). Research by Hong-Xin Peng found that higher PLR levels correlate with poor OS, particularly in metastatic CRC patients of Caucasian descent. A meta-analysis including 12 studies with 3,541 patients further supported this association, revealing that a high PLR significantly affects OS, DFS, and CSS in both the overall population and the Caucasian subgroup. Interestingly, increased PLR was not correlated with DFS in individuals treated solely with surgery, but it was strongly linked to poorer survival outcomes in metastatic CRC patients. This suggests that PLR has prognostic relevance for OS, DFS, and PFS in the metastatic subgroup. While these findings underscore the potential of PLR as a prognostic biomarker, especially in metastatic Caucasian patients, further research is needed to validate these associations and confirm its clinical utility (30).

In recent years, inflammatory indicators such as PLR, NLR (31, 32), and LMR are of great significance in the diagnosis and prognosis of various cancers, including CRC (11, 33). The relationship between PLR and CRC prognosis, confirmed by a growing body of research, has therefore drawn considerable attention. In our study, we conducted a meta-analysis including 19 studies (26 comparative groups), encompassing a total of 4,422 patients, to assess the prognostic value of PLR in CRC survival. Unlike previous meta-analyses that examined PLR across all treatment modalities, our study specifically focused on patients receiving chemotherapy, allowing for a more tailored assessment of its prognostic utility in this subpopulation. Our results demonstrated a significant association between higher PLR and both OS and PFS. However, no statistically significant association was found between PLR and CSS. One possible explanation for the lack of significance regarding CSS is that these data were derived from different subgroups within the same studies. Additional high-quality research is warranted to further evaluate whether PLR can reliably predict CSS in CRC patients.

Sensitivity analysis revealed that PLR for predicting PFS in CRC patients undergoing chemotherapy was unstable. This suggests the need for further research to confirm the relationship between PLR and PFS. Nonetheless, evaluation of publication bias using Egger’s test and funnel plots indicated no significant risk of bias for the three outcomes-OS, PFS, and CSS-suggesting a relatively high level of evidence. Our meta-analysis demonstrated that higher PLR levels are significantly associated with worse OS (1). Interestingly, even though Ganlin Guo’s study did not stratify patients based on treatment modalities, PLR remained predictive of OS, indicating that the type of treatment may not significantly influence the prognostic value of PLR. Despite this, the association between PLR and PFS prediction is inconclusive. While Ganlin Guo concluded that PLR had no significant prognostic value for either PFS or CSS, our study found a significant correlation between elevated PLR and PFS, though not with CSS. A key difference between the two studies lies in the inclusion criteria: our study limited the analysis to patients undergoing chemotherapy, whereas Guo’s analysis did not. This specific focus on a treatment-defined population likely explains the divergent finding regarding PFS, suggesting that chemotherapy may modulate the relationship between PLR and disease progression. Furthermore, our meta-analysis incorporated several additional methodological approaches—such as subgroup analysis, sensitivity analysis, and publication bias assessment via funnel plots—to evaluate evidence quality more rigorously. These methods allowed us to explore the optimal application conditions and target populations for PLR, thereby improving the robustness of the research.

In our systematic review and meta-analysis, subgroup analyses revealed that PLR lacked prognostic significance in specific contexts: metastatic colorectal cancer, PLR cut-off values <150, populations from the United States, and patients treated with chemotherapy alone. Several epidemiological and clinical explanations may account for these observations. Firstly, in metastatic CRC, the disease has reached an advanced phase characterized by extensive pathological changes, a high tumor burden, and a compromised immune system. At this point, systemic inflammation and immune responses may be highly dysregulated or have reached a plateau. Consequently, PLR, which reflects the balance between platelets and lymphocytes, may no longer serve as a reliable indicator of prognosis. Some studies have shown that in advanced cancers, complex immunosuppressive mechanisms can obscure the predictive value of simple inflammatory markers such as PLR. Secondly, regarding the PLR cut-off value <150, the prognostic utility of PLR depends heavily on the threshold used to define high and low levels. Different studies adopt various methods to determine cut-off values-e.g., medians, receiver operating characteristic (ROC) curve analysis, or other statistical criteria. When a relatively low threshold such as <150 is used, it may not sufficiently differentiate high-risk patients, particularly in cohorts with generally lower PLR distributions. In such cases, the prognostic difference between high and low PLR groups may be negligible, leading to an apparent lack of significance. Indeed, some studies suggest that using higher cut-off values may improve the predictive performance of PLR in survival analysis.

Thirdly, regional differences-particularly in American populations-may also contribute to the observed variation in the prognostic value of PLR. Genetic, environmental, and lifestyle factors vary significantly across regions and can influence both the epidemiology of colorectal cancer and its associated biomarkers. In the American population, a high degree of genetic heterogeneity exists, alongside unique environmental exposures, dietary patterns, and disparities in healthcare access. These factors can collectively affect the host’s immune-inflammatory response, potentially altering the relationship between PLR and patient prognosis. Moreover, differences in clinical practice and treatment protocols across countries may further impact the prognostic utility of PLR. For example, American treatment guidelines for colorectal cancer-including chemotherapy regimens, the use of targeted therapies, and follow-up strategies-may differ from those used in Asian or European countries. These regional disparities may reduce the consistency of PLR’s prognostic value when applied across diverse populations.

