Moffatt Joanne, Webster Katie E, Dwan Kerry, Frost Jonathan A, Morrison Jo
Department of Gynaecological Oncology, GRACE Centre, Musgrove Park Hospital, Somerset NHS Foundation Trust, Taunton, UK.
Population Health Sciences, University of Bristol, Bristol, UK.
Cochrane Database Syst Rev. 2025 Jun 10;6(6):CD015786. doi: 10.1002/14651858.CD015786.pub2.
RATIONALE: Endometrial cancer, which affects the lining of the uterus, is the most common form of uterine cancer (96%), and the sixth most common cancer in females worldwide, accounting for 4.5% of all cancers in females. In 2022, there were 420,242 cases of uterine cancer and 97,704 deaths from the disease worldwide. Most women have early-stage endometrial cancer at diagnosis. Traditionally, surgical staging included removal of all lymph nodes (lymphadenectomy) in the pelvis (pelvic lymphadenectomy) with or without para-aortic areas (pelvic/para-aortic lymphadenectomy), to determine the need for further treatment. However, rates of lymph node involvement are relatively low and may be predicted by uterine histopathology and molecular markers. Lymphadenectomy carries a significant risk of long-term morbidity from lymphoedema and previous studies comparing pelvic lymphadenectomy with no lymphadenectomy found no survival benefit. Detecting the first draining lymph node(s) from each side of the uterus, called sentinel lymph node biopsy, can replace lymphadenectomy in terms of accuracy of detecting nodes, but no studies have shown whether sentinel lymph node biopsy is beneficial to women, despite its wide use. OBJECTIVES: To evaluate the benefits and harms of lymphadenectomy and sentinel lymph node biopsy for the management of endometrial cancer comparing different head-to-head comparisons in a network meta-analysis allowing ranking of treatment strategies. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov and the WHO ICTRP for studies up to 22 March 2024. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) of women with early-stage endometrial cancer, comparing combinations of no lymphadenectomy, pelvic lymphadenectomy, pelvic/para-aortic lymphadenectomy and sentinel lymph node biopsy. We excluded non-randomised studies and studies assessing diagnostic test accuracy of lymph node sampling. OUTCOMES: Overall survival; progression-free survival; morbidity and mortality related to surgery; early and late adverse events, including lymphoedema and lymphocyst formation; and quality of life. RISK OF BIAS: We used RoB 2 to assess risk of bias. SYNTHESIS METHODS: We conducted meta-analyses using random-effects models to calculate hazard ratios (HR) for time-to-event data and risk ratios (RR) and mean difference (MD) for other outcomes, with 95% confidence intervals (CI). We used GRADE to summarise the certainty of evidence. We intended to compare treatments in a network meta-analysis. INCLUDED STUDIES: We included five RCTs (one remains