放疗联合或不联合抗雄激素疗法治疗复发性前列腺癌的比较研究 - NEJM医学前沿
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放疗联合或不联合抗雄激素疗法治疗复发性前列腺癌的比较研究
Radiation with or without Antiandrogen Therapy in Recurrent Prostate Cancer


William U. Shipley ... 肿瘤 • 2017.02.02
相关阅读
• 高危前列腺癌有无最优治疗方案 • 阿比特龙用于既往未经激素治疗的前列腺癌 • 转移性前列腺癌的联合治疗

放射治疗联合抗雄激素治疗已成为局部晚期和根治术后生化复发前列腺癌的主要治疗模式

 

郑磊,陈佳艺*

上海交通大学医学院附属瑞金医院放射治疗科

*通讯作者


在中高危局限期前列腺癌患者中,前列腺切除联合盆腔淋巴结清扫术目前被认为是标准根治性治疗手段之一,但仍有约1/3患者术后出现复发转移,其中绝大部分表现为生化复发(血清PSA水平升高而无影像或临床复发证据)。对于术后单纯生化复发、既往没有接受术后放疗的患者,目前治疗的争议集中在单纯挽救性外照射还是需要联合抗雄激素治疗。

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摘要


背景

接受了根治性前列腺切除术以及有前列腺癌复发证据(以前列腺特异性抗原[PSA]持续或再次升高信号)的男性,通常必须接受挽救性放射治疗(以下简称放疗)。但我们尚不知晓抗雄激素疗法联合放疗能否进一步改善肿瘤的控制并延长总生存期。


方法

在这项从1998年至2003年间实施的双盲、安慰剂对照临床试验中,我们分配760例符合入选条件的患者在放疗期间以及放疗结束后接受放疗加抗雄激素疗法(比卡鲁胺每日150 mg,共24个月)或每日服用安慰剂片。患者的入组条件为:接受了前列腺切除术联合淋巴结切除术,并且经病理学检测评估肿瘤分期为T2(肿瘤局限于前列腺,但手术切缘阳性)或T3(组织学扩展至前列腺囊外),无淋巴结受累, PSA为0.2~0.4 ng/mL的可检出水平。主要终点为总生存率。


结果

生存患者的中位随访时间为13年。在第12年时,保险精算总生存率在比卡鲁胺组为76.3%,相比安慰剂组为71.3%(死亡的风险比为0.77;95%置信区间为0.59~0.99;P=0.04)。采用集中复审的方法评估的12-年前列腺癌死亡率,比卡鲁胺组为5.8%,相比安慰剂组为13.4%(P<0.001)。在第12年时,比卡鲁胺组中前列腺癌转移的累计发生率为14.5%,相比安慰剂组为23.0%(P=0.005)。两组间与放疗相关的晚期不良事件发生率相似。比卡鲁胺组有69.7%的患者记录有男性乳腺发育,相比安慰剂组为10.9%(P<0.001)。


结论

与放疗加安慰剂相比,在挽救性放疗基础上加用24个月的每日比卡鲁胺抗雄激素疗法可以显著提高长期总生存率,并降低转移性前列腺癌发生率以及前列腺癌死亡率(由美国国立癌症研究所[National Cancer Institute]和阿斯利康[AstraZeneca]公司资助;RTOG 9601 在ClinicalTrials.gov注册号为NCT00002874)。





作者信息

William U. Shipley, M.D., Wendy Seiferheld, M.S., Himanshu R. Lukka, M.D., Pierre P. Major, M.D., Niall M. Heney, M.D., David J. Grignon, M.D., Oliver Sartor, M.D., Maltibehn P. Patel, M.D., Jean-Paul Bahary, M.D., Anthony L. Zietman, M.D., Thomas M. Pisansky, M.D., Kenneth L. Zeitzer, M.D., Colleen A.F. Lawton, M.D., Felix Y. Feng, M.D., Richard D. Lovett, M.D., Alexander G. Balogh, M.D., Luis Souhami, M.D., Seth A. Rosenthal, M.D., Kevin J. Kerlin, M.D., James J. Dignam, Ph.D., Stephanie L. Pugh, Ph.D., and Howard M. Sandler, M.D., for the NRG Oncology RTOG*
From Massachusetts General Hospital and Harvard Medical School, Boston (W.U.S., N.M.H., A.L.Z.); NRG Oncology Statistics and Data Management Center (W.S., J.J.D., S.L.P.) and Einstein Medical Center (K.L.Z.), Philadelphia; Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, ON (H.R.L., P.P.M., M.P.P.), Hospital Notre-Dame du Centre Hospitalier de l’Université de Montréal (J.-P.B.) and McGill University Health Centre (L.S.), Montreal, and Tom Baker Cancer Centre, Calgary, AB (A.G.B.) — all in Canada; Indiana University, Indianapolis (D.J.G.); Tulane University, New Orleans (O.S.); Mayo Clinic, Rochester, MN (T.M.P.); Medical College of Wisconsin, Milwaukee (C.A.F.L.); University of Michigan, Ann Arbor (F.Y.F.); University of Vermont Medical Center, Burlington (R.D.L.); Radiation Oncology Center, Sacramento (S.A.R.), and Cedars–Sinai Medical Center, Los Angeles (H.M.S.) — both in California; Wayne Radiation Oncology, Goldsboro, NC (K.J.K.); and the University of Chicago, Chicago (J.J.D.). Address reprint requests to Dr. Shipley at the Department of Radiation Oncology, Massachusetts General Hospital, 55 Fruit St., Cox 3, Boston, MA 02114, or at wshipley@partners.org. *A complete list of the investigators in the NRG Oncology Radiation Therapy Oncology Group (RTOG) is provided in the Supplementary Appendix, available at NEJM.org.

