East Kent Gynaecological Oncology Centre, Queen Elizabeth The Queen Mother Hospital, Margate, UK.
Institute of Health & Society, Newcastle University, Newcastle upon Tyne, UK.
Cochrane Database Syst Rev. 2022 Aug 22;8(8):CD010260. doi: 10.1002/14651858.CD010260.pub3.
BACKGROUND: This is an update of the Cochrane Review published in Issue 4, 2015. Cervical cancer is one of the most frequent cause of death from gynaecological cancers worldwide. Many new cervical cancer cases in low-income countries present at an advanced stage. Standard care in Europe and the US for locally advanced cervical cancer (LACC) is chemoradiotherapy. In low-income countries, with limited access to radiotherapy, LACC may be treated with chemotherapy and hysterectomy. It is not certain if this improves survival. It is important to assess the value of hysterectomy with radiotherapy or chemotherapy, or both, as an alternative. OBJECTIVES: To determine whether hysterectomy, in addition to standard treatment with radiotherapy or chemotherapy, or both, in women with LACC (Stage IB to III) is safe and effective compared with standard treatment alone. SEARCH METHODS: We searched CENTRAL, MEDLINE via Ovid, Embase via Ovid, LILACS, trial registries and the grey literature up to 3 February 2022. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) that compared treatments involving hysterectomy versus radiotherapy or chemotherapy, or both, in women with LACC International Federation of Gynecology and Obstetrics (FIGO) Stages IB to III. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We independently assessed study eligibility, extracted data and assessed the risk of bias. Where possible, we synthesised overall (OS) and progression-free (PFS) or disease-free (DFS) survival in a meta-analysis using a random-effects model. Adverse events (AEs) were incompletely reported and we described the results of single trials in narrative form. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: From the searches we identified 968 studies. After deduplication, title and abstract screening, and full-text assessment, we included 11 RCTs (2683 women) of varying methodological quality. This update identified four new RCTs and three ongoing RCTs. The included studies compared: hysterectomy (simple or radical) with radiotherapy or chemoradiotherapy or neoadjuvant chemotherapy (NACT) versus radiotherapy alone or chemoradiotherapy (CCRT) alone or CCRT and brachytherapy. There is also one ongoing study comparing three groups: hysterectomy with CCRT versus hysterectomy with NACT versus CCRT. There were two comparison groups for which we were able to do a meta-analysis. Hysterectomy (radical) with neoadjuvant chemotherapy versus chemoradiotherapy alone Two RCTs with similar design characteristics (620 and 633 participants) found no difference in five-year OS between NACT with hysterectomy versus CCRT. Meta-analysis assessing 1253 participants found no evidence of a difference in risk of death (OS) between women who received NACT plus hysterectomy and those who received CCRT alone (HR 0.94, 95% CI 0.76 to 1.16; moderate-certainty evidence). In both studies, the five-year DFS in the NACT plus surgery group was worse (57%) compared with the CCRT group (65.6%), mostly for Stage IIB. Results of single trials reported no apparent difference in long-term severe complications, grade 3 acute toxicity and severe late toxicity between groups (very low-quality evidence). Hysterectomy (simple or radical) with neoadjuvant chemotherapy versus radiotherapy alone Meta-analysis of three trials of NACT with hysterectomy versus radiotherapy alone, assessing 571 participants, found that women who received NACT plus hysterectomy had less risk of death (OS) than those who received radiotherapy alone (HR 0.71, 95% CI 0.55 to 0.93; I = 0%; moderate-quality evidence). However, a significant number of participants who received NACT plus hysterectomy also had radiotherapy. There was no difference in the proportion of women with disease progression or recurrence (DFS and PFS) between NACT plus hysterectomy and radiotherapy groups (RR 0.75, 95% CI 0.53 to 1.05; I = 20%; moderate-quality evidence). The certainty of the evidence was low or very-low for all other comparisons for all outcomes. None of the trials reported quality of life outcomes. AUTHORS' CONCLUSIONS: From the available RCTs, we found insufficient evidence that hysterectomy with radiotherapy, with or without chemotherapy, improves the survival of women with LACC who are treated with radiotherapy or CCRT alone. The overall certainty of the evidence was variable across the different outcomes and was universally downgraded due to concerns about risk of bias. The certainty of the evidence for NACT and radical hysterectomy versus radiotherapy alone for survival outcomes was moderate. The same occurred for the comparison involving NACT and hysterectomy compared with CCRT alone. Evidence from other comparisons was generally sparse and of low or very low-certainty. This was mainly based on poor reporting and sparseness of data where results were based on single trials. More trials assessing medical management with and without hysterectomy may test the robustness of the findings of this review as further research is likely to have an important impact on our confidence in the estimate of effect.
