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International Journal of Clinical Oncology

, Volume 20, Issue 5, pp 1018–1025 | Cite as

Neoadjuvant luteinizing-hormone-releasing hormone agonist plus low-dose estramustine phosphate improves prostate-specific antigen-free survival in high-risk prostate cancer patients: a propensity score-matched analysis

  • Takuya KoieEmail author
  • Koji Mitsuzuka
  • Takahiro Yoneyama
  • Shintaro Narita
  • Sadafumi Kawamura
  • Yasuhiro Kaiho
  • Norihiko Tsuchiya
  • Tatsuo Tochigi
  • Tomonori Habuchi
  • Yoichi Arai
  • Chikara Ohyama
  • Tohru Yoneyama
  • Yuki Tobisawa
Original Article

Abstract

Background

The optimal treatment for high-risk prostate cancer (Pca) remains to be established. We previously reported favorable biochemical recurrence-free survival (BRFS) in high-risk Pca patients treated with a neoadjuvant therapy comprising a luteinizing-hormone-releasing hormone (LHRH) agonist plus low dose estramustine phosphate (EMP) (LHRH+EMP) followed by radical prostatectomy (RP). In the present study, we used a retrospective design via propensity score matching to elucidate the clinical benefit of neoadjuvant LHRH+EMP for high-risk Pca.

Methods

The Michinoku Urological Cancer Study Group database contained data for 1,268 consecutive Pca patients treated with RP alone at 4 institutions between April 2000 and March 2011 (RP alone group). In the RP alone group, we identified 386 high-risk Pca patients. The neoadjuvant LHRH+EMP group included 274 patients with high-risk Pca treated between September 2005 and November 2013 at Hirosaki University. Neoadjuvant LHRH+EMP therapy included LHRH and EMP administration at a dose of 280 mg/day for 6 months before RP. The outcome measures were overall survival (OS) and BRFS.

Results

The propensity score-matched analysis indicated 210 matched pairs from both groups. The 5-year BRFS rates were 90.4 and 65.8 % for the neoadjuvant LHRH+EMP and RP alone groups, respectively (P < 0.0001). The 5-year OS rates were 100 and 96.1 % for the neoadjuvant LHRH+EMP and RP alone groups, respectively (P = 0.110).

Conclusions

Although the present study was not randomized, neoadjuvant LHRH+EMP therapy followed by RP appeared to reduce the risk of biochemical recurrence. A prospective randomized study is warranted to determine the clinical implications of the neoadjuvant therapy described here.

Keywords

High-risk prostate cancer Prostatectomy Neoadjuvant therapy LHRH plus estramustine Propensity score analysis 

Notes

Conflict of interest

No author has any conflict of interest.

