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Neutrophil-to-lymphocyte ratio as a prognostic factor in patients with castration-resistant prostate cancer treated with docetaxel-based chemotherapy: a meta-analysis

BMC Urology volume 25, Article number: 17 (2025) Cite this article

Abstract

Background

In recent years, many studies have illustrated that the neutrophil-to-lymphocyte ratio (NLR) is a prognostic factor of metastatic castration-resistant prostate cancer (mCRPC), but their conclusions are controversial. The aim of this study was to assess the prognostic value of the NLR in patients with mCRPC treated with docetaxel-based chemotherapy.

Methods

Database searches were conducted in PubMed, EMBASE and the Cochrane Library to retrieve relevant published English-language literature up to 20 February 2023. RevMan 5.4.1 was used to summarize the hazard ratio (HR) and its 95% confidence interval (CI) for overall survival (OS) and progression-free survival (PFS) with subgroup analysis. Finally, Stata software was adopted for sensitivity analysis, and Egger’s test was used to calculate the results of stability to determine whether there was publication bias.

Results

A total of 1,983 mCRPC patients from 14 retrospective cohort studies were included in this meta-analysis. The combined results showed that elevated NLR was significantly associated with worse OS (HR = 1.86, 95% CI: 1.55–2.23, P < 0.00001) and PFS (HR = 1.96 (95% CI: 1.52–2.53), P < 0.00001) in patients with mCRPC treated with docetaxel-based therapy. For subgroup analysis of high NLR, studies performed in Asia and cutoff value > 3 were associated with poorer OS, while cutoff values > 3 were associated with poorer PFS.

Conclusion

Our results suggest that the neutrophil-to-lymphocyte ratio may be a prognostic factor in patients with mCPRC with docetaxel-based chemotherapy.

Peer Review reports

Introduction

According to the World Health Organization (WHO) 2021 GLOBOCAN statistics, prostate cancer is the second most common cancer and the fifth leading cause of cancer death in men, and the incidence is on the rise [1]. Prostate cancer accounts for 29% of all cancer cases in men in 2023 and is the most common malignant tumor in men in 2023, with the second highest new case fatality rate after lung cancer [2].

Patients with advanced prostate cancer will almost always progress to mCRPC after a median time of 18–24 months of endocrine primary therapy, and patients will face disease progression, reduced quality of life, and shorter survival [3]. In this regard, other therapeutic interventions are needed.

Chemotherapy serves an important role for patients with mCRPC, and docetaxel is the first-line agent in chemotherapy [4]. The results of the SWOG-9916 and TAX-327 studies showed that treatment with docetaxel significantly prolonged median survival. At the same time, patients experienced significant pain relief, improved quality of life, and a significant increase in PSA remission rate [5]. Therefore, docetaxel combined with prednisone has become the standard of care for the treatment of patients with mCRPC [6, 7]. However, there is an urgent need for reliable, easily-measured and inexpensive predictive biomarkers to assess the prognosis of patients treated with docetaxel chemotherapy.

There is growing evidence that the systemic inflammatory response plays an important role in all stages of cancer [8]. It has been illustrated that inflammatory indicators have prognostic value for patients with mCRPC under docetaxel treatment [9,10,11], and the neutrophil-to-lymphocyte ratio is a common inflammatory indicator with the advantages of low cost and rapid detection which has been shown to be associated with the prognosis of a variety of malignancies [12], but the prediction of prognosis in patients with mCRPC treated with docetaxel is somewhat controversial [13, 14]. Therefore, the present meta-analysis aims to assess the value of the NLR in predicting the prognosis of patients with mCRPC treated with docetaxel.

Materials and methods

Search strategy and selection criteria

This study was conducted according to the guidelines of the Preferred Reporting in Systematic Reviews and Meta-Analyses (PRISMA) project [15]. We searched the PubMed, EMBASE and Cochrane Library electronic databases for articles. All studies published before February 20, 2023 were searched in languages restricted to English, without any national or article type restrictions. All selected articles were independently screened to avoid missing additional studies in the initial search. The following keywords and medical subject headings were used as search terms: (“metastatic castration-resistant prostate cancer”, or “mCRPC”) and (“neutrophil-to-lymphocyte ratio”, or “NLR”) and (“docetaxel”). The references were screened manually. Ultimately, we selected 14 records according to the flow chart in Fig. 1 [10, 16,17,18,19,20,21,22,23,24,25,26,27,28].