 

参考文献

1. Cooperberg MR, Carroll PR. Trends in management for patients with localized prostate cancer, 1990-2013. JAMA 2015;314:80-82

2. Wilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med 2012;367:203-213

3. Mullins JK, Feng Z, Trock BJ, Epstein JI, Walsh PC, Loeb S. The impact of anatomical radical retropubic prostatectomy on cancer control: the 30-year anniversary. J Urol 2012;188:2219-2224

4. Trock BJ, Han M, Freedland SJ, et al. Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy. JAMA 2008;299:2760-2769

5. Stephenson AJ, Scardino PT, Kattan MW, et al. Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy. J Clin Oncol 2007;25:2035-2041

6. Pisansky TM, Kozelsky TF, Myers RP, et al. Radiotherapy for isolated serum prostate specific antigen elevation after prostatectomy for prostate cancer. J Urol 2000;163:845-850

7. Valcenti RK, Thompson I, Albertson P, et al. Adjuvant and salvage radiation therapy after prostatectomy: American Society for Radiation Oncology/American Urological Association guidelines. Int J Radiat Oncol Biol Phys 2013;86:822-828

8. Pilepich MV, Caplan R, Byhardt RW, et al. Phase III trial of androgen suppression using goserelin in unfavorable-prognosis carcinoma of the prostate treated with definitive radiotherapy: report of Radiation Therapy Oncology Group Protocol 85-31. J Clin Oncol 1997;15:1013-1021

9. Bolla M, Gonzalez D, Warde P, et al. Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med 1997;337:295-300

10. 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;21:3972-3978

11. Iversen P, Tyrrell CJ, Kaisary AV, et al. Casodex (bicalutamide) 150-mg monotherapy compared with castration in patients with previously untreated nonmetastatic prostate cancer: results from two multicenter randomized trials at a median follow-up of 4 years. Urology 1998;51:389-396

12. Tyrrell CJ, Kaisary AV, Iversen P, et al. A randomised comparison of ‘Casodex’ (bicalutamide) 150 mg monotherapy versus castration in the treatment of metastatic and locally advanced prostate cancer. Eur Urol 1998;33:447-456

13. Shipley WU, Hunt D, Lukka HR, et al. Initial report of RTOG 9601, a phase III trial in prostate cancer: effect of anti-androgen therapy (AAT) with bicalutamide during and after radiation therapy (RT) on freedom from progression and incidence of metastatic disease in patients following radical prostatectomy (RP) with pT2-3,N0 disease and elevated PSA levels. J Clin Oncol 2011;29:Suppl:7. abstract.

14.  American Joint Commission on Cancer. AJCC cancer staging manual. 5th ed. Philadelphia: Lippincott-Raven, 1997.

15.  Zelen M. The randomization and stratification of patients to clinical trials. J Chronic Dis 1974;27:365-375

16. 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;31:1341-1346

17. DeMets DL, Lan KK. Interim analysis: the alpha spending function approach. Stat Med 1994;13:1341-1356

18. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-481

19. Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 1966;50:163-170

20. Cox DR.. Regression models and life-tables. J R Stat Soc [B] 1972;34:187-220

21. Gaynor JJ, Feuer EJ, Tan CC, et al. On the use of cause-specific failure and conditional failure probabilities: examples from clinical oncology data. J Am Stat Assoc 1993;88:400-409

22. Gray RJ. A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1988;16:1141-1154

23. Laupacis A, Sackett DL, Roberts RS. An assessment of clinically useful measures of the consequences of treatment. N Engl J Med 1988;318:1728-1733

24. Altman DG, Andersen PK. Calculating the number needed to treat for trials where the outcome is time to an event. BMJ 1999;319:1492-1495

25. Efstathiou JA, Bae K, Shipley WU, et al. Cardiovascular mortality and duration of androgen deprivation for locally advanced prostate cancer: analysis of RTOG 92-02. Eur Urol 2008;54:816-823

26. Efstathiou JA, Bae K, Shipley WU, et al. Cardiovascular mortality after androgen deprivation therapy for locally advanced prostate cancer: RTOG 85-31. J Clin Oncol 2009;27:92-99

27. Voog JC, Paulus R, Shipley WU, et al. Cardiovascular mortality following short-term androgen deprivation in clinically localized prostate cancer: an analysis of RTOG 94-08. Eur Urol 2016;69:204-210

28. Wirth MP, See WA, McLeod DG, Iversen P, Morris T, Carroll K. 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. J Urol 2004;172:1865-1870

29. Parker C, Clarke N, Logue J, et al. RADICALS (Radiotherapy and Androgen Deprivation in Combination after Local Surgery). Clin Oncol 2007;19:167-171

30. Carrie C, Hasbini A, De Laroche G, et al. Interest of short hormonotherapy associated with radiotherapy as salvage treatment for biological relapse after radical prostatectomy: results of the GETUG-AFU 16 phase III randomized trial. J Clin Oncol 2015;33:Suppl:5006. abstract.

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