ongoing) with 2074 women. Studies were conducted in the UK, South Africa, Poland, New Zealand, Chile, Italy, Egypt and Brazil, and published between 2008 and 2023. Another 10 studies are ongoing. Three studies (1955 participants) compared no lymphadenectomy with pelvic lymphadenectomy, one study (50 participants) compared no lymphadenectomy with pelvic/para-aortic lymphadenectomy, and one study (69 participants - ongoing) compared sentinel lymph node biopsy with pelvic/para-aortic lymphadenectomy. SYNTHESIS OF RESULTS: No lymphadenectomy versus pelvic lymphadenectomy No lymphadenectomy probably results in little to no difference in overall survival (HR 0.85, 95% CI 0.66 to 1.10; 2 studies, 1922 participants; moderate-certainty evidence) and improves progression-free survival (HR 0.78, 95% CI 0.63 to 0.96; 2 studies, 1922 participants; high-certainty evidence) compared to pelvic lymphadenectomy. No lymphadenectomy may reduce early adverse effects from direct surgical morbidity slightly (RR 0.68, 95% CI 0.27 to 1.71; 3 studies, 1955 participants; low-certainty evidence) and probably reduces early adverse effects due to surgically related systemic morbidity (RR 0.28, 95% CI 0.09 to 0.93; 3 studies, 1955 participants; moderate-certainty evidence). No lymphadenectomy probably results in a large reduction in lymphoedema (RR 0.12, 95% CI 0.05 to 0.26; 3 studies, 1955 participants; moderate-certainty evidence) and likely reduces lymphocyst formation (RR 0.20, 95% CI 0.04 to 0.91; 1 study, 1403 participants; moderate-certainty evidence). There were no quality of life data. Sentinel lymph node biopsy versus pelvic/para-aortic lymphadenectomy One study shared unpublished data and the evidence is very uncertain about the effect of sentinel lymph node biopsy on overall survival, progression-free survival, early adverse events, lymphocyst formation and quality of life at 12 months. Sentinel lymph node biopsy compared with pelvic/para-aortic lymphadenectomy probably reduces the development of lymphoedema (RR 0.30, 95% CI 0.09 to 0.97; 1 study, 69 participants; moderate-certainty evidence). No lymphadenectomy versus pelvic/para-aortic lymphadenectomy One study closed after the recruitment of 50 participants due to slow uptake, and we were unable to extract data for use in the meta-analysis. Because of this, we were unable to form a linked network for meta-analysis. Other comparisons Studies of other comparisons are ongoing or results are yet to be published. AUTHORS' CONCLUSIONS: Data suggest 'less is probably more' in terms of surgical staging for women with presumed endometrial cancer, as no lymphadenectomy is favoured over pelvic lymphadenectomy in terms of important outcomes, with overall moderate certainty. Preliminary results for sentinel lymph node biopsy versus pelvic/para-aortic lymphadenectomy have a similar direction of effect, but the evidence is very uncertain. Data from several studies