Early versus deferred androgen suppression in the treatment of advanced prostatic cancer.
Early versus deferred androgen suppression in the treatment of advanced prostatic cancer.
复制标题
晚期前列腺癌治疗中的早期雄激素抑制与延迟雄激素抑制。
DOI：
--
复制
发表时间：
2001
影响因子：
8.4
通讯作者：
I. Rutks
中科院分区：
文献类型：
--
作者：
T. Wilt;B. Nair;R. MacDonald;I. Rutks
背景
前列腺癌是男性癌症死亡的主要原因。晚期前列腺癌患者的治疗目标包括延长生存期、预防或延迟疾病进展引起的症状、改善和维持生活质量、降低治疗相关的发病率。雄激素抑制治疗被认为是晚期前列腺癌男性患者的主要治疗方法。然而，目前尚不清楚与延迟至临床进展的体征和症状的雄激素抑制相比，对于局部晚期疾病或无症状转移的男性患者，早期雄激素抑制是否能改善生存时间和生活质量。
目标
本系统评价评估了早期与延期雄激素抑制治疗男性晚期前列腺癌的疗效和不良反应。
搜索策略
在一般和专业数据库（MEDLINE、EMBASE、CancerLIT、科克伦图书馆、VA科克伦前列腺疾病登记）中检索随机对照试验，并通过审查参考文献，包括蓝十字和蓝盾协会技术评价中心/医疗保健研究和质量局循证实践中心（BCBS/TEC-AHRQ）报告No.4的参考文献。
选择标准
所有已发表的随机试验均符合入选条件，前提是：将晚期前列腺癌男性随机分为早期和延迟雄激素抑制组;报告总体、无进展和癌症特异性生存期和/或不良事件;未使用雄激素抑制作为放射治疗的辅助治疗。
数据收集和分析
独立的评审员使用标准化表格提取关于试验特征、干预措施和结局的信息。审查结果的准确性，并通过讨论解决差异。比较有效性的主要结局指标是1年、2年、5年和10年的总生存率。还测量了无进展生存期、癌症特异性生存期、疾病进展引起的并发症和治疗不良反应的发生率。
主要结果
本次综述纳入了四项试验，涉及2，167例患者。所有试验均在使用前列腺特异性抗原（PSA）检测之前进行。关于所用治疗和开始治疗的要求，研究之间存在差异。早期治疗组的1、2、5和10年总生存率分别为88%、73%、44%和18%。延迟治疗组的总生存率分别为86%、71%、37%和12%。总生存率差异的汇总估计值支持早期治疗，但仅在10年时有显著性差异，此时仅有少数患者存活[OR = 1.16（95% CI：0.90 - 1.49），2年1.08（95% CI：0.89 - 1.33），5年1.19（95% CI：0.95 - 1.50），10年1.50（95% CI：1.04 - 2.16）]。前列腺癌特异性生存率的2年、5年和10年的汇总估计值支持早期治疗，尽管置信区间较宽，结果无统计学差异。2年、5年和10年的风险差异分别为2.7%、5.8%和4.6%。尽管每项研究都使用了独特的无进展生存期定义，但所有研究都发现早期干预组在所有时间点的无进展生存期均较好。仅在一项研究中报告了由于疾病进展导致的并发症，但在延迟治疗组中更常见。治疗引起的不良事件也仅在一项研究中报告，但在早期治疗组中发生频率更高。
评论者结论
来自随机对照试验的证据受到研究设计、癌症分期和入组受试者、所用干预措施、结局定义和报告的可变性以及缺乏用于诊断和监测目的的PSA检测的限制。然而，现有信息表明，早期雄激素抑制治疗晚期前列腺癌可减少疾病进展和进展引起的并发症。早期雄激素抑制可能会提供一个小的，但统计学显着改善总生存率在10年。前列腺癌特异性生存率无统计学显著差异，但不能排除具有临床意义的差异。这些结果需要评估的证据表明，更高的成本和更频繁的治疗相关的不良反应与早期治疗。需要更多的研究来更明确地评估早期与延迟雄激素抑制对前列腺癌患者的疗效和不良反应。特别是，试验应评估通过PSA检测诊断的晚期前列腺癌患者以及在临床局部疾病治疗方案（例如根治性前列腺切除术、放射治疗或观察）后PSA水平持续或升高的男性。
BACKGROUND
Prostate cancer is a leading cause of cancer death in men. Treatment goals for men with advanced prostate cancer include prolonging survival, preventing or delaying symptoms due to disease progression, improving and maintaining quality of life, reducing treatment related morbidity. Androgen suppression therapy is considered a mainstay of treatment for men with advanced prostate cancer. However it is not clear whether early androgen suppression for men with locally advanced disease or asymptomatic metastases improves length and quality of life compared to androgen suppression deferred until signs and symptoms of clinical progression.
