Skip to main content

Advertisement

SpringerLink
Log in

The presence of lymph node metastases and time to castration resistance predict the therapeutic effect of enzalutamide for castration-resistant prostate cancer

  • Original Article
  • Published:
International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

Enzalutamide is effective against castration-resistant prostate cancer (CRPC). However, it is unclear which patients would benefit more from enzalutamide treatment. Here, we analyzed patients who received enzalutamide as first-line therapy for CRPC and evaluated the factors that predict treatment response and prognosis.

Methods

We retrospectively analyzed 101 patients treated with enzalutamide for CRPC at our institution. As primary endpoints we regarded the prostate-specific antigen (PSA) response rate and PSA–progression-free survival (PSA–PFS) from the start of enzalutamide treatment. Laboratory and imaging data were analyzed to predict treatment efficacy.

Results

PSA reductions of ≥ 50% and ≥ 90% were observed in 78 (77%) and 47 (47%) patients, respectively, compared with the baseline. During the follow-up period, 67 (66%) patients showed PSA progression, with a median PSA–PFS of 11 months. Moreover, 31 patients (31%) died, with a median overall survival of 64 months. On multivariate analysis, lymph node metastases at the start of enzalutamide treatment [odds ratio (OR) 0.0575, 95% confidence interval (CI) 0.0105–0.316, p = 0.0010] and time to CRPC (OR 0.177, 95% CI 0.0428–0.731, p = 0.0167] were associated with ≥ 90% PSA response. Lymph node metastases (hazard ratio [HR] 3.00, 95% CI 1.48–6.09, p = 0.0023) and time to CRPC (HR 1.84, 95% CI 1.02–3.30, p = 0.0419) were also predictors of PSA–PFS on a multivariate model.

Conclusions

Time to CRPC and lymph node metastasis were predictors of the PSA response rate and PSA–PFS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

Raw data were generated at Osaka University. Derived data supporting the results of this study are available upon request from the corresponding author, KH.

References

  1. Siegel RL, Miller KD, Fuchs HE et al (2022) Cancer statistics, 2022. CA Cancer J Clin 72:7–33

    Article  PubMed  Google Scholar 

  2. Li J, Siegel DA, King JB (2018) Stage-specific incidence rates and trends of prostate cancer by age, race, and ethnicity, United States, 2004–2014. Ann Epidemiol 28:328–330

    Article  PubMed  PubMed Central  Google Scholar 

  3. Ritch C, Cookson M (2018) Recent trends in the management of advanced prostate cancer. F1000 Fac Rev 1513(7):F1000Res

    Google Scholar 

  4. Taylor BS, Schultz N, Hieronymus H et al (2010) Integrative genomic profiling of human prostate cancer. Cancer Cell 18:11–22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Steele CB, Li J, Huang B et al (2017) Prostate cancer survival in the United States by race and stage (2001–2009): findings from the CONCORD-2 study. Cancer 123(Suppl 24):5160–5177

    Article  PubMed  Google Scholar 

  6. Ryan CJ, Smith MR, de Bono JS et al (2013) Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368:138–148

    Article  CAS  PubMed  Google Scholar 

  7. Beer TM, Armstrong AJ, Rathkopf DE et al (2014) Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med 371:424–433

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ryan CJ, Kheoh T, Li J et al (2017) Prognostic index model for progression-free survival in chemotherapy-naïve metastatic castration-resistant prostate cancer treated with abiraterone acetate plus prednisone. Clin Genitourin Cancer S1558–7673(17):30211–30212

    Google Scholar 

  9. Sweeney CJ, Chen YH, Carducci M et al (2015) Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 373:737–746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chikamatsu S, Shiota M, Yamada S et al (2022) Prognostic significance of risk stratification in CHAARTED and LATITUDE studies among Japanese men with castration-resistant prostate cancer. Prostate Int 10:7–13

    Article  PubMed  PubMed Central  Google Scholar 

  11. Hatakeyama S, Narita S, Takahashi M et al (2020) Association of tumor burden with the eligibility of upfront intensification therapy in metastatic castration-sensitive prostate cancer: a multicenter retrospective study. Int J Urol 27:610–617

    Article  CAS  PubMed  Google Scholar 

  12. Armstrong AJ, Lin P, Higano CS et al (2019) Prognostic association of prostate-specific antigen decline with clinical outcomes in men with metastatic castration-resistant prostate cancer treated with enzalutamide in a randomized clinical trial. Eur Urol Oncol 2:677–684

    Article  PubMed  Google Scholar 

  13. Scher HI, Morris MJ, Stadler WM et al (2016) Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the prostate cancer clinical trials working group 3. J Clin Oncol 34:1402–1418

    Article  PubMed  PubMed Central  Google Scholar 

  14. Scher HI, Fizazi K, Saad F et al (2012) Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 367:1187–1197

    Article  CAS  PubMed  Google Scholar 

  15. Halabi S, Kelly WK, Ma H et al (2016) Meta-analysis evaluating the impact of site of metastasis on overall survival in men with castration-resistant prostate cancer. J Clin Oncol 34:1652–1659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Francini E, Gray KP, Xie W et al (2018) Time of metastatic disease presentation and volume of disease are prognostic for metastatic hormone sensitive prostate cancer (mHSPC). Prostate 78:889–895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cho S, Kang SG, Tae BS et al (2012) Influence of nonregional lymph node metastasis as a prognostic factor in metastatic prostate cancer patients. Korean J Urol 53:673–679