References

  1. 1.
    Lester-Coll NH, Goldhaber SZ, Sher DJ et al (2013) Death from high-risk prostate cancer versus cardiovascular mortality with hormone therapy. Cancer 119:1808–1815CrossRefPubMedGoogle Scholar
  2. 2.
    Yuh B, Artibani W, Heidenreich A et al (2013) The role of robot-assisted radical prostatectomy and pelvic lymph node dissection in the management of high-risk prostate cancer: a systematic review. Eur Urol 65:918–927CrossRefPubMedGoogle Scholar
  3. 3.
    Yossepowitch O, Eggener SE, Serio AM et al (2008) Secondary therapy, metastatic progression, and cancer-specific mortality in men with clinically high-risk prostate cancer treated with radical prostatectomy. Eur Urol 53:950–959PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Loeb S, Schaeffer EM, Trock BJ et al (2010) What are the outcomes of radical prostatectomy for high-risk prostate cancer? Urology 76:710–714PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Gleave ME, Goldenberg SL, Chin JL et al (2001) Randomized comparative study of 3 versus 8-months neoadjuvant hormonal therapy before radical prostatectomy: biochemical and pathological effects. J Urol 166:500–507CrossRefPubMedGoogle Scholar
  6. 6.
    Chi KN, Chin JL, Winquist E et al (2008) Multicenter phase II study of combined neoadjuvant docetaxel and hormone therapy before radical prostatectomy for patients with high risk localized prostate cancer. J Urol 180:565–570CrossRefPubMedGoogle Scholar
  7. 7.
    Prayer-Galetti T, Sacco E, Pagano F et al (2007) Long-term follow-up of a neoadjuvant chemohormonal taxane-based phase II trial before radical prostatectomy in patients with non-metastatic high-risk prostate cancer. BJU Int 100:274–280CrossRefPubMedGoogle Scholar
  8. 8.
    Magi-Galluzzi C, Zhou M, Reuther AM et al (2007) Neoadjuvant docetaxel treatment for locally advanced prostate cancer: a clinicopathologic study. Cancer 110:1248–1254CrossRefPubMedGoogle Scholar
  9. 9.
    Speicher LA, Laing N, Barone LR et al (1994) Interaction of an estramustine photoaffinity analogue with cytoskeletal proteins in prostate carcinoma cells. Mol Pharmacol 46:866–872PubMedGoogle Scholar
  10. 10.
    Koie T, Ohyama C, Yamamoto H et al (2012) Safety and effectiveness of neoadjuvant luteinizing hormone-releasing hormone agonist plus low-dose estramustine phosphate in high-risk prostate cancer: a prospective single-arm study. Prostate Cancer Prostatic Dis 15:397–401CrossRefPubMedGoogle Scholar
  11. 11.
    American Joint Committee on Cancer (AJCC) (2010) Prostate. In: Edge SB, Byrd DR, Compton CC et al (eds) AJCC Cancer Staging Manual, 7th edn. Springer, New York, pp 457–468CrossRefGoogle Scholar
  12. 12.
    Epstein JI, Allsbrook WC Jr, Amin MB et al (2005) The 2005 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma. Am J Surg Pathol 29:1228–1242CrossRefPubMedGoogle Scholar
  13. 13.
    D’Amico AV, Whittington R, Malkowicz SB et al (1998) Biochemical outcomes after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 280:969–974CrossRefPubMedGoogle Scholar
  14. 14.
    Rubin DB, Thomas N (1996) Matching estimated propensity scores: relating theory to practice. Biometrics 52:249–264CrossRefPubMedGoogle Scholar
  15. 15.
    Sooriakumaran P, Nyberg T, Akre O et al (2014) Comparative effectiveness of radical prostatectomy and radiotherapy in prostate cancer: observational study of mortality outcomes. BMJ 348:g1502PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Boorjian SA, Karnes RJ, Viterbo R et al (2011) Long-term survival after radical prostatectomy versus external-beam radiotherapy for patients with high-risk prostate cancer. Cancer 117:2883–2891PubMedCentralCrossRefPubMedGoogle Scholar
  17. 17.
    Heidenreich A, Bastian PJ, Bellmunt J et al (2014) EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol 65:124–137CrossRefPubMedGoogle Scholar
  18. 18.
    Meng MV, Elkin EP, Latini DM et al (2005) Treatment of patients with high risk localized prostate cancer: results from cancer of the prostate strategic urological research endeavor (CaPSURE). J Urol 173:1557–1561CrossRefPubMedGoogle Scholar
  19. 19.
