Frost Jonathan A, Webster Katie E, Bryant Andrew, Morrison Jo
Obstetrics and Gynaecology, Gloucestershire Hospitals NHS Foundation Trust, Great Western Road, Gloucester, UK, GL1 3NN.
Cochrane Database Syst Rev. 2017 Oct 2;10(10):CD007585. doi: 10.1002/14651858.CD007585.pub4.
BACKGROUND: This is an update of a previous Cochrane review published in Issue 1, 2010 and updated in Issue 9, 2015. The role of lymphadenectomy in surgical management of endometrial cancer remains controversial. Lymph node metastases can be found in approximately 10% of women who before surgery are thought to have cancer confined to the womb. Removal of all pelvic and para-aortic lymph nodes (lymphadenectomy) at initial surgery has been widely advocated, and pelvic and para-aortic lymphadenectomy remains part of the FIGO (International Federation of Gynaecology and Obstetrics) staging system for endometrial cancer. This recommendation is based on data from studies that suggested improvement in survival following pelvic and para-aortic lymphadenectomy. However, these studies were not randomised controlled trials (RCTs), and treatment of pelvic lymph nodes may not confer a direct therapeutic benefit, other than allocating women to poorer prognosis groups. Furthermore, the Cochrane review and meta-analysis of RCTs of routine adjuvant radiotherapy to treat possible lymph node metastases in women with early-stage endometrial cancer found no survival advantage. Surgical removal of pelvic and para-aortic lymph nodes has serious potential short-term and long-term sequelae. Therefore, it is important to investigate the clinical value of this treatment. OBJECTIVES: To evaluate the effectiveness and safety of lymphadenectomy for the management of endometrial cancer. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase to June 2009 for the original review, updated the search to June 2015 for the last updated version and further extended the search to March 2017 for this version of the review. We also searched registers of clinical trials, abstracts of scientific meetings, and reference lists of included studies, and we contacted experts in the field. SELECTION CRITERIA: RCTs and quasi-RCTs that compared lymphadenectomy versus no lymphadenectomy in adult women diagnosed with endometrial cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias. Hazard ratios (HRs) for overall and progression-free survival and risk ratios (RRs) comparing adverse events in women who received lymphadenectomy versus those with no lymphadenectomy were pooled in random-effects meta-analyses. We assessed the quality of the evidence using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. MAIN RESULTS: 978 unique references were identified via the search strategy. All but 50 were excluded by title and abstract screening. Three RCTs met the inclusion criteria; for one small RCT, data were insufficient for inclusion in the meta-analysis. The two RCTs included in the analysis randomly assigned 1945 women, reported HRs for survival adjusted for prognostic factors and based on 1851 women and had an overall low risk of bias, as they satisfied four of the assessment criteria. The third study had an overall unclear risk of bias, as information provided was not adequate concerning random sequence generation, allocation concealment, blinding, or completeness of outcome reporting.Results of the meta-analysis remained unchanged from the previous versions of this review and indicated no differences in overall and recurrence-free survival between women who underwent lymphadenectomy and those who did not undergo lymphadenectomy (pooled hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.81 to 1.43; HR 1.23, 95% CI 0.96 to 1.58 for overall and recurrence-free survival, respectively) (1851 participants, two studies; moderate-quality evidence).We found no difference in risk of direct surgical morbidity between women who underwent lymphadenectomy and those who did not undergo lymphadenectomy. However, women who underwent lymphadenectomy had a significantly higher risk of surgery-related systemic morbidity and lymphoedema/lymphocyst formation than those who did not undergo lymphadenectomy (RR 3.72, 95% CI 1.04 to 13.27; RR 8.39, 95% CI 4.06 to 17.33 for risk of surgery-related systemic morbidity and lymphoedema/lymphocyst formation, respectively) (1922 participants, two studies; high-quality evidence). AUTHORS' CONCLUSIONS: This review found no evidence that lymphadenectomy decreases risk of death or disease recurrence compared with no lymphadenectomy in women with presumed stage I disease. Evidence on serious adverse events suggests that women who undergo lymphadenectomy are more likely to experience surgery-related systemic morbidity or lymphoedema/lymphocyst formation. Currently, no RCT evidence shows the impact of lymphadenectomy in women with higher-stage disease and in those at high risk of disease recurrence.