Fig. 1
figure 1

The flow chart according to the PRISMA statement

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Two authors (YZ and XZ) independently searched and selected these studies. Any differences were resolved by discussion until consensus was reached. Inclusion criteria were: [1] patients with a confirmed diagnosis of mCRPC; [2] patients receiving regular docetaxel treatment without other pharmacological interventions except ADT treatment; and [3] cohort studies assessing the prognostic value of pretreatment NLR, overall survival (OS) and progression-free survival (PFS) based on hazard ratios (HRs) and 95% confidence intervals (CIs). OS was defined as the time from initiation of treatment with docetaxel to death from any cause. PFS was defined as the time from initiation of docetaxel administration to disease progression or death from any cause or the last tumor evaluation. Duplicate studies, reviews, case reports, commentaries, letters, unpublished studies, conference abstracts, animal studies, incomplete or incorrect data, and studies for which HR values could not be extracted were excluded. Imaging and prostate-specific antigen (PSA) for PFS were also excluded.

Data extraction and quality evaluation

Both authors (YZ and XZ) independently extracted the data and resolved ambiguities through discussion. Data extraction included the following: authors, year of publication, study design, data source, mean age, outcome indicators, nation in which the study was conducted, duration, number of people included in the study, treatment modality, NLR cutoff value, and median follow-up time. The quality of the studies was then evaluated using the Newcastle‒Ottawa Scale (NOS), with a score of 5 being considered low quality, 6 to 7 being moderate quality, and 8 to 9 being high quality. Finally, all results were summarized in a patient characteristics table. The survival data related to Kaplan‒Meier curves were digitally extracted using Engauge Digitizer software.

Statistical analysis

HRs with 95% CIs were combined using RevMan 5.4.1 to assess survival values. The I2 statistic was used to evaluate the heterogeneity of the studies. I2 < 50% and p > 0.1 indicated nonsignificant heterogeneity, and a fixed-effects model was used. I2 > 50% and p < 0.1 indicated significant heterogeneity, and a random-effects model was used. Subgroup analyses were performed to determine the results of the meta-analysis and to identify the sources of heterogeneity. We conducted subgroup analyses on OS by country, publication date, sample size, and NLR cutoff value, and similarly, we performed subgroup analyses on PFS by publication date, sample size, and NLR cutoff value. We performed sensitivity analyses using Stata MP 17.0 to assess the stability of the results. We then assessed publication bias using Stata MP 17.0 Egger’s test, and funnel plots were used to assess the risk of bias using the Cochrane bias risk assessment tool. Finally, we used the trim and fill method to assess the impact of the bias on the result. The protocol for this systematic review was registered with INPLASY (INPLASY202330018) and is available in full from inplasy.com (https://inplasy.com/inplasy-2023-3-0018/).

Results

Included studies

The flowchart (Fig. 1) illustrates the process of literature selection. The initial search retrieved a total of 145 studies with potential for inclusion. Twenty-nine duplicate studies and 55 other types of studies (including case reports, reviews, letters, unpublished studies, conference abstracts, animal studies, etc.) remained after the exclusion of 61 studies. A further 8 studies for which the full text was not available were excluded. After reading the full text, 4 studies for which data were not available and 35 studies for nondocetaxel treatments were excluded. Ultimately, 14 studies were eligible and included in the qualitative synthesis [10, 16,17,18,19,20,21,22,23,24,25,26,27,28]. All included studies were retrospective cohort studies written in English.

Characteristics of the included studies

Table 1 summarizes the general characteristics of the 14 eligible cohort studies [10, 16,17,18,19,20,21,22,23,24,25,26,27,28]. A total of 1,983 mCRPC patients with mean age of 43–91 years were included in this meta-analysis. The sample size ranged from 41 to 357 cases. The years of publication were 2013–2022, the duration was 1998–2019, and the median follow-up was 1-118 months. The overall quality of the included studies was good, with NOS scores ranging from 6 to 8 (Table 1). Seven were Asian [19, 21, 22, 24,25,26,27], and seven were non-Asian [10, 16,17,18, 20, 23, 28]. Fourteen studies assessed the NLR [10, 16,17,18,19,20,21,22,23,24,25,26,27,28] with cutoff values of 1.8-5. Fourteen studies reported OS, and 5 studies reported PFS [16, 19,20,21, 26]. All 14 studies provided multifactorial analyses.

Table 1 Characteristics of the included studies
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The prognostic value of the NLR for OS

General overview: Forest plots (Fig. 2) show the combined results. Fourteen studies showed that elevated NLR was significantly associated with poorer OS in mCRPC patients receiving docetaxel (HR = 1.86, 95% CI: 1.55–2.23, P < 0.00001), with heterogeneity (I2 = 46%, heterogeneity = 0.03), so a random effects model was used for analysis [10, 16,17,18,19,20,21,22,23,24,25,26,27,28].

