Hormonal Therapy plus Radiotherapy for Prostate Cancer in Different Treatment Courses: A Meta-Analysis_Chinese Journal of Evidence-Based Medicine

Authors：

ZHOU Zhirui ¹ ,  ZHU Xiaodong ¹ , LIANG Zhongguo ¹ , PAN Wenyan ²

1. Department of Radiation Oncology, Cancer Hospital of Guangxi Medical University, Nanning 530021, China;2. General Hospital of Ningxia Medical University, Yinchuan 750004, China;

Corresponding author：

ZHU Xiaodong, Email: zhuxdonggxmu@yahoo.cn

Keywords：

Prostate cancer; Radiotherapy; Hormonal therapy; Meta-analysis; Systematic review; Randomized controlled trial

DOI：

10.7507/1672-2531.20120186

Video：

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Objective 　To systematically review the effectiveness and safety of radiotherapy combined with short-term or long-term hormonal therapy for prostate cancer.
Methods 　Databases including EMbase, PubMed, Web of Science, CENTRAL and CBM were searched from inception to August 2012 to collect the randomized controlled trials (RCTs) on radiotherapy combined with short-term or long-term hormonal therapy for prostate cancer. According to the inclusion and exclusion criteria, data of the included studies were extracted, and the methodological quality was evaluated. Then meta-analysis was performed using RevMan 5.1, and the evidence qualities and recommendation levels were determined according to the GRADE System.
Results 　A total of 6 RCTs involving 3157 patients were included. The results of meta-analysis showed that there were no significant differences in the overall survival rate (RR=0.95, 95%CI 0.91 to 1.00) and the disease-free survival rate (RR=0.73, 95%CI 0.46 to 1.13) between the radiotherapy plus short-term hormonal therapy group (the short-term group) and the radiotherapy plus long-term hormonal therapy group (the long-term group). The long-term group was superior to the short-term group in biochemical failure-free survival rate (RR=0.81, 95%CI 0.68 to 0.97), clinical progression rate (RR=1.61, 95%CI 1.44 to 1.80), and prostate cancer-specific mortality (RR=1.44, 95%CI 1.16 to 1.80). Based on the GRADE system, the evidence level of biochemical failure-free survival was moderate with a weak recommendation; the evidence level of disease-free survival was low with a weak recommendation; the evidence level of overall survival was high with a weak recommendation; and the evidence levels of clinical progression rate and prostate cancer-specific mortality were high with a b recommendation.
Conclusion 　Currently, the limited evidence shows extending the length of hormone therapy is beneficial for patients with localized prostate cancer and locally advanced prostate cancer, especially for patients with high Gleason score, but it cannot raise overall survival rate and disease-free survival rate. This conclusion still needs to be further proved by more high-quality and large-scale RCTs.

Citation： ZHOU Zhirui,ZHU Xiaodong,LIANG Zhongguo,PAN Wenyan. Hormonal Therapy plus Radiotherapy for Prostate Cancer in Different Treatment Courses: A Meta-Analysis. Chinese Journal of Evidence-Based Medicine, 2012, 12(10): 1195-1202. doi: 10.7507/1672-2531.20120186 Copy

