Surgical cytoreduction for recurrent epithelial ovarian cancer

  • Review
  • Intervention

Authors


Abstract

Background

The standard management of primary ovarian cancer is optimal cytoreductive surgery followed by platinum-based chemotherapy. Most women with primary ovarian cancer achieve remission on this combination therapy. For women achieving clinical remission after completion of initial treatment, most (60%) with advanced epithelial ovarian cancer will ultimately develop recurrent disease. However, the standard treatment of women with recurrent ovarian cancer remains poorly defined. Surgery for recurrent ovarian cancer has been suggested to be associated with increased overall survival.

Objectives

To evaluate the effectiveness and safety of optimal secondary cytoreductive surgery for women with recurrent epithelial ovarian cancer. To assess the impact of various residual tumour sizes, over a range between 0 cm and 2 cm, on overall survival.

Search methods

We searched the Cochrane Gynaecological Cancer Group Trials Register, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) up to December 2012. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. For databases other than MEDLINE, the search strategy has been adapted accordingly.

Selection criteria

Retrospective data on residual disease, or data from randomised controlled trials (RCTs) or prospective/retrospective observational studies that included a multivariate analysis of 50 or more adult women with recurrent epithelial ovarian cancer, who underwent secondary cytoreductive surgery with adjuvant chemotherapy. We only included studies that defined optimal cytoreduction as surgery leading to residual tumours with a maximum diameter of any threshold up to 2 cm.

Data collection and analysis

Two review authors (KG, TA) independently abstracted data and assessed risk of bias. Where possible the data were synthesised in a meta-analysis.

Main results

There were no RCTs; however, we found nine non-randomised studies that reported on 1194 women with comparison of residual disease after secondary cytoreduction using a multivariate analysis that met our inclusion criteria. These retrospective and prospective studies assessed survival after secondary cytoreductive surgery in women with recurrent epithelial ovarian cancer.

Meta- and single-study analyses show the prognostic importance of complete cytoreduction to microscopic disease, since overall survival was significantly prolonged in these groups of women (most studies showed a large statistically significant greater risk of death in all residual disease groups compared to microscopic disease).

Recurrence-free survival was not reported in any of the studies. All of the studies included at least 50 women and used statistical adjustment for important prognostic factors. One study compared sub-optimal (> 1 cm) versus optimal (< 1 cm) cytoreduction and demonstrated benefit to achieving cytoreduction to less than 1 cm, if microscopic disease could not be achieved (hazard ratio (HR) 3.51, 95% CI 1.84 to 6.70). Similarly, one study found that women whose tumour had been cytoreduced to less than 0.5 cm had less risk of death compared to those with residual disease greater than 0.5 cm after surgery (HR not reported; P value < 0.001).

There is high risk of bias due to the non-randomised nature of these studies, where, despite statistical adjustment for important prognostic factors, selection is based on retrospective achievability of cytoreduction, not an intention to treat, and so a degree of bias is inevitable.

Adverse events, quality of life and cost-effectiveness were not reported in any of the studies.

Authors' conclusions

In women with platinum-sensitive recurrent ovarian cancer, ability to achieve surgery with complete cytoreduction (no visible residual disease) is associated with significant improvement in overall survival. However, in the absence of RCT evidence, it is not clear whether this is solely due to surgical effect or due to tumour biology. Indirect evidence would support surgery to achieve complete cytoreduction in selected women. The risks of major surgery need to be carefully balanced against potential benefits on a case-by-case basis.

摘要

外科肿瘤细胞减灭术治疗复发性上皮性卵巢癌

研究背景

原发性卵巢癌的治疗标准是在满意的肿瘤减灭术之后使用铂类药物化疗。 这种组合疗法可以使得大多数女性患者达到缓解。 达到临床缓解后,多数患者(60%)治疗晚期会肿瘤复发。 然而,女性患有复发性卵巢癌的治疗标准还很模糊。 外科手术被认为与延长整体生存率有关。

研究目的

评估满意的再次肿瘤细胞减灭术在复发性上皮性卵巢癌有效性和安全性, 并且评估术后范围在2 厘米以内的残余肿瘤大小对总体生存率的影响。

检索策略

我们检索了截至2012 年 12 月的Cochrane 妇科肿瘤临床试验数据库(Cochrane Gynaecological Cancer Group Trials Register)、MEDLINE、EMBASE 和Cochrane 中央对照试验登记册(CENTRAL)。 我们还检索了临床试验研究、会议摘要、纳入研究的参考文献和联系了该领域的专家。 除 MDELINE 数据库外,搜索策略根据相应情况而定。

标准/纳入排除标准

回顾性残留肿瘤数据或随机对照试验(RCT) 数据或前瞻/回顾观察研究包括50名或以上成年女性复发性卵巢上皮癌并接受辅助化疗及再次肿瘤细胞减灭术案例的多元分析。 我们只纳入那些理想肿瘤减灭术的残余肿瘤最大直径为任何阈值达 2 厘米的研究。

