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

Abstract

Background

The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR), as markers of systematic inflammation response, have been reported to be indicators in metastatic castration-resistant prostate cancer (mCRPC), whereas their prognostic values remain conflict. This study was to assess the prognostic value of NLR and PLR in mCRPC patients and to assess the response of abiraterone or enzalutamide through using NLR and PLR.

Methods

Databases searching was conducted in the PubMed, EMBASE, Google Scholar, and the Cochrane Library for relevant published literature up to October 2019. Data extraction and quality evaluation were performed on the eligible studies. STATA 14.0 software was used to pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS).

Results

A total of 3144 mCRPC patients were enrolled from 15 cohort studies in this meta-analysis. The pooled results demonstrated that elevated NLR had a significant association with inferior OS in mCRPC patients treated with abiraterone (HR = 1.63, 95% CI: 1.43–1.85, P < 0.001) and enzalutamide (HR = 1.48, 95% CI: 1.27–1.72, P < 0.001), whereas elevated NLR had no significant association with unfavorable PFS treated with abiraterone and enzalutamide, respectively. Elevated PLR had a significant association with an inferior OS (HR = 1.52, 95% CI: 1.16–1.98, P < 0.001) in mCRPC patients treated with abiraterone.

Conclusions

NLR and PLR were effective biomarkers for predicting prognosis in mCRPC patients and served as indicators of the efficacy of personalized treatment of mCRPC using abiraterone or enzalutamide. Future, more randomized control trials (RCTs) are needed to investigate the promising value of hematologic parameters.

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Fig. 1
Fig. 2: Forest plots of pooled NLR on OS in mCRPC patients.
Fig. 3
Fig. 4: Forest plots of pooled NLR on PFS in mCRPC patients.
Fig. 5
Fig. 6: Sensitivity analysis and Egger's test of pooled NLR on OS in mCRPC patients.

References

  1. 1.

    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7–34.

    PubMed  PubMed Central  Article  Google Scholar 

  2. 2.

    Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol. 2017;71:618–29.

    PubMed  Article  Google Scholar 

  3. 3.

    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;71:630–42.

    PubMed  Article  Google Scholar 

  4. 4.

    Handy CE, Antonarakis ES. Sipuleucel-T for the treatment of prostate cancer: novel insights and future directions. Future Oncol. 2018;14:907–17.

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368:138–48.

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Higano C. Enzalutamide, apalutamide, or darolutamide: are apples or bananas best for patients? Nat Rev Urol. 2019;16:335–6.

    PubMed  Article  Google Scholar 

  7. 7.

    Schalken J, Fitzpatrick JM. Enzalutamide: targeting the androgen signalling pathway in metastatic castration-resistant prostate cancer. BJU Int. 2016;117:215–25.

    CAS  PubMed  Article  Google Scholar 

  8. 8.

    Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fosså SD, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Antonarakis ES, Lu C, Wang H, Luber B, Nakazawa M, Roeser JC, et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med. 2014;371:1028–38.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  10. 10.

    Shaul ME, Fridlender ZG. Tumour-associated neutrophils in patients with cancer. Nat Rev Clin Oncol. 2019;16:601–20.

    PubMed  Article  Google Scholar 

  11. 11.

    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;120:3346–52.

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    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.

    PubMed  Article  Google Scholar 

  13. 13.

    Yasui M, Hasegawa Y, Kawahara T, Kumano Y, Miyoshi Y, Matsubara N, et al. Baseline neutrophil-to-lymphocyte ratio predicts the prognosis of castration-resistant prostate cancer treated with abiraterone acetate. Mol Clin Oncol. 2018;8:592–4.

    Google Scholar 

  14. 14.

    Loubersac T, Nguile-Makao M, Pouliot F, Fradet V, Toren P. Neutrophil-to-lymphocyte ratio as a predictive marker of response to abiraterone acetate: a retrospective analysis of the COU302 study. Eur Urol Oncol. 2019;1:e144.

  15. 15.

    Conteduca V, Crabb SJ, Jones RJ, Caffo O, Elliott T, Scarpi E, et al. Persistent neutrophil to lymphocyte ratio >3 during treatment with enzalutamide and clinical outcome in patients with castration-resistant prostate cancer. PLoS ONE. 2016;11:e0158952.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  16. 16.

