Abstract
Background:
The optimal hormone treatment strategy in prostate cancer is uncertain, particularly in patients with metastatic disease. We aimed to compare the relative benefits and harms of intermittent androgen deprivation (IAD) to continuous androgen deprivation (CAD) in all stages of prostate cancer.
Methods:
We included eight randomised control trials (4668 patients) in our systematic review and meta-analysis. Median follow-up ranged from 29 to 118 months. Pooled hazard ratios (HRs) were calculated for overall survival (OS), cancer-specific survival, time to cancer progression and mortality unrelated to prostate cancer. The relative effect of treatment in patients with metastatic and those with non-metastatic disease was compared using pre-planned subgroup analysis.
Results:
There was no difference in OS between patients treated with IAD and CAD (HR 1.01, 95% confidence interval (CI) 0.93–1.10); nor was there any difference in cancer-specific survival (HR 1.03; 95% CI 0.88–1.21). There was a non-significant trend towards longer time to prostate cancer progression for IAD (HR 0.93, 95% CI 0.84–1.04), raising the possibility of slower selection for castrate resistance. There was no significant difference in OS when analysis was restricted to patients with metastatic disease (HR 1.04, 95% CI 0.91–1.19) or patients without metastatic disease (HR 1.06, 95% CI 0.91–1.23) (test for subgroup differences P=0.84). Most studies found an improvement in quality of life or toxicity profile with IAD.
Conclusions:
IAD is non-inferior to CAD in terms of OS and cancer-specific survival, and is at least non-inferior in terms of time to progression. This meta-analysis confirms IAD as a valid standard of care for managing prostate cancer patients.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 4 print issues and online access
$259.00 per year
only $64.75 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Australian Institute of Health and Welfare (AIHW). ACIM (Australian Cancer Incidence and Mortality) 2012.
Loblaw DA, Virgo KS, Nam R, Somerfield MR, Ben-Josef E, Mendelson DS et al. Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer-2007 update of an ASCO practice guideline. J Clin Oncol 2007; 25: 1596–1605.
Strum S, Scholz M, McDermed J . The androgen deprivation syndrome: the incidence and severity in prostate cancer. Proc Am Soc Clin Oncol 1998; 17: 316.
Klotz L, Herr H, Morse M, Whitmore W . Intermittent endocrine therapy for advanced prostate cancer. Cancer 1986; 58: 2546–2550.
Bruchovsky N, Rennie P, Coldman A, Goldenberg S, To M, Lawson D . Effects of androgen withdrawal on the stem cell composition of the Shionogi carcinoma. Cancer Res 1990; 50: 2275–2282.
Abrahamsson PA . Potential benefits of intermittent androgen suppression therapy in the treatment of prostate cancer: a systematic review of the literature. Eur Urol 2010; 57: 49–59.
Conti PD, Atallah AN, Arruda H, Soares BG, El Dib RP, Wilt TJ . Intermittent versus continuous androgen suppression for prostatic cancer. Cochrane Database Syst Rev 2007; 4: CD005009.
Niraula S, Le LW, Tannock IF . Treatment of prostate cancer with intermittent versus continuous androgen deprivation: a systematic review of randomized trials. J Clin Oncol 2013; 31: 2029–2036.
Hussain M, Tangen CM, Berry DL, Higano CS, Crawford ED, Liu G et al. Intermittent versus continuous androgen deprivation in prostate cancer. N Engl J Med 2013; 368: 1314–1325.
Calais da Silva FE, Bono AV, Whelan P, Brausi M, Marques Queimadelos A, Martin JA et al. Intermittent androgen deprivation for locally advanced and metastatic prostate cancer: results from a randomised phase 3 study of the South European Uroncological Group. Eur Urol 2009; 55: 1269–1277.
Mottet N, Van Damme J, Loulidi S, Russel C, Leitenberger A, Wolff JM et al. Intermittent hormonal therapy in the treatment of metastatic prostate cancer: a randomized trial. BJU Int 2012; 110: 1262–1269.
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009; 46: 339.
Higgins J, Green S . Cochrane Handbook for Systematic Reviews of Interventions 5.1.0. The Cochrane Library 2011.
Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR . Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 2007; 6: 16.
Schasfoort E, Heathcote P, Lock M, Zerbib M, Newling D . Androgen suppression of advanced prostate cancer: intermittent or continuous therapy [abstract]. Eur J Cancer 2001; 37 (Suppl 6): S218.
Calais da Silva F, Bono A, Whelan P, Brausi M, Queimadelos M, Portillo J et al. Intermittent androgen deprivation for locally advanced prostate cancer. Preliminary experience from an ongoing randomized controlled study of the South European urooncological group. Oncology 2003; 65 (Suppl 1): 24–28.
Tunn U, Kurek R, Keinle E . Intermittent is as effective as continuous androgen deprivation in patients with PSA relapse after radical prostatectomy. J Urol 2004; 171 (abstract 1458): 384.
