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Optimal sequencing strategy using docetaxel and androgen receptor axis-targeted agents in patients with castration-resistant prostate cancer: utilization of neutrophil-to-lymphocyte ratio

  • Kyo Chul Koo
  • Jong Soo Lee
  • Jee Soo Ha
  • Kyung Suk Han
  • Kwang Suk Lee
  • Yoon Soo Hah
  • Koon Ho Rha
  • Sung Joon Hong
  • Byung Ha ChungEmail author
Original Article
  • 9 Downloads

Abstract

Purpose

To investigate the prognostic value of neutrophil-to-lymphocyte ratio (NLR) for the selection of the optimal sequencing strategy using docetaxel and androgen receptor axis-targeted (ARAT) agents in patients with M0 or M1 castration-resistant prostate cancer (CRPC). Currently, there is a need to identify biomarkers to guide optimal sequential treatment in CRPC.

Methods

This multicenter, retrospective analysis included 303 consecutive patients initially diagnosed with M0 or M1 CRPC between September 2009 and March 2017. Of these, 52 (17.2%) patients received pre-docetaxel ARAT agents and 189 (62.4%) patients received post-docetaxel ARAT agents. The prognostic ability of NLR at CRPC diagnosis regarding radiographic progression-free survival (rPFS) and cancer-specific survival (CSS) were investigated. For the analysis, the NLR level was dichotomized at 2.5, and evaluated according to sequencing strategy.

Results

Multivariate analysis revealed NLR ≥ 2.5 as an independent predictor of a lower risk for CSS. During the median follow-up of 18.5 months, patients with NLR ≥ 2.5 exhibited significantly lower 1-year rPFS (p = 0.011) and 2-year CSS rates (p = 0.005) compared to patients with NLR < 2.5. Among patients with NLR < 2.5, the post-docetaxel ARAT agent sequencing group exhibited higher 1-year rPFS (p = 0.031) and 2-year CSS (p = 0.026) rates compared to the pre-docetaxel ARAT agent sequencing group. Among patients with NLR ≥ 2.5, rPFS and CSS rates were comparable regardless of ARAT agent sequencing.

Conclusion

NLR ≥ 2.5 at CRPC diagnosis is associated with a lower risk for CSS. Patients with NLR < 2.5 should primarily be offered docetaxel considering the survival benefit of docetaxel-to-ARAT agent sequencing.

Keywords

Docetaxel Lymphocytes Neutrophils Prostatic neoplasms Castration resistant Survival 

Notes

Acknowledgements

This study was supported by the Young Researcher Program Grant of the National Research Foundation of Korea (NRF-2017R1C1B5017516).

Author contributions

Protocol/project development: KCK, KHR, SJH, and BHC; data collection and management: JSL, JSH, KSL, and YSH; data analysis: KCK and KSH; manuscript writing/editing: Koo and Chung.

Compliance with ethical standards

Conflict of interest

All of the authors declare that they have no conflicts of interest to declare.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was not required for the purposes of this study as it was based upon retrospective anonymous patient data and did not involve patient intervention or the use of human tissue samples.

