Annals of Surgical Oncology

, Volume 26, Issue 1, pp 297–305 | Cite as

Neoadjuvant Androgen Deprivation Therapy Prior to Radical Prostatectomy: Recent Trends in Utilization and Association with Postoperative Surgical Margin Status

  • Tyler R. McClintock
  • Nicolas von Landenberg
  • Alexander P. Cole
  • Stuart R. Lipsitz
  • Philipp Gild
  • Maxine Sun
  • Sean A. Fletcher
  • Florian Roghmann
  • Mani Menon
  • Paul L. Nguyen
  • Joachim Noldus
  • Toni K. Choueiri
  • Adam S. Kibel
  • Quoc-Dien TrinhEmail author
Urologic Oncology



In this study, we sought to describe the contemporary trends in utilization of neoadjuvant androgen deprivation therapy (ADT). As a secondary endpoint, we assessed the community-level effect of neoadjuvant ADT on positive surgical margins after radical prostatectomy (RP).


Using the National Cancer Database (2004–2014), we identified patients with clinically localized prostate cancer (PCa) [cT1-4N0M0] treated with RP. The estimated annual percentage change (EAPC) mixed linear regression methodology was used for temporal trend analysis of neoadjuvant ADT. Observed differences in baseline characteristics between patients treated with neoadjuvant ADT versus those who were not were then controlled for using an inverse probability of treatment weighting (IPTW) approach. IPTW-adjusted analyses were then performed to examine the odds of positive surgical margins.


Overall, 8184 (2.12%) and 377,843 (97.88%) individuals with PCa were treated with neoadjuvant ADT prior to RP versus RP only, respectively. There was a consistent trend in decreasing use of neoadjuvant ADT over time, with a nadir observed in 2011 [EAPC − 8.08; 95% confidence interval (CI) − 11.7 to − 4.32; p < 0.05]. In IPTW-adjusted analyses, the odds of positive surgical margins were lower in patients receiving neoadjuvant ADT with low-risk [odds ratio (OR) 0.65; 95% CI 0.51–0.84; p < 0.001] and intermediate-risk [OR 0.76; 95% CI 0.69–0.85; p < 0.001] PCa.


After a period of steady decline, there appears to be a modest trend towards increased utilization of neoadjuvant ADT in more recent years. We found an association between neoadjuvant ADT and decreased odds of positive surgical margins among low- and intermediate-risk patients.



Quoc-Dien Trinh is supported by the Brigham Research Institute Fund to Sustain Research Excellence, the Bruce A. Beal and Robert L. Beal Surgical Fellowship, the Genentech Bio-Oncology Career Development Award from the Conquer Cancer Foundation of the American Society of Clinical Oncology (Grant No. 10202), a Health Services Research pilot test grant from the Defense Health Agency, the Clay Hamlin Young Investigator Award from the Prostate Cancer Foundation (Grant No. 16YOUN20), and an unrestricted educational Grant from the Vattikuti Urology Institute.


Quoc-Dien Trinh reports consulting fees from Bayer and Astellas. Adam S. Kibel reports consulting fees from Profound, Janssen and ConfirmMDX. Tyler R. McClintock, Nicolas von Landenberg, Alexander P. Cole, Stuart R. Lipsitz, Philipp Gild, Maxine Sun, Sean A. Fletcher, Florian Roghmann, Mani Menon, Paul L. Nguyen, Joachim Noldus, and Toni K. Choueiri have no conflicts of interest to declare.


