Skip to main content

Advertisement

SpringerLink
Log in

Significance of baseline bone markers on disease progression and survival in hormone-sensitive prostate cancer with bone metastasis

  • Original Article
  • Published:
World Journal of Urology Aims and scope Submit manuscript

Abstract

Purpose

This study evaluated the baseline patient characteristics associated with the time to biochemical progression and overall survival in patients who participated in a phase II trial on zoledronic acid combined with the initial androgen-deprivation therapy for treatment-naïve bone-metastatic prostate cancer.

Methods

Patients received zoledronic acid 4 mg intravenously every 4 weeks for up to 24 months, concomitantly started with bicalutamide 80 mg orally every day and goserelin acetate 10.8 mg subcutaneously every 12 weeks.

Results

A total of 53 Japanese patients were enrolled between July 2008 and April 2010, and 52 patients were evaluable. Median follow-up period was 41.6 months. Updated median time to biochemical progression was 25.9 months (95 % confidence interval 14.5–49.9). Higher serum bone-specific alkaline phosphatase was an independent risk factor for time to biochemical progression based on multivariate analysis (hazard ratio 6.51; 95 % confidence interval 2.71–15.62; P < 0.001). Median time to biochemical progression for patients with serum bone-specific alkaline phosphatase level higher than 26 μg/L was 12.7 months. Multivariate analysis indicated that higher serum C-terminal telopeptide of type I collagen independently increased the risk of death (hazard ratio 9.62; 95 % confidence interval 2.11–43.89; P = 0.003). Median overall survival for patients with serum C-terminal telopeptide of type I collagen level higher than 8.0 ng/ml was 31.1 months.

Conclusions

Baseline bone markers can be useful as predictors for disease progression and survival time in patients with bone metastasis from treatment-naïve prostate cancer treated with upfront zoledronic acid concomitantly started with androgen-deprivation therapy.

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.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Coleman RE (2004) Bisphosphonates: clinical experience. Oncologist 9:14–27

    Article  CAS  PubMed  Google Scholar 

  2. Oefelein MG, Ricchiuti V, Conrad W, Resnick MI (2002) Skeletal fractures negatively correlate with overall survival in men with prostate cancer. J Urol 168:1005–1007

    Article  PubMed  Google Scholar 

  3. Nørgaard M, Jensen AØ, Jacobsen JB, Cetin K, Fryzek JP, Sørensen HT (2010) Skeletal related events, bone metastasis and survival of prostate cancer: a population based cohort study in Denmark (1999 to 2007). J Urol 184:162–167

    Article  PubMed  Google Scholar 

  4. Sathiakumar N, Delzell E, Morrisey MA et al (2011) Mortality following bone metastasis and skeletal-related events among men with prostate cancer: a population-based analysis of US medicare beneficiaries, 1999–2006. Prostate Cancer Prostatic Dis 14:177–183

    Article  CAS  PubMed  Google Scholar 

  5. Saad F, Gleason DM, Murray R et al (2002) A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 94:1458–1468

    Article  CAS  PubMed  Google Scholar 

  6. Nozawa M, Inagaki T, Nagao K et al (2014) Phase II trial of zoledronic acid combined with androgen-deprivation therapy for treatment-naïve prostate cancer with bone metastasis. Int J Clin Oncol 19:693–701

    Article  CAS  PubMed  Google Scholar 

  7. 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 26:1148–1159

    Article  PubMed Central  PubMed  Google Scholar 

  8. Maeda H, Koizumi M, Yoshimura K, Yamauchi T, Kawai T, Ogata E (1997) Correlation between bone metabolic markers and bone scan in prostatic cancer. J Urol 157:539–543

    Article  CAS  PubMed  Google Scholar 

  9. Aruga A, Koizumi M, Hotta R, Takahashi S, Ogata E (1997) Usefulness of bone metabolic markers in the diagnosis and follow-up of bone metastasis from lung cancer. Br J Cancer 76:760–764

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Cook RJ, Coleman R, Brown J et al (2006) Markers of bone metabolism and survival in men with hormone-refractory metastatic prostate cancer. Clin Cancer Res 12:3361–3367

    Article  CAS  PubMed  Google Scholar 

  11. Smith MR, Cook RJ, Coleman R et al (2007) Predictors of skeletal complications in men with hormone-refractory metastatic prostate cancer. Urology 70:315–319

    Article  PubMed Central  PubMed  Google Scholar 

  12. Lara PN Jr, Ely B, Quinn DI et al (2014) Serum biomarkers of bone metabolism in castration-resistant prostate cancer patients with skeletal metastases: results from SWOG 0421. J Natl Cancer Inst 106: dju013

