Elattar Ahmed, Bryant Andrew, Winter-Roach Brett A, Hatem Mohamed, Naik Raj
Birmingham City Hospital, Dudley Road, Birmingham, West Midlands, UK, B18 7QH.
Cochrane Database Syst Rev. 2011 Aug 10;2011(8):CD007565. doi: 10.1002/14651858.CD007565.pub2.
Ovarian cancer is the sixth most common cancer among women. In addition to diagnosis and staging, primary surgery is performed to achieve optimal cytoreduction (surgical efforts aimed at removing the bulk of the tumour) as the amount of residual tumour is one of the most important prognostic factors for survival of women with epithelial ovarian cancer. An optimal outcome of cytoreductive surgery remains a subject of controversy to many practising gynae-oncologists. The Gynaecologic Oncology group (GOG) currently defines 'optimal' as having residual tumour nodules each measuring 1 cm or less in maximum diameter, with complete cytoreduction (microscopic disease) being the ideal surgical outcome. Although the size of residual tumour masses after surgery has been shown to be an important prognostic factor for advanced ovarian cancer, it is unclear whether it is the surgical procedure that is directly responsible for the superior outcome that is associated with less residual disease.
To evaluate the effectiveness and safety of optimal primary cytoreductive surgery for women with surgically staged advanced epithelial ovarian cancer (stages III and IV).To assess the impact of various residual tumour sizes, over a range between zero and 2 cm, on overall survival.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3) and the Cochrane Gynaecological Cancer Review Group Trials Register, MEDLINE and EMBASE (up to August 2010). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field.
Retrospective data on residual disease from randomised controlled trials (RCTs) or prospective and retrospective observational studies which included a multivariate analysis of 100 or more adult women with surgically staged advanced epithelial ovarian cancer and who underwent primary cytoreductive surgery followed by adjuvant platinum-based 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.
Two review authors independently abstracted data and assessed risk of bias. Where possible, the data were synthesised in a meta-analysis.
There were no RCTs or prospective non-RCTs identified that were designed to evaluate the effectiveness of surgery when performed as a primary procedure in advanced stage ovarian cancer.We found 11 retrospective studies that included a multivariate analysis that met our inclusion criteria. Analyses showed the prognostic importance of complete cytoreduction, where the residual disease was microscopic that is no visible disease, as overall (OS) and progression-free survival (PFS) were significantly prolonged in these groups of women. PFS was not reported in all of the studies but was sufficiently documented to allow firm conclusions to be drawn.When we compared suboptimal (> 1 cm) versus optimal (< 1 cm) cytoreduction the survival estimates were attenuated but remained statistically significant in favour of the lower volume disease group There was no significant difference in OS and only a borderline difference in PFS when residual disease of > 2 cm and < 2 cm were compared (hazard ratio (HR) 1.65, 95% CI 0.82 to 3.31; and HR 1.27, 95% CI 1.00 to 1.61, P = 0.05 for OS and PFS respectively).There was a high risk of bias due to the retrospective nature of these studies where, despite statistical adjustment for important prognostic factors, selection bias was still likely to be of particular concern.Adverse events, quality of life (QoL) and cost-effectiveness were not reported by treatment arm or to a satisfactory level in any of the studies.
AUTHORS' CONCLUSIONS: During primary surgery for advanced stage epithelial ovarian cancer all attempts should be made to achieve complete cytoreduction. When this is not achievable, the surgical goal should be optimal (< 1 cm) residual disease. Due to the high risk of bias in the current evidence, randomised controlled trials should be performed to determine whether it is the surgical intervention or patient-related and disease-related factors that are associated with the improved survival in these groups of women. The findings of this review that women with residual disease < 1 cm still do better than women with residual disease > 1 cm should prompt the surgical community to retain this category and consider re-defining it as 'near optimal' cytoreduction, reserving the term 'suboptimal' cytoreduction to cases where the residual disease is > 1 cm (optimal/near optimal/suboptimal instead of complete/optimal/suboptimal).
卵巢癌是女性中第六大常见癌症。除诊断和分期外，进行初次手术以实现最佳细胞减灭术（旨在切除大部分肿瘤的手术操作），因为残余肿瘤量是上皮性卵巢癌女性生存的最重要预后因素之一。对于许多妇科肿瘤医生而言，细胞减灭术的最佳结果仍是一个有争议的话题。妇科肿瘤学组（GOG）目前将“最佳”定义为最大直径每个残余肿瘤结节均为1厘米或更小，完全细胞减灭术（微小病灶）是理想的手术结果。尽管手术后残余肿瘤块的大小已被证明是晚期卵巢癌的重要预后因素，但尚不清楚是否是手术操作直接导致了与较少残余疾病相关的更好结果。
评估最佳初次细胞减灭术对手术分期为晚期上皮性卵巢癌（III期和IV期）女性的有效性和安全性。评估在0至2厘米范围内各种残余肿瘤大小对总生存期的影响。
我们检索了Cochrane对照试验中心注册库（CENTRAL）（《Cochrane图书馆》2010年第3期）以及Cochrane妇科癌症综述组试验注册库、MEDLINE和EMBASE（截至2010年8月）。我们还检索了临床试验注册库、科学会议摘要、纳入研究的参考文献列表并联系了该领域的专家。
来自随机对照试验（RCT）或前瞻性和回顾性观察性研究的关于残余疾病的回顾性数据，这些研究包括对100名或更多手术分期为晚期上皮性卵巢癌且接受初次细胞减灭术及随后铂类辅助化疗的成年女性进行的多变量分析。我们仅纳入将最佳细胞减灭术定义为导致最大直径任何阈值达2厘米的残余肿瘤的手术的研究。
两位综述作者独立提取数据并评估偏倚风险。在可能的情况下，数据在荟萃分析中进行综合。
未发现旨在评估手术作为晚期卵巢癌初次手术操作时有效性的RCT或前瞻性非RCT。我们发现11项回顾性研究进行了符合我们纳入标准的多变量分析。分析显示完全细胞减灭术的预后重要性，即残余疾病为微小病灶（即无可见疾病），因为这些女性组的总生存期（OS）和无进展生存期（PFS）显著延长。并非所有研究都报告了PFS，但有足够记录以得出明确结论。当我们比较次优（>1厘米）与最佳（<1厘米）细胞减灭术时，生存估计值降低，但对较低肿瘤量疾病组仍具有统计学显著优势。比较>2厘米和<2厘米的残余疾病时，OS无显著差异，PFS仅有临界差异（风险比（HR）1.65，95%置信区间0.82至3.31；HR 1.27，95%置信区间1.00至1.61，OS和PFS的P值分别为0.05）。由于这些研究的回顾性性质，存在较高的偏倚风险，尽管对重要预后因素进行了统计调整，但选择偏倚仍可能是特别需要关注的问题。治疗组未报告不良事件、生活质量（QoL）和成本效益，或者在任何研究中均未达到令人满意的水平。
在晚期上皮性卵巢癌的初次手术中，应尽一切努力实现完全细胞减灭术。当无法实现时，手术目标应为最佳（<1厘米）残余疾病。由于当前证据存在较高的偏倚风险，应进行随机对照试验以确定是手术干预还是患者相关及疾病相关因素与这些女性组生存率的提高相关。本综述的结果表明，残余疾病<1厘米的女性仍比残余疾病>1厘米的女性情况更好，这应促使外科界保留这一类别，并考虑将其重新定义为“接近最佳”细胞减灭术，将“次优”细胞减灭术这一术语保留用于残余疾病>1厘米的情况（最佳/接近最佳/次优而非完全/最佳/次优）。