    Kumano Y, Hasegawa Y, Kawahara T, Yasui M, Miyoshi Y, Matsubara N, et al. Pretreatment neutrophil to lymphocyte ratio (NLR) predicts prognosis for castration resistant prostate cancer patients underwent enzalutamide. Biomed Res Int. 2019;2019:9450838.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  17. 17.

    Choi SY, Ryu J, You D, Jeong IG, Hong JH, Ahn H, et al. Prognostic factors of oncologic outcomes in metastatic chemotherapy-naive castration-resistant prostate cancer treated with enzalutamide in actual clinical practice in East Asia. Urol Oncol. 2018;36:401 e411–401 e418.

    Article  Google Scholar 

  18. 18.

    Lolli C, Caffo O, Scarpi E, Aieta M, Conteduca V, Maines F, et al. Systemic immune-inflammation index predicts the clinical outcome in patients with mCRPC treated with abiraterone. Front Pharmacol. 2016;7:376.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. 19.

    Lozano Martinez AJ, Moreno Cano R, Escobar Paramo S, Salguero Aguilar R, Gonzalez Billalabeitia E, Garcia Fernandez R, et al. Platelet-lymphocyte and neutrophil-lymphocyte ratios are prognostic but not predictive of response to abiraterone acetate in metastatic castration-resistant prostate cancer. Clin Transl Oncol. 2017;19:1531–6.

    CAS  PubMed  Article  Google Scholar 

  20. 20.

    Boegemann M, Schlack K, Früchtenicht L, Steinestel J, Schrader AJ, Wennmann Y, et al. A prognostic score for overall survival in patients treated with abiraterone in the pre- and post-chemotherapy setting. Oncotarget. 2019;10:5082–91.

    PubMed  PubMed Central  Article  Google Scholar 

  21. 21.

    Onal C, Sedef AM, Kose F, Oymak E, Guler OC, Sumbul AT, et al. The hematologic parameters in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate. Future Oncol. 2019;15:1469–79.

    PubMed  Article  Google Scholar 

  22. 22.

    Boegemann M, Schlack K, Thomes S, Steinestel J, Rahbar K, Semjonow A, et al. The role of the neutrophil to lymphocyte ratio for survival outcomes in patients with metastatic castration-resistant prostate cancer treated with abiraterone. Int J Mol Sci. 2017;18:380.

  23. 23.

    Conteduca V, Caffo O, Galli L, Maugeri A, Scarpi E, Maines F, et al. Association among metabolic syndrome, inflammation, and survival in prostate cancer. Urol Oncol. 2018;36:240 e241–240 e211.

    Article  CAS  Google Scholar 

  24. 24.

    Schiff JP, Cotogno P, Feibus A, Steinwald P, Ledet E, Lewis B, et al. Early prostate-specific antigen response post-abiraterone as predictor of overall survival in metastatic castrate-resistant prostate cancer. BMC Cancer. 2019;19:524.

    PubMed  PubMed Central  Article  Google Scholar 

  25. 25.

    Fan L, Wang X, Chi C, Wang Y, Cai W, Shao X, et al. Prognostic nutritional index predicts initial response to treatment and prognosis in metastatic castration-resistant prostate cancer patients treated with abiraterone. Prostate. 2017;77:1233–41.

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Armstrong AJ, Lin P, Higano CS, Sternberg CN, Sonpavde G, Tombal B, et al. Development and validation of a prognostic model for overall survival in chemotherapy-naive men with metastatic castration-resistant prostate cancer. Ann Oncol. 2018;29:2200–7.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  27. 27.

    Litwin MS, Tan HJ. The diagnosis and treatment of prostate cancer: a review. JAMA. 2017;317:2532–42.

    PubMed  Article  Google Scholar 

  28. 28.

    Guo J, Fang J, Huang X, Liu Y, Yuan Y, Zhang X, et al. Prognostic role of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in prostate cancer: a meta-analysis of results from multivariate analysis. Int J Surg. 2018;60:216–23.

    PubMed  Article  Google Scholar 

  29. 29.

    Peng H, Luo X. Prognostic significance of elevated pretreatment systemic inflammatory markers for patients with prostate cancer: a meta-analysis. Cancer Cell Int. 2019;19:70.

    PubMed  PubMed Central  Article  Google Scholar 

  30. 30.

