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.
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.
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.
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.
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.
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.
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。
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。
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。
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。
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）。
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。
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。