Fig. 2
figure 2

Pooled result for OS

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Subgroup analysis: To determine the source of heterogeneity, we performed a subgroup analysis of the nation where the study was conducted, time of publication, sample size and NLR cutoff value(Table 2). The results showed that elevated NLR in studies performed in Asia predicted lower OS (HR = 2.45, 95% CI: 1.93–3.13, P = < 0.00001)(Supplementary Fig. S1A). In subgroup analysis stratified by sample size, the number of included patients < 150 was associated with OS (HR = 2.11, 95% CI: 1.64–2.72, P < 0.00001)(Supplementary Fig. S1B). Cutoff values > 3 were associated with low OS (HR = 1.97, 95% CI: 1.15–3.39, P = 0.01)(Supplementary Fig. S1C). Studies published in 2021–2022 were associated with low OS (HR = 2.14, 95% CI: 1.59–2.88, P < 0.00001)(Supplementary Fig. S1D).

Table 2 Subgroups for OS analysis
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The prognostic value of the NLR for PFS

General overview

The forest plot (Fig. 3) shows the results after the combination. For progression-free survival (PFS), we evaluated 5 studies including 481 patients with RCC. A fixed-effects model (I2 = 0%, P = 0.92) was used because of low heterogeneity. Ultimately, we found that the higher the NLR was, the lower the PFS (HR = 1.96 (95% CI: 1.52–2.53), P < 0.00001) [19,20,21, 26, 27].

Fig. 3
figure 3

Pooled result for PFS

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Subgroup analysis

We also performed a subgroup analysis of PFS in mCRPC patients (Table 3). In the subgroup analysis stratified by year of publication, studies from 2021 to 2022 were associated with PFS (HR = 2.10, 95% CI: 1.45–3.30, P < 0.0001)(Supplementary Fig. S2A). The number of patients with mCRPC < 100 in the included studies was associated with PFS (HR = 2.15, 95% CI: 1.54–2.99, P < 0.00001)(Supplementary Fig. S2B). Studies with cutoff values > 3 were associated with poorer PFS (HR = 1.99, 95% CI: 1.30–3.06, P = 0.002)(Supplementary Fig. S2C).

Table 3 Subgroups for PFS analysis
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Sensitivity analysis and publication bias

Sensitivity analyses were performed on a study-by-study exclusion basis and showed no significant changes in the pooled HRs for OS and PFS, indicating the stability of the results (Fig. 4a, b). Publication bias was assessed by funnel plot and Egger’s test. When P < 0.05, the study was considered to have significant publication bias. The results showed publication bias in the study with combined OS (p = 0.000) and no publication bias in the study with combined PFS (p = 0.095) (Fig. 4c, d). Therefore, we analyzed the studies of OS using the trim and fill method, and the results showed that the presence of publication bias did not affect the stability of the results. The results of the Cochrane bias risk assessment tool showed that all studies had a high risk of bias in all 4 domains (Figs. 5 and 6).

Fig. 4
figure 4

Sensitivity analysis and Egger’s test for OS and PFS. a, c OS. b, d PFS

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Fig. 5
figure 5

Risk of bias graph

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Fig. 6
figure 6

Risk of bias summary

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Discussion

Prostate cancer is the second most common cancer and the fifth leading cause of cancer death in men, and its incidence is on the rise. In 2023, prostate cancer accounts for the most new cases of cancer in men and is the most common malignancy in men, with the second highest new case fatality rate after lung cancer [1, 2].

With the advent of new drugs such as enzalutamide, abiraterone, sipuleucel-T, cabazitaxel and radium 223, a variety of treatment options with good efficacy are available for patients with mCRPC [29]. There is currently a meta-analysis on the prognostic relationship between neutrophil-to-lymphocyte ratio (NLR) and outcomes in mCRPC patients treated with enzalutamide and abiraterone. The study results indicate that elevated NLR is significantly associated with poorer overall survival (OS). However, elevated NLR does not show significant correlation with adverse progression-free survival (PFS) in patients treated with abiraterone and enzalutamide [30]. However, docetaxel treatment still plays an important role as the standard of care in the treatment of patients with mCRPC [4]. Other taxane chemotherapy, including cabazitaxel are used as treatment options after failure of docetaxel therapy, more studies are still needed to demonstrate the prognostic value of NLR in other taxane chemotherapy [31]. The results of the SWOG 9916 and TAX 327 trials showed that docetaxel-based chemotherapy yielded a significant survival benefit of 20–24% over mitoxantrone in patients with mCRPC [5], but there is a lack of appropriate biomarkers to assess the efficacy of docetaxel treatment in patients with mCRPC. Therefore, the relationship between inflammation and tumor action has become more important [9,10,11]. The NLR is one of these inflammatory indicators and offers the advantages of ease of measurement and low cost. Although NLR has been shown to offer predictive value in the prognosis of many tumors [12], there is controversy regarding the prognostic value for patients with CPRC treated with docetaxel-based chemotherapy [13, 14]: there is no previous meta-analysis, and further evaluation is necessary. The study by Sümbül AT et al. [13] indicated no association between NLR and OS or PFS, but did not provide p-values or HR values. On the other hand, the study by Koo KC et al. [14] showed associations between NLR and OS, PFS, and CSS; however, due to incomplete data, these two studies were excluded.Therefore, this study conducted a systematic review and meta-analysis to assess the predictive value of the NLR in docetaxel-treated mCRPC patients to provide valuable information and optimize options for clinicians and patients.