    Wang Z, Peng S, Xie H, Guo L, Jiang N, Shang Z, et al. Neutrophil-lymphocyte ratio is a predictor of prognosis in patients with castration-resistant prostate cancer: a meta-analysis. Cancer Manag Res. 2018;10:3599–610.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. 31.

    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. Medicine. 2016;95:e2544.

    PubMed  PubMed Central  Article  Google Scholar 

  32. 32.

    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.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  33. 33.

    Li DY, Hao XY, Ma TM, Dai HX, Song YS. The prognostic value of platelet-to-lymphocyte ratio in urological cancers: a meta-analysis. Sci Rep. 2017;7:15387.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  34. 34.

    Ohno Y. Role of systemic inflammatory response markers in urological malignancy. Int J Urol. 2019;26:31–47.

    CAS  PubMed  Article  Google Scholar 

  35. 35.

    Shaul ME, Fridlender ZG. Cancer-related circulating and tumor-associated neutrophils—subtypes, sources and function. FEBS J. 2018;285:4316–42.

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    Li M, Deng Q, Zhang L, He S, Rong J, Zheng F. The pretreatment lymphocyte to monocyte ratio predicts clinical outcome for patients with urological cancers: a meta-analysis. Pathol Res Pr. 2019;215:5–11.

    Article  Google Scholar 

  37. 37.

    Caglayan V, Onen E, Avci S, Sambel M, Kilic M, Oner S, et al. Lymphocyte-to-monocyte ratio is a valuable marker to predict prostate cancer in patients with prostate specific antigen between 4 and 10 ng/dl. Arch Ital Urol Androl. 2019;90:270–5.

    PubMed  Article  CAS  Google Scholar 

  38. 38.

    Diem S, Schmid S, Krapf M, Flatz L, Born D, Jochum W, et al. Neutrophil-to-Lymphocyte ratio (NLR) and Platelet-to-Lymphocyte ratio (PLR) as prognostic markers in patients with non-small cell lung cancer (NSCLC) treated with nivolumab. Lung Cancer. 2017;111:176–81.

    PubMed  Article  Google Scholar 

  39. 39.

    Guo W, Lu X, Liu Q, Zhang T, Li P, Qiao W, et al. Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for breast cancer patients: an updated meta-analysis of 17079 individuals. Cancer Med. 2019;8:4135–48.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Ferrucci PF, Ascierto PA, Pigozzo J, Del Vecchio M, Maio M, Antonini Cappellini GC, et al. Baseline neutrophils and derived neutrophil-to-lymphocyte ratio: prognostic relevance in metastatic melanoma patients receiving ipilimumab. Ann Oncol. 2016;27:732–8.

    CAS  PubMed  Article  Google Scholar 

  41. 41.

    Haram A, Boland MR, Kelly ME, Bolger JC, Waldron RM, Kerin MJ. The prognostic value of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review. J Surg Oncol. 2017;115:470–9.

    CAS  PubMed  Article  Google Scholar 

  42. 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;115:718–28.

    CAS  PubMed  Article  Google Scholar 

  43. 43.

    Lucca I, Jichlinski P, Shariat SF, Roupret M, Rieken M, Kluth LA, et al. The neutrophil-to-lymphocyte ratio as a prognostic factor for patients with urothelial carcinoma of the bladder following radical cystectomy: validation and meta-analysis. Eur Urol Focus. 2016;2:79–85.

    PubMed  Article  Google Scholar 

  44. 44.

    Dupre A, Malik HZ. Inflammation and cancer: what a surgical oncologist should know. Eur J Surg Oncol. 2018;44:566–70.

    PubMed  Article  Google Scholar 

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Acknowledgements

We greatly acknowledge Prof. Qianyun Tang, from Central South University, for her excellent advice on the paper.

Funding

This study was funded by the National Natural Science Foundation of China (Grant Number: 81772754) and the Guangdong Provincial Natural Science Foundation-Major Basic Research and Cultivation Project, China (Grant Number: 2017A030308009).

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Conceptualization: YG and HX. Methodology: YG, YF, and GL. Writing, editing, and revision: YG. Supervision and review: JP.

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Correspondence to Jun Pang.

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Guan, Y., Xiong, H., Feng, Y. et al. 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 23, 220–231 (2020). https://doi.org/10.1038/s41391-020-0209-3

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