  1. 1.
    Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016;66(4):271–289.CrossRefGoogle Scholar
  2. 2.
    Gunner C, Gulamhusein A, Rosario DJ. The modern role of androgen deprivation therapy in the management of localised and locally advanced prostate cancer. J Clin Urol. 2016;9(2 Suppl):24–29.CrossRefGoogle Scholar
  3. 3.
    Aus G, Abrahamsson PA, Ahlgren G, Hugosson J, Lundberg S, Schain M, et al. Three‐month neoadjuvant hormonal therapy before radical prostatectomy: a 7‐year follow‐up of a randomized controlled trial. BJU Int. 2002;90(6):561–566.CrossRefGoogle Scholar
  4. 4.
    Van Poppel H, De Ridder D, Elgamal AA, Van de Voorde W, Werbrouck P, Ackaert K, et al. Neoadjuvant hormonal therapy before radical prostatectomy decreases the number of positive surgical margins in stage T2 prostate cancer: interim results of a prospective randomized trial. J Urol. 1995;154(2):429–434.CrossRefGoogle Scholar
  5. 5.
    Soloway MS, Pareek K, Sharifi R, Wajsman Z, McLeod D, Wood DP, et al. Neoadjuvant androgen ablation before radical prostatectomy in cT2bNxMo prostate cancer: 5-year results. J Urol. 2002;167(1):112–116.CrossRefGoogle Scholar
  6. 6.
    Nguyen PL, Alibhai SM, Basaria S, D’Amico AV, Kantoff PW, Keating NL, et al. Adverse effects of androgen deprivation therapy and strategies to mitigate them. Eur Urol. 2015;67(5):825–836.CrossRefGoogle Scholar
  7. 7.
    Meyer F, Bairati I, Bédard C, Lacombe L, Têtu B, Fradet Y. Duration of neoadjuvant androgen deprivation therapy before radical prostatectomy and disease-free survival in men with prostate cancer. Urology. 2001;58(2 Suppl 1):71–77.CrossRefGoogle Scholar
  8. 8.
    Sanda MG, Cadeddu JA, Kirkby E, Chen RC, Crispino T, Fontanarosa J, et al. Clinically localized prostate cancer: AUA/ASTRO/SUO Guideline. Part II: Recommended approaches and details of specific care options. J Urol. 2018;199(4):990–997.CrossRefGoogle Scholar
  9. 9.
    Shahinian VB, Kuo YF, Gilbert SM. Reimbursement policy and androgen-deprivation therapy for prostate cancer. N Engl J Med. 2010;363(19):1822–1832.CrossRefGoogle Scholar
  10. 10.
    Weight CJ, Klein EA, Jones JS. Androgen deprivation falls as orchiectomy rates rise after changes in reimbursement in the U.S. Medicare population. Cancer. 2008;112(10):2195–2201.CrossRefGoogle Scholar
  11. 11.
    Shahinian VB, Kuo YF. Reimbursement cuts and changes in urologist use of androgen deprivation therapy for prostate cancer. BMC Urol. 2015;15:25.CrossRefGoogle Scholar
  12. 12.
    Montgomery B, Tretiakova MS, Joshua AM, Gleave ME, Fleshner N, Bubley GJ, et al. Neoadjuvant enzalutamide prior to prostatectomy. Clin Cancer Res. 2017;23(9):2169–2176.CrossRefGoogle Scholar
  13. 13.
    US National Institutes of Health. 2017. Scholar
  14. 14.
    Tosco L, Laenen A, Briganti A, Gontero P, Karnes RJ, Albersen M, et al. The survival impact of neoadjuvant hormonal therapy before radical prostatectomy for treatment of high-risk prostate cancer. Prostate Cancer Prostatic Dis. 2017;20(4):407–412.CrossRefGoogle Scholar
  15. 15.
    Winchester DP, Stewart AK, Bura C, Jones RS. The National Cancer Data Base: a clinical surveillance and quality improvement tool. J Surg Oncol. 2004;85(1):1–3.CrossRefGoogle Scholar
  16. 16.
    Fay MP, Tiwari RC, Feuer EJ, Zou Z. Estimating average annual percent change for disease rates without assuming constant change. Biometrics. 2006;62(3):847–854.CrossRefGoogle Scholar
  17. 17.
    Lemeshow S, Hosmer DW Jr. A review of goodness of fit statistics for use in the development of logistic regression models. Am J Epidemiol. 1982;115(1):92–106.CrossRefGoogle Scholar
  18. 18.
    Austin PC. The use of propensity score methods with survival or time-to-event outcomes: reporting measures of effect similar to those used in randomized experiments. Stat Med. 2014;33(7):1242–1258.CrossRefGoogle Scholar
  19. 19.
    Austin PC. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med. 2009;28(25):3083–3107.CrossRefGoogle Scholar