References

  1. 1.
    Tannock IF, de Wit R, Berry WR et al (2004) Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351:1502–1512CrossRefGoogle Scholar
  2. 2.
    Antonarakis ES, Lu C, Wang H et al (2014) AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med 371:1028–1038CrossRefGoogle Scholar
  3. 3.
    de Bono JS, Logothetis CJ, Molina A et al (2011) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364:1995–2005CrossRefGoogle Scholar
  4. 4.
    Ryan CJ, Smith MR, de Bono JS et al (2013) Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368:138–148CrossRefGoogle Scholar
  5. 5.
    Beer TM, Armstrong AJ, Rathkopf DE et al (2014) Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 371:424–433CrossRefGoogle Scholar
  6. 6.
    Scher HI, Fizazi K, Saad F et al (2012) Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 367:1187–1197CrossRefGoogle Scholar
  7. 7.
    Efstathiou E, Titus M, Tsavachidou D et al (2012) Effects of abiraterone acetate on androgen signaling in castrate-resistant prostate cancer in bone. J Clin Oncol 30:637–643CrossRefGoogle Scholar
  8. 8.
    Lorente D, Mateo J, Perez-Lopez R, de Bono JS, Attard G (2015) Sequencing of agents in castration-resistant prostate cancer. Lancet Oncol 16:e279–e292CrossRefGoogle Scholar
  9. 9.
    Esch L, Schulz WA, Albers P (2014) Sequential treatment with taxanes and novel anti-androgenic compounds in castration-resistant prostate cancer. Oncol Res Treat 37:492–498CrossRefGoogle Scholar
  10. 10.
    Galletti G, Leach BI, Lam L, Tagawa ST (2017) Mechanisms of resistance to systemic therapy in metastatic castration-resistant prostate cancer. Cancer Treat Rev 57:16–27CrossRefGoogle Scholar
  11. 11.
    van Soest RJ, Templeton AJ, Vera-Badillo FE et al (2015) Neutrophil-to-lymphocyte ratio as a prognostic biomarker for men with metastatic castration-resistant prostate cancer receiving first-line chemotherapy: data from two randomized phase III trials. Ann Oncol 26:743–749CrossRefGoogle Scholar
  12. 12.
    Templeton AJ, Pezaro C, Omlin A et al (2014) Simple prognostic score for metastatic castration-resistant prostate cancer with incorporation of neutrophil-to-lymphocyte ratio. Cancer 120:3346–3352CrossRefGoogle Scholar
  13. 13.
    Scher HI, Halabi S, Tannock I et al (2008) Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol 26:1148–1159CrossRefGoogle Scholar
  14. 14.
    Templeton AJ, McNamara MG, Seruga B et al (2014) Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst 106:dju124CrossRefGoogle Scholar
  15. 15.
    Leibowitz-Amit R, Templeton AJ, Omlin A et al (2014) Clinical variables associated with PSA response to abiraterone acetate in patients with metastatic castration-resistant prostate cancer. Ann Oncol 25:657–662CrossRefGoogle Scholar
  16. 16.
    Keizman D, Gottfried M, Ish-Shalom M et al (2012) Pretreatment neutrophil-to-lymphocyte ratio in metastatic castration-resistant prostate cancer patients treated with ketoconazole: association with outcome and predictive nomogram. Oncologist 17:1508–1514CrossRefGoogle Scholar
  17. 17.
    Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674CrossRefGoogle Scholar
  18. 18.
    Rashid F, Waraich N, Bhatti I et al (2010) A pre-operative elevated neutrophil: lymphocyte ratio does not predict survival from oesophageal cancer resection. World J Surg Oncol 8:1CrossRefGoogle Scholar
  19. 19.
    Donskov F, Bennedsgaard KM, Von Der Maase H et al (2002) Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival. Br J Cancer 87:194–201CrossRefGoogle Scholar
  20. 20.
    Nuhn P, Vaghasia AM, Goyal J et al (2014) 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 114:E11–E17CrossRefGoogle Scholar
  21. 21.
    Gabay C, Kushner I (1999) Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340:448–454CrossRefGoogle Scholar
  22. 22.
    Loriot Y, Bianchini D, Ileana E et al (2013) Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100). Ann Oncol 24:1807–1812CrossRefGoogle Scholar
  23. 23.
    Crawford ED, Higano CS, Shore ND, Hussain M, Petrylak DP (2015) Treating patients with metastatic castration resistant prostate cancer: a comprehensive review of available therapies. J Urol 194:1537–1547CrossRefGoogle Scholar
  24. 24.
    Izumi K, Li L, Chang C (2014) Androgen receptor and immune inflammation in benign prostatic hyperplasia and prostate cancer. Clin Investig (Lond) 4:935–950CrossRefGoogle Scholar
  25. 25.
    Thapa D, Ghosh R (2015) Chronic inflammatory mediators enhance prostate cancer development and progression. Biochem Pharmacol 94:53–62CrossRefGoogle Scholar
  26. 26.
    Sciarra A, Casale P, Colella D, Di Chiro C, Di Silverio F (1999) Hormone-refractory prostate cancer? Anti-androgen withdrawal and intermittent hormonetherapy. Scand J Urol Nephrol 33:211–216CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Urology, Gangnam Severance HospitalYonsei University College of MedicineSeoulRepublic of Korea
  2. 2.Department of Urology, Severance HospitalYonsei University College of MedicineSeoulRepublic of Korea

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