“Fourth, the geographical distribution of the included studies is a significant limitation. The majority of studies were conducted in China, which may introduce regional bias and limit the generalizability of our findings to other ethnic and geographical populations, particularly those of African or European ancestry. The biological behavior of CRC, host inflammatory responses, and treatment protocols can vary across regions. Therefore, extrapolation of our results to a global context should be done with caution. Future multicenter studies involving more diverse populations are urgently needed to validate the universal prognostic value of PLR.

Lastly, regarding treatment modality-chemotherapy alone. Patients receiving only chemotherapy may generally be in advanced stages of the disease, where the tumor has already metastasized and lost the opportunity for surgical resection. In such cases, the tumor’s biological behavior and the body’s immune-inflammatory response may differ from those in early-stage patients. Chemotherapy drugs primarily target tumor cells but may also suppress the immune system to some extent. This could further complicate the relationship between PLR and prognosis. In contrast, early-stage colorectal cancer patients with relatively intact immune function may exhibit a clearer association between PLR and prognosis. Some studies have also noted that the combination of chemotherapy and other treatments, such as targeted therapy, may alter the prognostic significance of PLR. In clinical practice, the following recommendations can be made based on these findings: when using PLR to assess the prognosis of colorectal cancer patients, it is advisable to select a PLR cut-off value of ≥150 to enhance its predictive accuracy. For metastatic colorectal cancer patients or those undergoing chemotherapy alone, PLR should be interpreted with caution, as its prognostic value may be limited. Greater emphasis should be placed on combining PLR with other clinical indicators and molecular markers to comprehensively evaluate prognosis. Furthermore, considering regional differences, treatment guidelines and practices for colorectal cancer should be developed and optimized based on local epidemiological characteristics. This will help improve the precision of prognosis prediction and provide more individualized treatment strategies. In conclusion, the prognostic value of PLR in individuals diagnosed with colorectal cancer is influenced by multiple factors, including disease stage, PLR cut-off value, geographic region, and treatment modality. Additional studies are needed to understand the mechanisms underlying these associations and to establish more appropriate PLR cut-off values and application scenarios for different populations. This will enable the effective use of PLR in clinical prognosis prediction.

Studies have shown the significance of the PLR as an indicator of the body’s inflammatory response, which is intricately connected to tumor development (34, 35). Inflammation, a fundamental component of the immune system, can create a favorable environment for cancer progression. Within the tumor microenvironment, a complex interplay of cellular interactions occurs, involving inflammatory cells and platelets that release a variety of substances contributing to cancer development (36, 37). Inflammatory cells secrete bioactive factors, such as cytokines and chemokines, which modulate the immune response and contribute to the creation of a pro-tumorigenic environment. These factors are essential for initiating and sustaining the inflammatory processes that support tumor growth. Platelets, in turn, release several key substances, including adhesion molecules that facilitate cancer cell attachment to the extracellular matrix, angiogenic factors that stimulate the formation of new blood vessels to nourish the growing tumor, and tumor-promoting factors that enhance cancer cell survival and proliferation (38, 39). Collectively, these substances drive tumor formation, angiogenesis, cancer cell invasion, metastasis, and overall tumor progression (40, 41). In the context of colorectal cancer-a common malignancy associated with significant morbidity and mortality-PLR levels have been shown to increase progressively as the disease advances (1). Elevated PLR values correlate with poorer prognosis, indicating that PLR may be a useful prognostic marker. Monitoring PLR levels can provide clinicians with a simple and non-invasive tool to assess disease progression and guide treatment decisions. This biomarker offers a potential means to identify patients at higher risk of poor outcomes, enabling earlier interventions and potentially improving survival rates. Further research into the mechanisms underlying the association between PLR and cancer progression may facilitate the development of new therapeutic strategies targeting inflammation and tumor microenvironment interactions.

Our results provide a more accurate reflection of the association between PLR and CRC prognosis. However, several limitations of our study should be acknowledged. First, much of the data comes from China, and thus the risk of selection bias cannot be eliminated. Second, the sample size was relatively small, which limits the generalizability of our results. We acknowledge that our research is not without flaws; nevertheless, it offers clinically relevant insights into the prognostic value of PLR in colorectal cancer. We look forward to future high-quality, multicenter RCTs to minimize these biases and further validate our findings.

We employed the term ‘colorectal cancer (CRC)’ to reflect the broader patient population encompassed by the included studies, many of which grouped colon and rectal cancers together. We acknowledge the distinct anatomical and clinical characteristics between colon and rectal cancer, which may influence outcomes. The prognostic value of PLR might differ between these two sub-types based on their specific tumor microenvironments and treatment paradigms (e.g., the central role of neoadjuvant chemoradiation in rectal cancer). Unfortunately, the primary studies did not provide sufficient disaggregated data to perform a subgroup analysis based on the primary tumor site. This represents a limitation of our analysis and highlights an important area for future research. Future prospective studies should aim to investigate the prognostic role of PLR in colon cancer and rectal cancer cohorts separately.

Our meta-analysis revealed that PLR is a significant predictor of OS and PFS in CRC patients undergoing chemotherapy. Specifically, higher PLR values were associated with shorter survival times in this patient group. Further subgroup analyses indicated that several factors-including population characteristics, PLR cut-off values, geographic region, treatment methods, patient age, and sample size-may influence the predictive efficacy of PLR in this context.

However, it should be emphasized that most of the studies included were retrospective in nature, had relatively small sample sizes, and may have limitations regarding result stability. Therefore, we recommend that future research focus on prospective, multicenter studies to further validate the prognostic value of PLR in CRC patients receiving chemotherapy. Such studies will help provide more robust and reliable evidence to support the clinical application of PLR as a prognostic biomarker in this patient population.