  13. Berruti A, Dogliotti L, Gorzegno G et al (1999) Differential patterns of bone turnover in relation to bone pain and disease extent in bone in cancer patients with skeletal metastases. Clin Chem 45:1240–1247

    CAS  PubMed  Google Scholar 

  14. Hollier BG, Evans K, Mani SA (2009) The epithelial-to-mesenchymal transition and cancer stem cells: a coalition against cancer therapies. J Mammary Gland Biol Neoplasia 14:29–43

    Article  PubMed  Google Scholar 

  15. Lévesque JP, Helwani FM, Winkler IG (2010) The endosteal ‘osteoblastic’ niche and its role in hematopoietic stem cell homing and mobilization. Leukemia 24:1979–1992

    Article  PubMed  Google Scholar 

  16. Sun Y, Wang BE, Leong KG et al (2012) Androgen deprivation causes epithelial-mesenchymal transition in the prostate: implications for androgen-deprivation therapy. Cancer Res 72:527–536

    Article  CAS  PubMed  Google Scholar 

  17. Fizazi K, Carducci M, Smith M et al (2011) Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 377:813–822

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Parker C, Nilsson S, Heinrich D et al (2013) Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 369:213–223

    Article  CAS  PubMed  Google Scholar 

  19. Smith DC, Smith MR, Sweeney C et al (2013) Cabozantinib in patients with advanced prostate cancer: results of a phase II randomized discontinuation trial. J Clin Oncol 31:412–419

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Brown JE, Cook RJ, Major P et al (2005) Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors. J Natl Cancer Inst 97:59–69

    Article  CAS  PubMed  Google Scholar 

  21. Sweeney CJ (2006) ECOG: CHAARTED–ChemoHormonal therapy versus androgen ablation randomized trial for extensive disease in prostate cancer. Clin Adv Hematol Oncol 4:588–590

    PubMed  Google Scholar 

  22. Tombal B, Borre M, Rathenborg P et al (2014) Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study. Lancet Oncol 15:592–600

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank all patients and their families for participating in this study, all investigators and site staff for their contribution, and Marco De Velasco for reviewing the language.

Conflict of interest

The authors have no conflict of interest.

Ethical standard

The study was conducted according to the Declaration of Helsinki with approval from ethics committees at each institution. Written informed consent was obtained from all patients consistent with local requirements.

Author information

Authors and Affiliations

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

    Masahiro Nozawa & Hirotsugu Uemura

  2. Department of Urology, Wakayama Medical University, Wakayama, Japan

    Isao Hara

  3. Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, Japan

    Hideyasu Matsuyama & Kazuhiro Nagao

  4. Department of Public Health, Faculty of Medicine, Kinki University, Osaka-Sayama, Japan

    Masayuki Iki

  5. Department of Urology, Sakai Hospital, Faculty of Medicine, Kinki University, Sakai, Japan

    Tsukasa Nishioka

  6. Department of Urology, Naga Hospital, Kinokawa, Japan

    Takahiro Komura

  7. Department of Urology, NTT Osaka Hospital, Osaka, Japan

    Atsunobu Esa

  8. Department of Urology, National Hospital Organization Osaka Minami Medical Center, Kawachinagano, Japan

    Shigeya Uejima

  9. Department of Urology, Tondabayashi Hospital, Tondabayashi, Japan

    Masaaki Imanishi

  10. Department of Urology, Wakayama Rosai Hospital, Wakayama, Japan

    Yasunari Uekado

  11. Department of Urology, Kainan Municipal Hospital, Kainan, Japan

    Takatoshi Ogawa

  12. Department of Urology, Izumiotsu Municipal Hospital, Izumiotsu, Japan

    Hiroshi Kajikawa

Authors
  1. Masahiro Nozawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Isao Hara
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hideyasu Matsuyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masayuki Iki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kazuhiro Nagao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tsukasa Nishioka
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Takahiro Komura
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Atsunobu Esa
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shigeya Uejima
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Masaaki Imanishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yasunari Uekado
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Takatoshi Ogawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Hiroshi Kajikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Hirotsugu Uemura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masahiro Nozawa.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nozawa, M., Hara, I., Matsuyama, H. et al. Significance of baseline bone markers on disease progression and survival in hormone-sensitive prostate cancer with bone metastasis. World J Urol 33, 1263–1268 (2015). https://doi.org/10.1007/s00345-014-1431-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00345-014-1431-1

Keywords

Search

Navigation