背景:这是 2015 年第 4 期 Cochrane 综述的更新。宫颈癌是全球妇科癌症死亡的最常见原因之一。许多低收入国家的新宫颈癌病例处于晚期。欧洲和美国对局部晚期宫颈癌(LACC)的标准治疗是放化疗。在资源有限的低收入国家,LACC 可能采用化疗和子宫切除术进行治疗。目前尚不确定这是否能提高生存率。评估在标准治疗(放疗或化疗或两者联合)基础上加用子宫切除术的价值很重要,因为它是一种替代治疗方法。 目的:确定与单独接受放疗或化疗或两者联合的标准治疗相比,在 LACC(FIGO 分期 IB 至 III 期)患者中,子宫切除术加放疗或化疗或两者联合是否安全有效。 检索方法:我们检索了 CENTRAL、MEDLINE(通过 Ovid)、Embase(通过 Ovid)、LILACS、试验注册库和灰色文献,检索截至 2022 年 2 月 3 日。 选择标准:我们检索了比较子宫切除术与放疗或化疗或两者联合与单独接受放疗或化疗或两者联合治疗 LACC 的随机对照试验(RCT)。国际妇产科联合会(FIGO)分期 IB 至 III 期。 数据收集和分析:我们使用了 Cochrane 预期的标准方法学程序。我们独立评估了研究的纳入标准、提取数据并评估了偏倚风险。在可能的情况下,我们使用随机效应模型对总体生存(OS)和无进展生存(PFS)或疾病无复发生存(DFS)进行了荟萃分析。不良事件(AE)报告不完整,我们以叙述形式描述了单个试验的结果。我们使用 GRADE 方法评估证据的确定性。 主要结果:从检索中我们确定了 968 项研究。经过去重、标题和摘要筛选以及全文评估,我们纳入了 11 项 RCT(2683 名女性),这些 RCT 的方法学质量各不相同。本次更新发现了四项新 RCT 和三项正在进行的 RCT。纳入的研究比较了:子宫切除术(单纯性或根治性)与放疗或放化疗或新辅助化疗(NACT)与单纯放疗或放化疗联合治疗或放化疗联合近距离治疗。还有一项正在进行的研究比较了三组:子宫切除术联合放化疗与子宫切除术联合 NACT 与放化疗联合治疗。有两组我们可以进行荟萃分析。 NACT 联合根治性子宫切除术与单纯放化疗比较:两项设计特征相似的 RCT(620 名和 633 名参与者)发现,NACT 联合子宫切除术与单纯放化疗相比,五年 OS 无差异。纳入 1253 名参与者的荟萃分析发现,接受 NACT 加子宫切除术的女性与接受单纯放化疗的女性在死亡风险(OS)方面没有差异(HR 0.94,95%CI 0.76 至 1.16;中等确定性证据)。在这两项研究中,NACT 加手术组的五年 DFS 较差(57%),而单纯放化疗组为 65.6%(主要为 IIB 期)。单试验报告结果表明,两组之间严重并发症、3 级急性毒性和严重晚期毒性的长期严重程度无明显差异(极低质量证据)。 NACT 联合根治性子宫切除术与单纯放疗比较:对 3 项 NACT 联合子宫切除术与单纯放疗的试验进行荟萃分析,评估了 571 名参与者,发现接受 NACT 加子宫切除术的女性死亡风险(OS)低于单纯放疗组(HR 0.71,95%CI 0.55 至 0.93;I = 0%;中等质量证据)。然而,许多接受 NACT 加子宫切除术的参与者也接受了放疗。NACT 加子宫切除术组和单纯放疗组的疾病进展或复发(DFS 和 PFS)比例无差异(RR 0.75,95%CI 0.53 至 1.05;I = 20%;中等质量证据)。对于所有其他结局,所有其他比较的证据确定性都很低或非常低。没有一项试验报告生活质量结局。 作者结论:根据现有 RCT,我们没有充分证据表明在接受放疗或放化疗联合治疗的 LACC 患者中,子宫切除术联合放疗,无论是否联合化疗,都能提高生存率。不同结局的证据确定性存在差异,普遍因偏倚风险而降低。NACT 和根治性子宫切除术与单纯放疗比较生存结局的证据确定性为中等。NACT 与子宫切除术比较单纯放化疗的结果也如此。其他比较的证据普遍较少,且质量较低或非常低。这主要是基于不良报告和数据稀疏,结果基于单个试验。进一步评估包含医学治疗和不包含子宫切除术的随机对照试验可能会检验本综述结果的稳健性,因为进一步的研究可能会对我们对效应估计的信心产生重要影响。
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