Langenhuijsen J, Badhauser D, Schaaf B, Kiemeney L, Witjes A, Mulders P . Continuous vs. intermittent androgen deprivation therapy for metastatic prostate cancer. Urol Oncol 2013; 31: 549–556.
Dutkiewicz S . Comparison of maximal and more maximal intermittent androgen blockade during 5-year treatment of advanced prostate cancer T3NxMx-1. Int Urol Nephrol 2012; 44: 487–492.
Berthelet E, Pickles T, Truong PT, Liu M, Pai HH, Kwan WB et al. What is the optimal duration of androgen deprivation therapy in prostate cancer patients presenting with prostate-specific antigen levels>20 ng/ml? CanJ Urol 2007; 14: 3621–3627.
Organ M, Wood L, Wilke D, Skedgel C, Cheng T, North S et al. Intermittent LHRH therapy in the management of castrate-resistant prostate cancer (crpca) results of a multi-institutional randomized prospective clinical trial. Am J Clin Oncol 2012; 36: 601–605.
Salonen AJ, Taari K, Ala-Opas M, Viitanen J, Lundstedt S, Tammela TLJ . The FinnProstate Study VII: intermittent versus continuous androgen deprivation in patients with advanced prostate cancer. J Urol 2012; 187: 2074–2081.
Crook JM, O'Callaghan CJ, Duncan G, Dearnaley DP, Higano CS, Horwitz EM et al. Intermittent androgen suppression for rising PSA level after radiotherapy. N Engl J Med 2012; 367: 895–903.
de Leval J, Boca P, Yousef E, Nicolas H, Jeukenne M, Seidel L et al. Intermittent versus continuous total androgen blockade in the treatment of patients with advanced hormone naïve prostate cancer: results of a prospective randomized. Clin Prostate Cancer 2002; 1: 163–171.
Irani J, Celhay O, Hubert J, Bladou F, Ragni E, Trape G et al. Continuous versus six months a year maximal androgen blockade in the management of prostate cancer: a randomised study. Eur Urol 2008; 54: 382–391.
Langenhuijsen JF, Schasfoort EMC, Heathcote P, Lock MTWT, Zerbib M, Dijkema HE et al. Intermittent androgen suppression in patients with advanced prostate cancer: an update of the TULP survival data. Eur Urol 2008; 7: 205.
Tunn UW, Canepa G, Kochanowsky A, Kienle E . Testosterone recovery in the off-treatment time in prostate cancer patients undergoing intermittent androgen deprivation therapy. Prostate Cancer Prostatic Dis 2012; 15: 296–302.
Yamanaka H, Ito K, Naito S, Usami M, Fujimoto H, Matsuoka N et al. Effectiveness of adjuvant intermittent endocrine therapy following neoadjuvant endocrine therapy and external beam radiation therapy in men with locally advanced prostate cancer. Prostate 2005; 63: 56–64.
Miller K, Steiner U, Lingnau A . Randomised prospective study of intermittent versus continuous androgen suppression in advanced prostate cancer (abstract #5015). J Clin Oncol 2007; 25 (Suppl): 5015.
Hering F, Rodrigues PRT, Aurelio Lipay M, Nesrallah L, Srougi M . Metastatic adenocarcinoma of the prostate: comparison between continuous and intermittent hormonal treatment. Braz J Urol 2000; 26: 276–282.
Verhagen PC, Wissenburg MF, Wildhagen WA, Bolle AM, Verkerk FH, Schröder CH et al. Quality of life effects of intermittent and continuous hormonal therapy by cyproterone acetate (CPA) for metastatic prostate cancer. Eur Urol Supp 2008; 7: 206.
Salonen AJ, Ala-Opas KTM, Viitanen J, Lundstedt S, Tammela TLJ . Advanced Prostate Cancer Treated with Intermittent or Continuous Androgen Deprivation in the Randomised FinnProstate Study VII: Quality of Life and Adverse Effects. Eur Urol 2013; 63: 111–120.
Acknowledgements
RJE acknowledges research support from St Vincent’s Clinic Foundation.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Additional information
Supplementary Information accompanies the paper on the Prostate Cancer and Prostatic Diseases website
Supplementary information
Rights and permissions
About this article
Cite this article
Brungs, D., Chen, J., Masson, P. et al. Intermittent androgen deprivation is a rational standard-of-care treatment for all stages of progressive prostate cancer: results from a systematic review and meta-analysis. Prostate Cancer Prostatic Dis 17, 105–111 (2014). https://doi.org/10.1038/pcan.2014.10
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/pcan.2014.10
This article is cited by
-
Intermittent versus continuous androgen deprivation therapy for advanced prostate cancer
Nature Reviews Urology (2020)
-
Clinical significance of androgen secretion disorders in men with a malignancy
Medical Oncology (2017)
-
An Update on Triptorelin: Current Thinking on Androgen Deprivation Therapy for Prostate Cancer
Advances in Therapy (2016)