    Merio T, San Francisco IF, Rojas PA et al (2013) Itensity-modulated radiotherapy versus radical prostatectomy in patients with localized prostate cancer: long-term follow-up. BMC Cancer 13:530–538CrossRefGoogle Scholar
  20. 20.
    Ward JF, Slezak JM, Blute ML et al (2005) Radical prostatectomy for clinically advanced (cT3) prostate cancer since the advent of prostate-specific antigen testing: 15-year outcome. BJU Int 95:751–756CrossRefPubMedGoogle Scholar
  21. 21.
    Cooperberg MR, Vickers AJ, Broering JM et al (2010) Comparative risk-adjusted mortality outcomes after primary surgery, radiotherapy, or androgen-deprivation therapy for localized prostate cancer. Cancer 116:5226–5234PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Nepple KG, Stephenson AJ, Kallogjeri D et al (2013) Mortality after prostate cancer treatment with radical prostatectomy, external-beam radiation therapy, or brachytherapy in men without comorbidity. Eur Urol 64:372–378PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Gleave M, Kelly WK (2005) High-risk localized prostate cancer: a case for early chemotherapy. J Clin Oncol 23:8186–8191CrossRefPubMedGoogle Scholar
  24. 24.
    Vuky J, Porter C, Isacson C et al (2009) Phase II trial of neoadjuvant docetaxel and gefitinib followed by radical prostatectomy in patients with high-risk, locally advanced prostate cancer. Cancer 115:784–791CrossRefPubMedGoogle Scholar
  25. 25.
    Womble PR, VanVeldhuizen PJ, Nisbet AA et al (2011) A phase II clinical trial of neoadjuvant ketoconazole and docetaxel chemotherapy before radical prostatectomy in high risk patients. J Urol 186:882–887CrossRefPubMedGoogle Scholar
  26. 26.
    Taplin ME, Montgomery RB, Logothetis C et al (2012) Effect of neoadjuvant abiraterone acetate plus leuprolide acetate on PSA, pathological complete response (pCR), and near pCR in localized high-risk prostate cancer: results of a randomized phase II study. J Clin Oncol 30 (supple). (abstract 4521)Google Scholar
  27. 27.
    Lou DY, Fong L (2014) Neoadjuvant therapy for localized prostate cancer: examining mechanism of action and efficacy within tumor. Urol Oncol. doi:  10.1016/j.urolonc.2013.12.001. (in press)
  28. 28.
    Koie T, Yamamoto H, Hatakeyama S et al (2011) Minimum incision endoscopic radical prostatectomy: clinical and oncological outcomes at a single institute. Eur J Surg Oncol 37:805–810CrossRefPubMedGoogle Scholar
  29. 29.
    Van Poppel H, Werbrouck PW, Baert L (1990) Effect of estramustine phosphate on free androgens: a comparative study of the effect on orchiectomy and estramustine phosphate on free androgens in patients with prostatic cancer. Acta Urol Belg 58:89–95PubMedGoogle Scholar
  30. 30.
    Lawrentschuk N, Fernandes K, Bell D et al (2011) Efficacy of a second line luteinizing hormone-releasing hormone agonist after advanced prostate cancer biochemical recurrence. J Urol 185:848–854CrossRefPubMedGoogle Scholar
  31. 31.
    Kraus S, Noar Z, Seger R (2006) Gonodotropin-releasing hormone in apoptosis of prostate cancer cells. Cancer Lett 234:109–123CrossRefPubMedGoogle Scholar
  32. 32.
    Hoshi S, Yamaguchi O, Fujioka T et al (2006) A randomized comparative study of endocrine monotherapy and a combination of estramustine phosphate with the endocrine therapy in patients with untreated stage D prostate cancer. Int J Clin Oncol 11:303–308CrossRefPubMedGoogle Scholar

Copyright information

© Japan Society of Clinical Oncology 2015

Authors and Affiliations

  • Takuya Koie
    • 1
    Email author
  • Koji Mitsuzuka
    • 2
  • Takahiro Yoneyama
    • 1
  • Shintaro Narita
    • 3
  • Sadafumi Kawamura
    • 4
  • Yasuhiro Kaiho
    • 2
  • Norihiko Tsuchiya
    • 3
  • Tatsuo Tochigi
    • 4
  • Tomonori Habuchi
    • 3
  • Yoichi Arai
    • 2
  • Chikara Ohyama
    • 1
  • Tohru Yoneyama
    • 1
  • Yuki Tobisawa
    • 1
  1. 1.Department of UrologyHirosaki University Graduate School of MedicineHirosakiJapan
  2. 2.Department of UrologyTohoku University Graduate School of MedicineSendaiJapan
  3. 3.Department of UrologyAkita University Graduate School of MedicineAkitaJapan
  4. 4.Department of UrologyMiyagi Cancer CenterNatoriJapan

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