  20. 20.
    Cole SR, Hernan MA. Adjusted survival curves with inverse probability weights. Comput Methods Programs Biomed. 2004;75(1):45–49.CrossRefGoogle Scholar
  21. 21.
    Grambsch PM, Therneau T. Proportional hazards tests and diagnostics based on weighted residuals. Biometrika, 1994;81(3):515–526.CrossRefGoogle Scholar
  22. 22.
    Chang SL, Liao JC, Shinghal R. Decreasing use of luteinizing hormone-releasing hormone agonists in the United States is Independent of Reimbursement Changes: A Medicare and Veterans Health Administration claims analysis. J Urol. 2009;182(1):255–260; discussion 261.Google Scholar
  23. 23.
    Strum SB, McDermed JE, Scholz MC, Johnson H, Tisman G. Anaemia associated with androgen deprivation in patients with prostate cancer receiving combined hormone blockade. Br J Urol. 1997;79(6):933–941.CrossRefGoogle Scholar
  24. 24.
    Maillefert JF, Sibilia J, Michel F, Saussine C, Javier RM, Tavernier C. Bone mineral density in men treated with synthetic gonadotropin-releasing hormone agonists for prostatic carcinoma. J Urol. 1999;161(4):1219–1222.CrossRefGoogle Scholar
  25. 25.
    Shahinian VB, Kuo YF, Freeman JL, Goodwin JS. Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med. 2005;352(2):154–164.CrossRefGoogle Scholar
  26. 26.
    Herr HW, O’Sullivan M. Quality of life of asymptomatic men with nonmetastatic prostate cancer on androgen deprivation therapy. J Urol. 2000;163(6):1743–1746.CrossRefGoogle Scholar
  27. 27.
    D’Amico AV, Denham JW, Crook J, Chen MH, Goldhaber SZ, Lamb DS. Influence of androgen suppression therapy for prostate cancer on the frequency and timing of fatal myocardial infarctions. J Clin Oncol. 2007;25(17):2420–2425.CrossRefGoogle Scholar
  28. 28.
    McKay RR, Choueiri TK, Taplin ME. Rationale for and review of neoadjuvant therapy prior to radical prostatectomy for patients with high-risk prostate cancer. Drugs. 2013;73(13):1417–1430.CrossRefGoogle Scholar
  29. 29.
    Grossfeld GD, Chang JJ, Broering JM, Miller DP, Yu J, Flanders SC, Henning JM. Impact of positive surgical margins on prostate cancer recurrence and the use of secondary cancer treatment: data from the CaPSURE database. J Urol. 2000;163(4):1171–1177; quiz 1295.Google Scholar
  30. 30.
    Alkhateeb S, Alibhai S, Fleshner N, Finelli A, Jewett M, Zlotta A, et al. Impact of positive surgical margins after radical prostatectomy differs by disease risk group. J Urol. 2010;183(1):145–150.CrossRefGoogle Scholar
  31. 31.
    Shelley MD, Kumar S, Wilt T, Staffurth J, Coles B, Mason MD. A systematic review and meta-analysis of randomised trials of neo-adjuvant hormone therapy for localised and locally advanced prostate carcinoma. Cancer Treat Rev. 2009;35(1):9–17.CrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2018

Authors and Affiliations

  • Tyler R. McClintock
    • 1
  • Nicolas von Landenberg
    • 1
    • 2
  • Alexander P. Cole
    • 1
  • Stuart R. Lipsitz
    • 3
  • Philipp Gild
    • 1
    • 4
  • Maxine Sun
    • 5
  • Sean A. Fletcher
    • 3
  • Florian Roghmann
    • 1
  • Mani Menon
    • 6
  • Paul L. Nguyen
    • 5
  • Joachim Noldus
    • 1
  • Toni K. Choueiri
    • 5
  • Adam S. Kibel
    • 1
    • 5
  • Quoc-Dien Trinh
    • 5
    Email author
  1. 1.Division of Urology, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  2. 2.Department of UrologyRuhr-University Bochum, Marien Hospital HerneHerneGermany
  3. 3.Center for Surgery and Public Health, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  4. 4.Department of UrologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  5. 5.Dana-Farber/Brigham and Women’s Hospital Cancer CenterHarvard Medical SchoolBostonUSA
  6. 6.Vattikuti Urology Institute, Vattikuti Urology Institute (VUI) Center for Outcomes Research Analytics and EvaluationHenry Ford HospitalDetroitUSA

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