1.	Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. Ca-A Cancer Journal for Clinicians, 2005, 55(2): 74-108.
2.	Gronberg H. Prostate cancer epidemiology. Lancet, 2003, 361(9360): 859-864.
3.	Kumar S, Shelley M, Harrison C, et al. Neo-adjuvant and adjuvant hormone therapy for localised and locally advanced prostate cancer. Cochrane Database Syst Rev, 2006, 18(4): CD006019.
4.	Wirth MP, See WA, McLeod DG, et al. Bicalutamide 150 mg in addition to standard care in patients with localized or locally advanced prostate cancer: Results from the second analysis of the early prostate cancer program at median followup of 5.4 years. Journal of Urology, 2004, 172(5): 1865-1870.
5.	D’Amico AV, Denham JW, Bolla M, et al. Short- vs. long-term androgen suppression plus external beam radiation therapy and survival in men of advanced age with node-negative high-risk adenocarcinoma of the prostate. Cancer, 2007, 109(10): 2004-2010.
6.	Denham JW, Steigler A, Lamb DS, et al. Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial. In: The Lancet Oncology, 2005, 6(11): 841-850.
7.	Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from: www.cochrane-handbook.org.
8.	Balshem H, Helfanda M, Schunemann HJ, 等. GRADE指南: Ⅲ. 证据质量分级. 中国循证医学杂志, 2011, 11(4): 451-455.
9.	Guyatt GH, Oxman AD, Kunz R, 等. GRADE: 从证据到推荐. 中国循证医学杂志, 2009, 9(3): 257-259.
10.	Guyatt GH, Oxman AD, Vist GE, 等. GRADE: 证据质量和推荐强度分级的共识. 中国循证医学杂志, 2009, 9(1): 8-11.
11.	曾宪涛, 冷卫东, 李胜, 等. 如何正确理解及使用GRADE系统. 中国循证医学杂志, 2011, 11(9): 985-990.
12.	曾宪涛, 田国祥, 牛玉明, 等. GRADEprofiler软件的使用简介. 中国循证心血管医学杂志, 2011, 3(5): 390-392.
13.	Armstrong J, Taylor J, Thirion P, et al. Preliminary results of a randomised trial comparing short vs. protracted neoadjuvant hormonal therapy (NHT) prior to radiation therapy (RT) of localized prostate cancer. (Irish Clinical Oncology Research Group Protocol # 97-01). Radiotherapy and Oncology, 2004, 73(3): 78.
14.	Armstrong JG, Gillham CM, Dunne MT, et al. A Randomized Trial (Irish Clinical Oncology Research Group 97-01) Comparing Short Versus Protracted Neoadjuvant Hormonal Therapy Before Radiotherapy for Localized Prostate Cancer. Int J Radiat Oncol Biol Phys, 2010, 81(1): 35-45.
15.	Bolla M, De Reijke TM, Van Tienhoven G, et al. Duration of androgen suppression in the treatment of prostate cancer. New England Journal of Medicine, 2009, 360(24): 2516-2527.
16.	Crook J, Ludgate C, Malone S, et al. Report of a multicenter Canadian phase III randomized trial of 3 months vs. 8 months neoadjuvant androgen deprivation before standard-dose radiotherapy for clinically localized prostate cancer. In: International Journal of Radiation Oncology, Biology, Physics, 2004, 60(1): 15-23.
17.	Crook J, Ludgate C, Malone S, et al. Final report of multicenter Canadian Phase III randomized trial of 3 versus 8 months of neoadjuvant androgen deprivation therapy before conventional-dose radiotherapy for clinically localized prostate cancer. Int J Radiat Oncol Biol Phys, 2009, 73(2): 327-333.
18.	Denham JW, Steigler A, Lamb DS, et al. Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial. Lancet Oncol, 2011, 12(5): 451-459.
19.	Hanks GE, Pajak TF, Porter A, et al. Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: the Radiation Therapy Oncology Group Protocol 92-02. J Clin Oncol, 2003, 21(21): 3972-3978.
20.	Horwitz EM, Bae K, Hanks GE, et al. Ten-year follow-up of radiation therapy oncology group protocol 92-02: a phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer. J Clin Oncol, 2008, 26(15): 2497-2504.
21.	Lamb DS, Denham JW, Mameghan H, et al. Acceptability of short term neo-adjuvant androgen deprivation in patients with locally advanced prostate cancer. J of Euro Society for Therapeutic Radiology and Oncology, 2003, 68(3): 255-267.
22.	Laverdiere J, Nabid A, De Bedoya LD, et al. The efficacy and sequencing of a short course of androgen suppression on freedom from biochemical failure when administered with radiation therapy for T2-T3 prostate cancer. Journal of Urology, 2004, 171(3): 1137-1140.
23.	Zelefsky MJ. Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: Results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial. Urologic Oncology: Seminars and Original Investigations, 2006, 24(4): 376-377.
24.	Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys, 1995, 31(5): 1341-1346.
25.	Roach M, 3rd, Bae K, Speight J, et al. Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610. J Clin Oncol, 2008, 26(4): 585-591.
26.	Roach M, 3rd, DeSilvio M, Lawton C, et al. Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413. J Clin Oncol, 2003, 21(10): 1904-1911.

1. Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. Ca-A Cancer Journal for Clinicians, 2005, 55(2): 74-108.
2. Gronberg H. Prostate cancer epidemiology. Lancet, 2003, 361(9360): 859-864.
3. Kumar S, Shelley M, Harrison C, et al. Neo-adjuvant and adjuvant hormone therapy for localised and locally advanced prostate cancer. Cochrane Database Syst Rev, 2006, 18(4): CD006019.
4. Wirth MP, See WA, McLeod DG, et al. Bicalutamide 150 mg in addition to standard care in patients with localized or locally advanced prostate cancer: Results from the second analysis of the early prostate cancer program at median followup of 5.4 years. Journal of Urology, 2004, 172(5): 1865-1870.
5. D’Amico AV, Denham JW, Bolla M, et al. Short- vs. long-term androgen suppression plus external beam radiation therapy and survival in men of advanced age with node-negative high-risk adenocarcinoma of the prostate. Cancer, 2007, 109(10): 2004-2010.
6. Denham JW, Steigler A, Lamb DS, et al. Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial. In: The Lancet Oncology, 2005, 6(11): 841-850.
7. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from: www.cochrane-handbook.org.
8. Balshem H, Helfanda M, Schunemann HJ, 等. GRADE指南: Ⅲ. 证据质量分级. 中国循证医学杂志, 2011, 11(4): 451-455.
9. Guyatt GH, Oxman AD, Kunz R, 等. GRADE: 从证据到推荐. 中国循证医学杂志, 2009, 9(3): 257-259.
10. Guyatt GH, Oxman AD, Vist GE, 等. GRADE: 证据质量和推荐强度分级的共识. 中国循证医学杂志, 2009, 9(1): 8-11.
11. 曾宪涛, 冷卫东, 李胜, 等. 如何正确理解及使用GRADE系统. 中国循证医学杂志, 2011, 11(9): 985-990.
12. 曾宪涛, 田国祥, 牛玉明, 等. GRADEprofiler软件的使用简介. 中国循证心血管医学杂志, 2011, 3(5): 390-392.
13. Armstrong J, Taylor J, Thirion P, et al. Preliminary results of a randomised trial comparing short vs. protracted neoadjuvant hormonal therapy (NHT) prior to radiation therapy (RT) of localized prostate cancer. (Irish Clinical Oncology Research Group Protocol # 97-01). Radiotherapy and Oncology, 2004, 73(3): 78.
14. Armstrong JG, Gillham CM, Dunne MT, et al. A Randomized Trial (Irish Clinical Oncology Research Group 97-01) Comparing Short Versus Protracted Neoadjuvant Hormonal Therapy Before Radiotherapy for Localized Prostate Cancer. Int J Radiat Oncol Biol Phys, 2010, 81(1): 35-45.
15. Bolla M, De Reijke TM, Van Tienhoven G, et al. Duration of androgen suppression in the treatment of prostate cancer. New England Journal of Medicine, 2009, 360(24): 2516-2527.
16. Crook J, Ludgate C, Malone S, et al. Report of a multicenter Canadian phase III randomized trial of 3 months vs. 8 months neoadjuvant androgen deprivation before standard-dose radiotherapy for clinically localized prostate cancer. In: International Journal of Radiation Oncology, Biology, Physics, 2004, 60(1): 15-23.
17. Crook J, Ludgate C, Malone S, et al. Final report of multicenter Canadian Phase III randomized trial of 3 versus 8 months of neoadjuvant androgen deprivation therapy before conventional-dose radiotherapy for clinically localized prostate cancer. Int J Radiat Oncol Biol Phys, 2009, 73(2): 327-333.
18. Denham JW, Steigler A, Lamb DS, et al. Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial. Lancet Oncol, 2011, 12(5): 451-459.
19. Hanks GE, Pajak TF, Porter A, et al. Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: the Radiation Therapy Oncology Group Protocol 92-02. J Clin Oncol, 2003, 21(21): 3972-3978.
20. Horwitz EM, Bae K, Hanks GE, et al. Ten-year follow-up of radiation therapy oncology group protocol 92-02: a phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer. J Clin Oncol, 2008, 26(15): 2497-2504.
21. Lamb DS, Denham JW, Mameghan H, et al. Acceptability of short term neo-adjuvant androgen deprivation in patients with locally advanced prostate cancer. J of Euro Society for Therapeutic Radiology and Oncology, 2003, 68(3): 255-267.
22. Laverdiere J, Nabid A, De Bedoya LD, et al. The efficacy and sequencing of a short course of androgen suppression on freedom from biochemical failure when administered with radiation therapy for T2-T3 prostate cancer. Journal of Urology, 2004, 171(3): 1137-1140.
23. Zelefsky MJ. Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: Results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial. Urologic Oncology: Seminars and Original Investigations, 2006, 24(4): 376-377.
24. Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys, 1995, 31(5): 1341-1346.
25. Roach M, 3rd, Bae K, Speight J, et al. Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610. J Clin Oncol, 2008, 26(4): 585-591.
26. Roach M, 3rd, DeSilvio M, Lawton C, et al. Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413. J Clin Oncol, 2003, 21(10): 1904-1911.

Chinese Journal of Evidence-Based Medicine

Hormonal Therapy plus Radiotherapy for Prostate Cancer in Different Treatment Courses: A Meta-Analysis

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