    Article  PubMed  PubMed Central  Google Scholar 

  18. Ali A, Hoyle A, Mistry H et al (2019) Importance of non-regional lymph nodes in assigning risk in primary metastatic prostate cancer. BJU Int 123:65–73

    Article  PubMed  Google Scholar 

  19. Narita S, Hatakeyama S, Takahashi M et al (2020) Clinical outcomes and prognostic factors in patients with newly diagnosed metastatic prostate cancer initially treated with androgen deprivation therapy: a retrospective multicenter study in Japan. Int J Clin Oncol 25:912–920

    Article  CAS  PubMed  Google Scholar 

  20. Bournakis E, Efstathiou E, Varkaris A et al (2011) Time to castration resistance is an independent predictor of castration-resistant prostate cancer survival. Anticancer Res 31:1475–1482

    PubMed  Google Scholar 

  21. Frees S, Akamatsu S, Bidnur S et al (2018) The impact of time to metastasis on overall survival in patients with prostate cancer. World J Urol 36:1039–1046

    Article  PubMed  Google Scholar 

  22. Loriot Y, Eymard JC, Patrikidou A et al (2015) Prior long response to androgen deprivation predicts response to next-generation androgen receptor axis targeted drugs in castration resistant prostate cancer. Eur J Cancer 51:1946–1952

    Article  CAS  PubMed  Google Scholar 

  23. Ross RW, Oh WK, Xie W et al (2008) Inherited variation in the androgen pathway is associated with the efficacy of androgen-deprivation therapy in men with prostate cancer. J Clin Oncol 26:842–847

    Article  PubMed  Google Scholar 

  24. Yang M, Xie W, Mostaghel E et al (2011) SLCO2B1 and SLCO1B3 may determine time to progression for patients receiving androgen deprivation therapy for prostate cancer. J Clin Oncol 29:2565–2573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. 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 26:743–749

    Article  PubMed  Google Scholar 

  26. Shimabukuro T, Sakano S, Matsuda K et al (2013) Can docetaxel therapy improve overall survival from primary therapy compared with androgen-deprivation therapy alone in Japanese patients with castration-resistant prostate cancer? A multi-institutional cooperative study. Int J Clin Oncol 18:62–67

    Article  CAS  PubMed  Google Scholar 

  27. Shigeta K, Kosaka T, Hongo H et al (2019) Castration-resistant prostate cancer patients who had poor response on first androgen deprivation therapy would obtain certain clinical benefit from early docetaxel administration. Int J Clin Oncol 24:546–553

    Article  CAS  PubMed  Google Scholar 

  28. Chi KN, Kheoh T, Ryan CJ et al (2016) A prognostic index model for predicting overall survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate after docetaxel. Ann Oncol 27:454–460

    Article  CAS  PubMed  Google Scholar 

  29. Miyazawa Y, Sekine Y, Arai S et al (2021) A prospective study of the relationship between clinical outcomes after enzalutamide and serum androgen levels measured via liquid chromatography-tandem mass spectrometry in patients with castration-resistant prostate cancer. Eur Urol Open Sci 29:59–67

    Article  PubMed  PubMed Central  Google Scholar 

  30. 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 351:1502–1512

    Article  CAS  PubMed  Google Scholar 

  31. 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 120:3346–3352

    Article  CAS  PubMed  Google Scholar 

  32. Shiota M, Kashiwagi E, Murakami T et al (2019) Serum testosterone level as possible predictive marker in androgen receptor axis-targeting agents and taxane chemotherapies for castration-resistant prostate cancer. Urol Oncol 37:180.e19-180.e24

    Article  CAS  PubMed  Google Scholar 

  33. Sakamoto S, Maimaiti M, Xu M et al (2019) Higher serum testosterone levels associated with favorable prognosis in enzalutamide- and abiraterone-treated castration-resistant prostate cancer. J Clin Med 8:489

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank Editage (http://www.editage.com) for English language editing.

Funding

This work was supported by the Japan Society for the Promotion of Science KAKENHI [Grant number 22K09447].

Author information

Authors and Affiliations

  1. Department of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Toshiki Oka, Koji Hatano, Yohei Okuda, Akinaru Yamamoto, Toshihiro Uemura, Gaku Yamamichi, Eisuke Tomiyama, Yu Ishizuya, Yoshiyuki Yamamoto, Taigo Kato, Atsunari Kawashima & Norio Nonomura

  2. Department of Urology, Kindai University Faculty of Medicine, 377-2, Ohno-Higashi, Sayama, Osaka, 589-8511, Japan

    Kazutoshi Fujita

Authors
  1. Toshiki Oka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Koji Hatano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yohei Okuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Akinaru Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Toshihiro Uemura
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gaku Yamamichi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Eisuke Tomiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yu Ishizuya
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yoshiyuki Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Taigo Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Atsunari Kawashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Kazutoshi Fujita
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Norio Nonomura
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

TO and KH contributed to the study conception and design. Material preparation and data collection and analysis were performed by TO, KH, YO, AY, TU, GY, ET, YI, YY, TK, AK, KF, and NN. Data analysis was performed by TO. The first draft of the manuscript was written by TO, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Koji Hatano.

Ethics declarations

Conflict of interest

KH and NN have the following potential conflict of interest to report: receipt of Grants/research supports: Astellas Global.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 16 KB)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Oka, T., Hatano, K., Okuda, Y. et al. The presence of lymph node metastases and time to castration resistance predict the therapeutic effect of enzalutamide for castration-resistant prostate cancer. Int J Clin Oncol 28, 427–435 (2023). https://doi.org/10.1007/s10147-022-02288-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-022-02288-5

Keywords

Search

Navigation