OBJECTIVES
This systematic review assessed the efficacy and adverse effects of primary therapy with early versus deferred androgen suppression therapy in men with advanced prostate cancer.
SEARCH STRATEGY
Randomized controlled trials were searched in general and specialized databases (MEDLINE, EMBASE, CancerLIT, Cochrane Library, VA Cochrane Prostate Disease register) and by reviewing bibliographies including those of the Blue Cross and Blue Shield Association Technology Evaluation Center/Evidence-based Practice Center of the Agency for Healthcare Research and Quality (BCBS/TEC-AHRQ) report No.4.
SELECTION CRITERIA
All published randomized trials were eligible for inclusion provided they: randomized men with advanced prostate cancer to early versus deferred androgen suppression; reported overall, progression-free, and cancer-specific survival, and/or adverse events; did not utilize androgen suppression as adjuvant therapy to radiation treatment.
DATA COLLECTION AND ANALYSIS
An independent reviewer using a standardized form extracted information on trial characteristics, interventions, and outcomes. Results were reviewed for accuracy and discrepancies resolved by discussion. The main outcome measure for comparing effectiveness was the overall survival at 1, 2, 5 and 10 years. Progression-free survival, cancer-specific survival, complications due to disease progression and the incidence of adverse effects of treatment were also measured.
MAIN RESULTS
Four trials involving 2,167 patients were included in this review. All of the trials were conducted prior to use of prostate specific antigen (PSA) testing. There was variability between studies regarding the treatments used and the requirements for initiation of treatments. The percent overall survival at 1, 2, 5, and 10 years for the early treatment group was 88%, 73%, 44%, and 18%. For the deferred therapy group the percent overall survival was 86%, 71%, 37%, and 12%. The pooled estimate for the difference in overall survival favored early therapy but was significant only at 10 years when few patients had survived [OR = 1.16 (95% CI: 0.90 to 1.49) at 1 year, 1.08 (95% CI: 0.89 to 1.33) at 2 years, 1.19 (95% CI: 0.95 to 1.50) at 5 years, and 1.50 (95% CI: 1.04 to 2.16) at 10 years]. The pooled estimate of prostate cancer specific survival at 2, 5, and 10 years favored early therapy though the confidence intervals were wide and the results not statistically different. The risk differences at 2, 5, and 10 years were 2.7%, 5.8%, and 4.6%. Although each study used unique definitions of progression free survival, all studies found progression free survival was consistently better in the early intervention group at all time points. Complications due to disease progression were only reported in one study but were more frequent in the deferred treatment group. Adverse events due to treatment were also only reported in one study but occurred more frequently in the early treatment group.
REVIEWER'S CONCLUSIONS
The evidence from randomized controlled trials is limited by the variability in study design, stage of cancer and subjects enrolled, interventions utilized, definitions and reporting of outcomes and the lack of PSA testing for diagnostic and monitoring purposes. However, the available information suggests that early androgen suppression for treatment of advanced prostate cancer reduces disease progression and complications due to progression. Early androgen suppression may provide a small but statistically significant improvement in overall survival at 10 years. There was no statistically significant difference in prostate cancer specific survival but a clinically important difference could not be excluded. These outcomes need to be evaluated with the evidence suggesting higher costs and more frequent treatment related adverse effects with early therapy. Additional studies are required to evaluate more definitively the efficacy and adverse effects of early versus delayed androgen suppression in men with prostate cancer. In particular trials should evaluate patients with advanced prostate cancer diagnosed by PSA testing and men with persistent or rising PSA levels following treatment options (e.g. radical prostatectomy, radiation therapy or observation) for clinically localized disease.