A total of 14 studies with 1,983 patients were included in this meta-analysis, and the pooled results showed that a castration-resistant prostate cancer higher NLR was associated with worse OS and PFS, suggesting that this NLR is associated with prognosis in patients with CPRC treated with docetaxel-based therapy. Most of the studies included in this meta-analysis were conducted in Asia, so a subgroup analysis of the study region was performed. In addition, we chose 3 as the cutoff value because more studies chose 3 as the cutoff value, and using 3 as the cutoff value could better balance the number of two groups, Moreover, the heterogeneity was relatively low, and an NLR cutoff value of 3 also represents the median cutoff value used in all the included studies. And there has been a meta-analysis on the prognostic relationship between neutrophil-to-lymphocyte ratio (NLR) and outcomes in mCRPC patients treated with enzalutamide and abiraterone, which also selected an NLR cutoff value of 3 [30]. Furthermore, some studies suggest that an NLR value greater than 3 may indicate a pathological condition in the body, such as cancer, inflammation, or infection [32]. Over time, and with the emergence of various new therapies, we believe that the study period could introduce potential bias. However, since not all studies specified the year of the research, we chose the publication year for subgroup analysis. After conducting a thorough heterogeneity analysis, we determined that the current range of years is more appropriate. After the heterogeneity analysis of the cutoff values for each sample size one by one, the cutoff value with less heterogeneity was selected as the subgroup analysis. Because not all studies stated the year in which the study was conducted, we selected the year of publication for the subgroup analysis, and after performing heterogeneity analysis one by one, we decided that the current range of years was more appropriate. The results of the combined OS showed that in mCRPC patients of studies performed in Asia, an elevated NLR was more specific for predicting poorer prognosis than in studies performed in other region. NLR cutoff values > 3 had more significant prognostic values than cutoff values ≤ 3, suggesting that higher NLR cutoff values predicted poorer prognosis in docetaxel-treated mCRPC patients, whereas in patients with cutoff values ≤ 3, elevated NLR appeared to be a stronger predictor. Because of the heterogeneity in OS outcomes, we also performed subgroup analyses for year of publication and number of patients included in the study, The results showed that subgroups from 2021 to 2022 and subgroups with sample sizes less than 150 were associated with poorer overall survival (OS), suggesting a possible correlation with different healthcare standards across years. Variations in sample sizes among different studies may also influence the results. No significant heterogeneity was found when the Stangl-Kremser et al. [10] article was removed from the analysis of studies published in 2021–2022 or when the number of included studies was > 150. The effect on heterogeneity was greater when the Linton et al. [16] study was removed from studies published from 2013 to 2017. Therefore, these two studies may be the sources of heterogeneity, may be the number of studies included.The region, year of publication, and number of patients may be other factors. The heterogeneity in the study by Linton et al. may stem from differences in the populations across multiple countries, variations in methods of data collection, and the use of cutoff values different from most other studies. Additionally, it may be attributed to the prospective study compared to the retrospective study of others. Stangl-Kremser et al.‘s study heterogeneity may be due to regional differences in the populations included. Interestingly, there was no significant correlation between NLR in the Stangl-Kremser et al. [10] and Linton et al. [16] studies on the prognosis of mCRPC patients under docetaxel treatment, so the significance of NLR in prostate cancer patients merits further investigation. For the PFS results, we also combined the results and showed that studies with cutoff values > 3 had more significant prognostic values, showing an association with poorer prognosis. Although no significant heterogeneity was found, we still performed a subgroup analysis of the year of publication and the number of included studies, which also suggested no heterogeneity between the various subgroups. Finally, we conducted sensitivity analysis by systematically excluding studies one by one, and the results remained stable without significant impact.

In the past, a number of meta-analyses have also examined NLR-based prostate cancer prognosis, and their findings have indicated that elevated NLR suggests poorer OS and PFS in patients with mCRPC [33,34,35,36]. The study by Su et al. indicated that the NLR may be an independent prognostic predictor for 257 urological cancers [33]. However, NLR has not been evaluated in the context of predicting CPRC patients under docetaxel treatment. Some studies have illustrated that docetaxel has side effects of myelosuppression (mainly neutropenia) [37]. Therefore, based on these meta-analyses, our study linked the response of CPRC patients to docetaxel by focusing on NLR values. All studies that performed multifactorial analysis for NLR were included in this study because the results were more reliable when combining data from multifactorial analysis.