背景:这是对之前发表于2010年第1期并于2015年第9期更新的Cochrane系统评价的更新。淋巴结切除术在子宫内膜癌手术治疗中的作用仍存在争议。在术前被认为癌症局限于子宫的女性中,约10%可发现淋巴结转移。在初次手术时切除所有盆腔及腹主动脉旁淋巴结(淋巴结切除术)已得到广泛提倡,盆腔及腹主动脉旁淋巴结切除术仍是国际妇产科联盟(FIGO)子宫内膜癌分期系统的一部分。该推荐基于一些研究数据,这些数据提示盆腔及腹主动脉旁淋巴结切除术后生存率有所提高。然而,这些研究并非随机对照试验(RCT),而且盆腔淋巴结的处理可能除了将女性分配到预后较差的组外,并不会带来直接的治疗益处。此外,Cochrane对早期子宫内膜癌女性常规辅助放疗以治疗可能的淋巴结转移的RCT进行的系统评价和荟萃分析未发现生存优势。手术切除盆腔及腹主动脉旁淋巴结有严重的潜在短期和长期后遗症。因此,研究这种治疗的临床价值很重要。 目的:评估淋巴结切除术治疗子宫内膜癌的有效性和安全性。 检索方法:我们检索了Cochrane对照试验中心注册库(CENTRAL)、MEDLINE和Embase至2009年6月以获取原始评价,将检索更新至2015年6月以获取上次更新版本,并进一步将检索扩展至2017年3月以获取本版评价。我们还检索了临床试验注册库、科学会议摘要以及纳入研究的参考文献列表,并联系了该领域的专家。 选择标准:比较淋巴结切除术与未行淋巴结切除术在诊断为子宫内膜癌的成年女性中的RCT和半RCT。 数据收集与分析:两位评价作者独立提取数据并评估偏倚风险。将接受淋巴结切除术与未接受淋巴结切除术的女性的总生存和无进展生存的风险比(HR)以及不良事件的风险比(RR)进行汇总,采用随机效应荟萃分析。我们使用GRADE(推荐分级、评估、制定与评价)方法评估证据质量。 主要结果:通过检索策略共识别出978篇独特的参考文献。除50篇外,其余均通过标题和摘要筛选被排除。三项RCT符合纳入标准;一项小型RCT数据不足,未纳入荟萃分析。纳入分析的两项RCT随机分配了1945名女性,报告了根据预后因素调整的生存HR,基于1851名女性,且总体偏倚风险较低,因为它们满足四项评估标准。第三项研究总体偏倚风险不明确,因为提供的关于随机序列生成、分配隐藏、盲法或结局报告完整性的信息不足。荟萃分析结果与本评价的先前版本一致,表明接受淋巴结切除术与未接受淋巴结切除术的女性在总生存和无复发生存方面无差异(汇总HR 1.07,95%置信区间(CI)0.81至1.43;总生存和无复发生存的HR分别为1.23,95%CI 0.96至1.58)(1851名参与者,两项研究;中等质量证据)。我们发现接受淋巴结切除术与未接受淋巴结切除术的女性在直接手术并发症风险方面无差异。然而,接受淋巴结切除术的女性发生手术相关全身并发症和淋巴水肿/淋巴囊肿形成的风险显著高于未接受淋巴结切除术的女性(RR 3.72,95%CI 1.04至13.27;手术相关全身并发症和淋巴水肿/淋巴囊肿形成风险的RR分别为8.39,95%CI 4.06至17.33)(1922名参与者,两项研究;高质量证据)。 作者结论:本评价未发现证据表明与未行淋巴结切除术相比,淋巴结切除术能降低假定为I期疾病女性的死亡风险或疾病复发风险。关于严重不良事件的证据表明,接受淋巴结切除术的女性更有可能经历手术相关全身并发症或淋巴水肿/淋巴囊肿形成。目前,尚无RCT证据显示淋巴结切除术对更高分期疾病女性和疾病复发高风险女性的影响。
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