are ongoing. However, given the weight of evidence that supports no lymphadenectomy over lymphadenectomy, our ability to make adjuvant treatment decisions based on uterine factors, and the advent of molecular profiling, it is disappointing that only one study compared no lymphadenectomy with sentinel lymph node biopsy, potentially putting many women at continued risk of short- and significant long-term consequences of extensive lymphadenectomy. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: This review is based on an updated protocol including network meta-analysis methods and new RoB 2 assessment of a previously published review. Updated protocol 2023 available via https://doi.org/10.1002/14651858.CD015786.
理论依据：子宫内膜癌影响子宫内膜，是子宫癌最常见的形式（占96%），也是全球女性中第六大常见癌症，占女性所有癌症的4.5%。2022年，全球有420,242例子宫癌病例，97,704人死于该疾病。大多数女性在确诊时患有早期子宫内膜癌。传统上，手术分期包括切除盆腔内所有淋巴结（盆腔淋巴结清扫术），可选择或不选择切除腹主动脉旁区域（盆腔/腹主动脉旁淋巴结清扫术），以确定是否需要进一步治疗。然而，淋巴结受累率相对较低，可通过子宫组织病理学和分子标志物进行预测。淋巴结清扫术存在淋巴水肿导致长期发病的重大风险，以往比较盆腔淋巴结清扫术与不进行淋巴结清扫术的研究未发现生存获益。检测子宫两侧的首个引流淋巴结，即前哨淋巴结活检，在检测淋巴结的准确性方面可替代淋巴结清扫术，但尽管其应用广泛，尚无研究表明前哨淋巴结活检对女性有益。 目的：通过网络荟萃分析中不同的直接比较，评估淋巴结清扫术和前哨淋巴结活检在子宫内膜癌治疗中的益处和危害，从而对治疗策略进行排名。 检索方法：我们检索了CENTRAL、MEDLINE、Embase、ClinicalTrials.gov和世界卫生组织国际临床试验注册平台，检索截至2024年3月22日的研究。 纳入标准：我们纳入了早期子宫内膜癌女性的随机对照试验（RCT），比较不进行淋巴结清扫术、盆腔淋巴结清扫术、盆腔/腹主动脉旁淋巴结清扫术和前哨淋巴结活检的组合。我们排除了非随机研究和评估淋巴结取样诊断试验准确性的研究。 结局指标：总生存期；无进展生存期；与手术相关的发病率和死亡率；早期和晚期不良事件，包括淋巴水肿和淋巴囊肿形成；以及生活质量。 偏倚风险：我们使用RoB 2评估偏倚风险。 综合方法：我们使用随机效应模型进行荟萃分析，计算事件发生时间数据的风险比（HR）以及其他结局指标的风险比（RR）和平均差（MD），并给出%置信区间（CI）。我们使用GRADE总结证据的确定性。我们打算在网络荟萃分析中比较各种治疗方法。 纳入研究：我们纳入了5项RCT（1项仍在进行中），涉及2074名女性。研究在英国、南非、波兰、新西兰、智利、意大利埃及和巴西进行，发表于2008年至2023年之间。另有10项研究正在进行中。3项研究（1955名参与者）比较了不进行淋巴结清扫术与盆腔淋巴结清扫术，1项研究（50名参与者）比较了不进行淋巴结清扫术与盆腔/腹主动脉旁淋巴结清扫术，1项研究（69名参与者，正在进行中）比较了前哨淋巴结活检与盆腔/腹主动脉旁淋巴结清扫术。 结果综合：不进行淋巴结清扫术与盆腔淋巴结清扫术相比 与盆腔淋巴结清扫术相比，不进行淋巴结清扫术可能在总生存期方面几乎没有差异（HR 0.85，95% CI 0.66至1.10；2项研究，1922名参与者；中等确定性证据），并可改善无进展生存期（HR 0.78，95% CI 0.63至0.96；2项研究，1922名参与者；高确定性证据）。不进行淋巴结清扫术可能会略微降低直接手术发病率导致的早期不良反应（RR 0.68，95% CI 0.27至1.71；3项研究，1955名参与者；低确定性证据），并可能降低手术相关全身发病率导致的早期不良反应（RR 0.28，95% CI 0.09至0.93；3项研究，1955名参与者；中等确定性证据）。不进行淋巴结清扫术可能会大幅降低淋巴水肿的发生率（RR 0.12，95% CI 0.05至0.26；3项研究，1955名参与者；中等确定性证据），并可能降低淋巴囊肿的形成（RR 0.20，95% CI 0.04至0.91；1项研究，1403名参与者；中等确定性证据）。没有生活质量数据。前哨淋巴结活检与盆腔/腹主动脉旁淋巴结清扫术相比 一项研究分享了未发表的数据，关于前哨淋巴结活检对总生存期、无进展生存期、早期不良事件、淋巴囊肿形成和12个月时生活质量的影响，证据非常不确定。与盆腔/腹主动脉旁淋巴结清扫术相比，前哨淋巴结活检可能会降低淋巴水肿的发生率（RR 0.30，95% CI 0.09至0.97；1项研究，69名参与者；中等确定性证据）。不进行淋巴结清扫术与盆腔/腹主动脉旁淋巴结清扫术相比 一项研究在招募了50名参与者后因入组缓慢而结束，我们无法提取数据用于荟萃分析。因此，我们无法形成用于荟萃分析的关联网络。其他比较 其他比较的研究正在进行中或结果尚未发表。 作者结论：数据表明，对于疑似子宫内膜癌的女性，手术分期方面“少可能更好”，因为在重要结局方面，不进行淋巴结清扫术优于盆腔淋巴结清扫术，总体确定性中等。前哨淋巴结活检与盆腔/腹主动脉旁淋巴结清扫术比较的初步结果具有相似的效应方向，但证据非常不确定。多项研究的数据正在进行中。然而，鉴于支持不进行淋巴结清扫术优于淋巴结清扫术的证据权重、我们基于子宫因素做出辅助治疗决策的能力以及分子谱分析的出现，令人失望的是，只有一项研究比较了不进行淋巴结清扫术与前哨淋巴结活检，这可能使许多女性继续面临广泛淋巴结清扫术带来的短期和重大长期后果的风险。 资金来源：本Cochrane综述没有专项资金。 注册情况：本综述基于一份更新的方案，包括网络荟萃分析方法以及对先前发表综述的新RoB 2评估。更新方案2023可通过https://doi.org/10.1002/14651858.CD015786获取。
Zotero 插件