The systemic inflammatory response plays an important role in all stages of cancer [8], and the cells involved in inflammation include neutrophils, lymphocytes, monocytes and platelets. The neutrophil-to-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR) play important roles in the prognosis prediction of many tumors, including breast cancer [38], colorectal cancer [11], gastric cancer [39], laryngeal cancer [40], non-small cell lung cancer [41] and hepatocellular carcinoma [42]. Currently, docetaxel combined with prednisone has become the standard of care for treating patients with mCRPC [6, 7], and prednisone may lead to an increase in neutrophils while altering NLR values [43]. However, the mechanism of interaction between elevated NLR and poorer tumor prognosis is unclear. Neutrophils play an important role not only in promoting the secretion of a series of cytokines, such as IL-1β, IL-6, tumor necrosis factor or granulocyte colony-stimulating factor, but also in promoting angiogenesis and vascular endothelial growth and consequently stimulating tumor cell growth [44]. Conversely, lymphocytes play a crucial role in regulating immune antitumor activity, implying that a decrease in lymphocyte counts may indicate that tumor cells escape from the normal immune system, thus worsening the survival outcomes of cancer patients [45]. There are also differences in the impact of tumor burden on NLR. The degree of systemic inflammatory response differs between patients with oligometastatic and widespread metastatic prostate cancer [46]. The studies included in this meta-analysis all involved patients with bone, lymph node, and visceral metastases, but only the study by Philipp Nuhn and colleagues provided details on the number of metastatic lesions. Interestingly, we found discrepancies regarding visceral metastasis across different studies. In the research by Consuelo Buttigliero and Xin qi Pei, visceral metastasis was not associated with prognosis [20, 21], while in the studies by Judith Stangl-Kremser and Arnoud J. Templeton, it was associated with prognosis [10, 18]. Therefore, more research focusing on tumor burden is needed to confirm its impact on NLR. Overall, tumor progression is associated with an increase in neutrophil levels and a decrease in lymphocyte levels, which leads to increased NLR values. Therefore, the NLR can be useful as a monitor of cancer progression and treatment and provide useful information for changes in treatment decisions in CPRC patients. The present study supports pretreatment of NLR and other blood parameters to provide a valid assessment of host response for determining long-term survival.

It is important to note that the mCRPC patients included in the studies underwent treatments not only with docetaxel but also with other medications that could potentially influence NLR. In a study by D. Lorente and colleagues examining the relationship between corticosteroid use and NLR, although corticosteroid use was associated with an increase in NLR, overall, corticosteroid treatment did not alter the relationship between NLR and survival rate, suggesting that the prognostic value of NLR is independent of corticosteroid use [19]. The use of abiraterone may also affect NLR. In the research by Arnoud J. Templeton and colleagues, it was found that after excluding patients who received abiraterone before docetaxel treatment, the predictive model for NLR became more accurate(18). Hiroki Kobayashi and colleagues showed that the prognostic value of NLR differed between patients who had never received ARPI treatment and those who had, as abiraterone use could influence NLR [28]. Additionally, Leibowitz-Amit and colleagues reported that in mCRPC patients treated with abiraterone, lower baseline NLR was associated with OS [47]. While all the studies included in this meta-analysis involved androgen deprivation therapy, most did not specify the medications used, which may introduce some bias. Further research is needed to validate these findings.

The limitations of this study include the following: first, the small number of relevant studies and the small number of patients included did not allow for strong evidence in the analysis of some survival endpoints. Second, cancer-specific survival (CSS) and recurrence-free survival (RFS) are all important outcomes for survival analysis, but we were unable to analyze them due to the small amount of data. In addition, most of the studies we included were from Asia, Europe, and North America, and studies from other regions are still lacking and do not effectively represent all populations. Third, we searched the English literature and may have excluded studies with negative outcomes published in other languages. Fourth, the values of NLR in the included studies were not uniform, which may hinder clinical application, so more research evidence is needed to determine the optimal cutoff value. Moreover, NLRs are derived from peripheral blood and are susceptible to underlying patient conditions. Fifth, only retrospective cohort studies were included in this study, and there was some heterogeneity in the study treatments. Sixth, only docetaxel was mentioned in the studies included in this meta-analysis, and it was not stated whether NLRs in other taxane chemotherapy, including cabazitaxel, also have prognostic value. In addition, although the results obtained by trim and fill showed no effect of publication bias on the final results, some studies had low or moderate bias according to the NOS scale, and the presence of publication bias may be related to the small number of studies. Therefore, a wider range of studies and randomized controlled trials (RCTs) are needed to complement this in the future.

Conclusion

Overall, based on the evidence to date, the NLR is a reliable, inexpensive, and easily-identified predictive marker. Higher NLR is associated with poorer OS and PFS in mCRPC patients. The pretreatment of NLR may reflect the response of mCRPC patients to docetaxel and provide useful information for the treatment of mCRPC patients. However, due to the above limitations, more prospective high-quality studies are needed to determine the NLR to assess the prognosis of patients with mCRPC treated with docetaxel-based therapy.