数据收集与分析

两名审阅作者 (KG,TA) 独立提取数据和评估误差风险。 在可能情况下整合数据进行荟萃分析(meta分析)。

主要结果

尽管没有随机对照试验,我们纳入9个非随机研究其中包括使用多元分析比较残留肿瘤在再次肿瘤细胞灭活术后1194名女患者。 这些回顾性和前瞻性的研究评估女性复发性上皮性卵巢癌再次肿瘤细胞减灭术后的生存期。

荟萃和单个研究分析显示彻底的肿瘤减灭术和微小肿瘤残余对预后的重要性,因为总体生存率在这些人群中显著延长 (大多数的研究表明所有残留病组要比微小肿瘤残余组在统计学上有着更大死亡风险率)。

无复发的生存率现有研究中未报道。 所有的研究包括至少 50 名女性患者并对重要的预后参数进行了统计调整。 一项研究比较次理想 (> 1 厘米) 与理想 (< 1 厘米) 肿瘤减灭术,结果显示如果微小肿瘤残余不能达到,小于 1 厘米肿瘤残余预后更好(危害比 (HR) 3.51,95%置信区间 1.84 到 6.70)。 同样,一项研究发现,女性体内的肿瘤残余小于 0.5 厘米要比那些有残留病灶大于 0.5 厘米 (HR没报道; p 值 < 0.001) 手术后死亡的风险较小。

由于这些研究非随机性导致误差风险比较高,尽管重要预后因素参数进行了统计调整,但是选择基于回顾性研究肿瘤减灭术,因此一定程度的误差是不可避免的。

不良事件、 生活质量和成本效益没有在任何研究中报道。

作者结论

在铂类化疗药物敏感的复发性卵巢癌的女性患者中,与实现彻底性肿瘤灭活术(无可见肿瘤残留) 的与总体生存率显著改善有关。 然而,由于缺乏随机临床试验证据,尚不清楚这是否完全是因为手术效果或由于肿瘤生物学特性。 在某些女性患者中,间接证据支持彻底性肿瘤灭活手术。 重大手术的风险需要按个案谨慎权评估潜在的好处。

翻译注解

译者:崔龙 黄志超(香港中文大学妇产科);审校:李迅。翻译由北京中医药大学循证医学中心组织和提供。

Plain language summary

Surgery to remove tumour so that it is not visible with the naked eye prolongs survival in women with recurrent epithelial ovarian cancer

Epithelial ovarian cancer is a disease in which malignant cells form in the tissue covering the ovary. It accounts for about 90% of ovarian cancers; the remaining 10% arise from germ cells or the sex cords and stroma of the ovary. Women with epithelial ovarian cancer that has returned after primary treatment (recurrent disease) may need secondary surgery to remove all or part of the cancer. When ovarian cancer recurs after more than six months it is considered suitable for further treatment with platinum chemotherapy (platinum sensitive).

The results of this review suggest that surgery may be associated with improved outcomes in terms of prolonging life in some women (platinum-sensitive disease). In particular, surgery removing all visible disease is associated with a significant improvement in survival, although this may be due to the cancer biology facilitating surgery, rather than the surgery itself. We conclude from the current evidence that surgery with the aim of removing all visible disease should be considered in women with recurrent ovarian cancer on an individual basis. However, the data are limited to non-randomised studies with a median age of women in their 50s and early 60s, which may not be representative of all women with ovarian cancer. The risks of major surgery need to be carefully balanced against potential benefits on a case-by-case basis.

概要

手术切除肉眼可见的肿瘤后,复发性上皮性卵巢癌患者生存期可以得到延长。

上皮性卵巢癌来源于覆盖在卵巢表面的恶性生发上皮。 它占了恶性肿瘤的大部分(约90%),剩余的约10%来自生殖细胞或性索-间质细胞。 经过初期治疗后复发 (肿瘤复发) 的上皮性卵巢癌患者可能需要二次手术来切除全部或部分的超过六个月复发的卵巢癌被认为是适合于铂类药物化疗(铂类药物敏感) 处理。

本综述研究结果表明手术可能会改善一些患者的预后如延长铂类药物敏感女性生存期。 尤其是,手术切除所有肉眼可见的肿瘤组织有利于延长患者生存期,虽然这可能是由于肿瘤生物学特性有利于手术治疗,而不是手术本身原因。 从目前的证据来看,我们认为应该从个体患者基础上来考虑手术切除复发性卵巢癌女性的可能性。 然而,数据仅限于非随机研究中位数年龄在50和60岁之间,这不代表所有患有卵巢癌的女性。 重大手术的风险需在个案的基础上来谨慎评估潜在的利弊。

翻译注解

译者:崔龙 黄志超(香港中文大学妇产科);审校:李迅。翻译由北京中医药大学循证医学中心组织和提供。

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