Data availability

The authors confirm that the data supporting the findings of this study are available within the article.

References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer statistics 2020: GLOBOCAN estimates of incidence and Mortality Worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.

    Article  PubMed  Google Scholar 

  2. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17–48.

    Article  PubMed  Google Scholar 

  3. Friedlander TW, Ryan CJ. Targeting the androgen receptor. Urol Clin North Am. 2012;39(4):453–64.

    Article  PubMed  Google Scholar 

  4. Yap TA, Zivi A, Omlin A, de Bono JS. The changing therapeutic landscape of castration-resistant prostate cancer. Nat Rev Clin Oncol. 2011;8(10):597–610.

    Article  PubMed  CAS  Google Scholar 

  5. Berthold DR, Pond GR, Soban F, de Wit R, Eisenberger M, Tannock IF. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol. 2008;26(2):242–5.

    Article  PubMed  CAS  Google Scholar 

  6. Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502–12.

    Article  PubMed  CAS  Google Scholar 

  7. Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr., Jones JA, Taplin ME, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351(15):1513–20.

    Article  PubMed  CAS  Google Scholar 

  8. Greten FR, Grivennikov SI. Inflammation and Cancer: triggers, mechanisms, and consequences. Immunity. 2019;51(1):27–41.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Donate-Moreno MJ, Lorenzo-Sánchez MV, Díaz de Mera-Sánchez Migallón I, Herraiz-Raya L, Esper-Rueda JA, Legido-Gómez O, et al. Inflammatory markers as prognostic factors in metastatic castration-resistant prostate cancer. Actas Urol Esp (Engl Ed). 2020;44(10):692–700.

    Article  PubMed  CAS  Google Scholar 

  10. Stangl-Kremser J, Mari A, Suarez-Ibarrola R, D’Andrea D, Korn SM, Pones M, et al. Development of a prognostic model for survival time prediction in castration-resistant prostate cancer patients. Urol Oncol. 2020;38(6):600.e9-.e15

    Article  Google Scholar 

  11. Yamada Y, Sakamoto S, Rii J, Yamamoto S, Kamada S, Imamura Y, et al. Prognostic value of an inflammatory index for patients with metastatic castration-resistant prostate cancer. Prostate. 2020;80(7):559–69.

    Article  PubMed  CAS  Google Scholar 

  12. Ocana A, Nieto-Jiménez C, Pandiella A, Templeton AJ. Neutrophils in cancer: prognostic role and therapeutic strategies. Mol Cancer. 2017;16(1):137.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Sümbül AT, Sezer A, Abalı H, Köse F, Gültepe I, Mertsoylu H, et al. Neutrophil-to-lymphocyte ratio predicts PSA response, but not outcomes in patients with castration-resistant prostate cancer treated with docetaxel. Int Urol Nephrol. 2014;46(8):1531–5.

    Article  PubMed  Google Scholar 

  14. Koo KC, Lee JS, Ha JS, Han KS, Lee KS, Hah YS, et al. Optimal sequencing strategy using docetaxel and androgen receptor axis-targeted agents in patients with castration-resistant prostate cancer: utilization of neutrophil-to-lymphocyte ratio. World J Urol. 2019;37(11):2375–84.

    Article  PubMed  CAS  Google Scholar 

  15. Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015;350:g7647.

    Article  PubMed  Google Scholar 

  16. Linton A, Pond G, Clarke S, Vardy J, Galsky M, Sonpavde G. Glasgow prognostic score as a prognostic factor in metastatic castration-resistant prostate cancer treated with docetaxel-based chemotherapy. Clin Genitourin Cancer. 2013;11(4):423–30.

    Article  PubMed  Google Scholar 

  17. Nuhn P, Vaghasia AM, Goyal J, Zhou XC, Carducci MA, Eisenberger MA, et al. Association of pretreatment neutrophil-to-lymphocyte ratio (NLR) and overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line docetaxel. BJU Int. 2014;114(6):E11–7.

    PubMed  PubMed Central  CAS  Google Scholar 

  18. Templeton AJ, Pezaro C, Omlin A, McNamara MG, Leibowitz-Amit R, Vera-Badillo FE, et al. Simple prognostic score for metastatic castration-resistant prostate cancer with incorporation of neutrophil-to-lymphocyte ratio. Cancer. 2014;120(21):3346–52.

    Article  PubMed  CAS  Google Scholar 

  19. Yao A, Sejima T, Iwamoto H, Masago T, Morizane S, Honda M, et al. High neutrophil-to-lymphocyte ratio predicts poor clinical outcome in patients with castration-resistant prostate cancer treated with docetaxel chemotherapy. Int J Urol. 2015;22(9):827–33.

    Article  PubMed  CAS  Google Scholar 

  20. Buttigliero C, Pisano C, Tucci M, Vignani F, Bertaglia V, Iaconis D, et al. Prognostic impact of pretreatment neutrophil-to-lymphocyte ratio in castration-resistant prostate cancer patients treated with first-line docetaxel. Acta Oncol. 2017;56(4):555–62.

    Article  PubMed  CAS  Google Scholar 

  21. Pei XQ, He DL, Tian G, Lv W, Jiang YM, Wu DP, et al. Prognostic factors of first-line docetaxel treatment in castration-resistant prostate cancer: roles of neutrophil-to-lymphocyte ratio in patients from Northwestern China. Int Urol Nephrol. 2017;49(4):629–35.

    Article  PubMed  CAS  Google Scholar 

  22. Wu KJ, Pei XQ, Tian G, Wu DP, Fan JH, Jiang YM, et al. PSA time to nadir as a prognostic factor of first-line docetaxel treatment in castration-resistant prostate cancer: evidence from patients in Northwestern China. Asian J Androl. 2018;20(2):173–7.

    Article  PubMed  CAS  Google Scholar 

  23. Bello JO, Olanipekun OO, Babata AL. Prognostic value of neutrophil-to-lymphocyte ratio in castration resistant prostate cancer: single-centre study of Nigerian men. Niger J Clin Pract. 2019;22(4):511–5.

    Article  PubMed  CAS  Google Scholar 

  24. Man YN, Chen YF. Systemic immune-inflammation index, serum albumin, and fibrinogen impact prognosis in castration-resistant prostate cancer patients treated with first-line docetaxel. Int Urol Nephrol. 2019;51(12):2189–99.

    Article  PubMed  CAS  Google Scholar 

  25. Tatenuma T, Kawahara T, Hayashi N, Hasumi H, Makiyama K, Nakaigawa N et al. The Pretherapeutic Neutrophil-to-Lymphocyte Ratio for Docetaxel-Based Chemotherapy Is Useful for Predicting the Prognosis of Japanese Patients with Castration-Resistant Prostate Cancer. BioMed Research International. 2019;2019.

  26. Jiang ZG, Liao SG. Baseline neutrophil-lymphocyte ratio is associated with outcomes in patients with castration-resistant prostate cancer treated with Docetaxel in South China. Med (United States). 2021;100(39).

  27. Kobayashi H, Shiota M, Sato N, Kobayashi S, Matsumoto T, Monji K, et al. Differential prognostic impact of complete blood count-related parameters by prior use of novel androgen receptor pathway inhibitors in docetaxel-treated castration-resistant prostate cancer patients. Anti-cancer Drugsp. 2022;33(1):e541–7.

    Article  CAS  Google Scholar 

  28. Neuberger M, Goly N, Skladny J, Milczynski V, Weiß C, Wessels F et al. Systemic inflammatory biomarkers as predictive and prognostic factors in men with metastatic castration-refractory prostate cancer treated with docetaxel therapy: a comprehensive analysis in a German real-world cohort. J Cancer Res Clin Oncol. 2022.

  29. Cornford P, Bellmunt J, Bolla M, Briers E, De Santis M, Gross T, et al. EAU-ESTRO-SIOG guidelines on prostate Cancer. Part II: treatment of relapsing, metastatic, and castration-resistant prostate Cancer. Eur Urol. 2017;71(4):630–42.

    Article  PubMed  Google Scholar 

  30. Guan Y, Xiong H, Feng Y, Liao G, Tong T, Pang J. Revealing the prognostic landscape of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in metastatic castration-resistant prostate cancer patients treated with abiraterone or enzalutamide: a meta-analysis. Prostate Cancer Prostatic Dis. 2020;23(2):220–31.

    Article  PubMed  CAS  Google Scholar 

  31. Omlin A, Pezaro C, Gillessen Sommer S. Sequential use of novel therapeutics in advanced prostate cancer following docetaxel chemotherapy. Ther Adv Urol. 2014;6(1).

  32. Zahorec R. Neutrophil-to-lymphocyte ratio, past, present and future perspectives. Bratisl Lek Listy. 2021;122(7):474–88.

    PubMed  CAS  Google Scholar 

  33. Su S, Liu L, Li C, Zhang J, Li S. Prognostic role of pretreatment derived neutrophil to lymphocyte ratio in urological cancers: a systematic review and meta-analysis. Int J Surg. 2019;72:146–53.

    Article  PubMed  Google Scholar 

  34. Yin X, Xiao Y, Li F, Qi S, Yin Z, Gao J. Prognostic role of Neutrophil-to-lymphocyte ratio in prostate Cancer: a systematic review and Meta-analysis. Med (Baltim). 2016;95(3):e2544.

    Article  Google Scholar 

  35. Tang L, Li X, Wang B, Luo G, Gu L, Chen L, et al. Prognostic Value of Neutrophil-to-lymphocyte ratio in localized and advanced prostate Cancer: a systematic review and Meta-analysis. PLoS ONE. 2016;11(4):e0153981.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Gu X, Gao X, Li X, Qi X, Ma M, Qin S, et al. Prognostic significance of neutrophil-to-lymphocyte ratio in prostate cancer: evidence from 16,266 patients. Sci Rep. 2016;6:22089.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Markman M. Managing taxane toxicities. Support Care Cancer. 2003;11(3):144–7.

    Article  PubMed  Google Scholar 

  38. Graziano V, Grassadonia A, Iezzi L, Vici P, Pizzuti L, Barba M, et al. Combination of peripheral neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio is predictive of pathological complete response after neoadjuvant chemotherapy in breast cancer patients. Breast. 2019;44:33–8.

    Article  PubMed  Google Scholar 

  39. Hirahara T, Arigami T, Yanagita S, Matsushita D, Uchikado Y, Kita Y, et al. Combined neutrophil-lymphocyte ratio and platelet-lymphocyte ratio predicts chemotherapy response and prognosis in patients with advanced gastric cancer. BMC Cancer. 2019;19(1):672.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Woodley N, Rogers ADG, Turnbull K, Slim MAM, Ton T, Montgomery J, et al. Prognostic scores in laryngeal cancer. Eur Arch Otorhinolaryngol. 2022;279(7):3705–15.

    Article  PubMed  Google Scholar 

  41. Smith D, Raices M, Cayol F, Corvatta F, Caram L, Dietrich A. Is the neutrophil-to-lymphocyte ratio a prognostic factor in non-small cell lung cancer patients who receive adjuvant chemotherapy? Semin Oncol. 2022;49(6):482–9.

    Article  PubMed  CAS  Google Scholar 

  42. Yang T, Zhu J, Zhao L, Mai K, Ye J, Huang S, et al. Lymphocyte to monocyte ratio and neutrophil to lymphocyte ratio are superior inflammation-based predictors of recurrence in patients with hepatocellular carcinoma after hepatic resection. J Surg Oncol. 2017;115(6):718–28.

    Article  PubMed  CAS  Google Scholar 

  43. Dale DC, Fauci AS, Guerry DI, Wolff SM. Comparison of agents producing a neutrophilic leukocytosis in man. Hydrocortisone, prednisone, endotoxin, and etiocholanolone. J Clin Invest. 1975;56(4):808–13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Galdiero MR, Varricchi G, Loffredo S, Mantovani A, Marone G. Roles of neutrophils in cancer growth and progression. J Leukoc Biol. 2018;103(3):457–64.

    Article  PubMed  CAS  Google Scholar 

  45. Kishton RJ, Sukumar M, Restifo NP. Metabolic regulation of T cell longevity and function in Tumor Immunotherapy. Cell Metab. 2017;26(1):94–109.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Zaffaroni M, Vincini MG, Corrao G, Lorubbio C, Repetti I, Mastroleo F et al. Investigating Nutritional and Inflammatory Status as predictive biomarkers in oligoreccurent prostate Cancer-A RADIOSA Trial Preliminary Analysis. Nutrients. 2023;15(21).

  47. Leibowitz-Amit R, Templeton AJ, Omlin A, Pezaro C, Atenafu EG, Keizman D, et al. Clinical variables associated with PSA response to abiraterone acetate in patients with metastatic castration-resistant prostate cancer. Ann Oncol. 2014;25(3):657–62.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Funding

Research funding: This work was supported by the Project of Science and Technology Bureau of Xiamen (3502Z202373098), Natural Science Foundation of Fujian Province (2023J01121380 and 2024J011333).

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Authors and Affiliations

  1. The School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian Province, 350122, China

    Ying Zhang, Guangcheng Luo & Xinjun Wang

  2. Department of Urology, School of Medicine, Zhongshan Hospital of Xiamen University, Xiamen University, Xiamen, Fujian Province, 361004, China

    Xiao Zhou, Ran Xu, Guangcheng Luo & Xinjun Wang

  3. Department of Urology, Zhongshan Hospital Xiamen University, No.209 Hubin South Road, Siming District, Xiamen, Fujian Province, 361004, China

    Xinjun Wang

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Contributions

Ying Zhang and Xiao Zhou wrote the main manuscript text and Ran Xu and Xinjun Wang prepared Figs. 1, 2, 3, 4, 5 and 6 and Guangcheng Luo prepared Tables  1, 2 and 3. All authors reviewed the manuscript.

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Correspondence to Xinjun Wang.

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Zhang, Y., Zhou, X., Xu, R. et al. Neutrophil-to-lymphocyte ratio as a prognostic factor in patients with castration-resistant prostate cancer treated with docetaxel-based chemotherapy: a meta-analysis. BMC Urol 25, 17 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12894-024-01685-4

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BMC Urology

ISSN: 1471-2490

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