Coleridge Sarah L, Bryant Andrew, Kehoe Sean, Morrison Jo
Obstetrics and Gynaecology, Taunton and Somerset NHS Foundation Trust, Taunton, UK.
Institute of Health & Society, Newcastle University, Newcastle upon Tyne, UK.
Cochrane Database Syst Rev. 2021 Feb 5;2(2):CD005343. doi: 10.1002/14651858.CD005343.pub5.
Epithelial ovarian cancer presents at an advanced stage in the majority of women. These women require surgery and chemotherapy for optimal treatment. Conventional treatment has been to perform surgery first and then give chemotherapy. However, there may be advantages to using chemotherapy before surgery.
To assess whether there is an advantage to treating women with advanced epithelial ovarian cancer with chemotherapy before debulking surgery (neoadjuvant chemotherapy (NACT)) compared with conventional treatment where chemotherapy follows debulking surgery (primary debulking surgery (PDS)).
We searched the following databases on 11 February 2019: CENTRAL, Embase via Ovid, MEDLINE (Silver Platter/Ovid), PDQ and MetaRegister. We also checked the reference lists of relevant papers that were identified to search for further studies. The main investigators of relevant trials were contacted for further information.
Randomised controlled trials (RCTs) of women with advanced epithelial ovarian cancer (Federation of International Gynaecologists and Obstetricians (FIGO) stage III/IV) who were randomly allocated to treatment groups that compared platinum-based chemotherapy before cytoreductive surgery with platinum-based chemotherapy following cytoreductive surgery.
Two review authors independently extracted data and assessed risk of bias in each included trial.
We found 1952 potential titles, with a most recent search date of February 2019, of which five RCTs of varying quality and size met the inclusion criteria. These studies assessed a total of 1713 women with stage IIIc/IV ovarian cancer randomised to NACT followed by interval debulking surgery (IDS) or PDS followed by chemotherapy. We pooled results of the three studies where data were available and found little or no difference with regard to overall survival (OS) (1521 women; Hazard Ratio (HR) 0.95, 95% CI 0.84 to 1.07; I = 0%; moderate-certainty evidence) or progression-free survival in four trials where we were able to pool data (1631 women; HR 0.97, 95% CI 0.87 to 1.07; I = 0%; moderate-certainty evidence). Adverse events, surgical morbidity and quality of life (QoL) outcomes were poorly and incompletely reported across studies. There may be clinically meaningful differences in favour of NACT compared to PDS with regard to serious adverse effects (SAE grade 3+). These data suggest that NACT may reduce the risk of need for blood transfusion (risk ratio (RR) 0.80; 95% CI 0.64 to 0.99; four studies,1085 women; low-certainty evidence), venous thromboembolism (RR 0.28; 95% CI 0.09 to 0.90; four studies, 1490 women; low-certainty evidence), infection (RR 0.30; 95% CI 0.16 to 0.56; four studies, 1490 women; moderate-certainty evidence), compared to PDS. NACT probably reduces the need for stoma formation (RR 0.43, 95% CI 0.26 to 0.72; two studies, 581 women; moderate-certainty evidence) and bowel resection (RR 0.49, 95% CI 0.26 to 0.92; three studies, 1213 women; moderate-certainty evidence), as well as reducing postoperative mortality (RR 0.18; 95% CI 0.06 to 0.54:five studies, 1571 women; moderate-certainty evidence). QoL on the EORTC QLQ-C30 scale produced inconsistent and imprecise results in two studies (MD -1.34, 95% CI -2.36 to -0.32; participants = 307; very low-certainty evidence) and use of the QLQC-30 and QLQC-Ov28 in another study (MD 7.60, 95% CI 1.89 to 13.31; participants = 217; very low-certainty evidence) meant that little could be inferred.
AUTHORS' CONCLUSIONS: The available moderate-certainty evidence suggests there is little or no difference in primary survival outcomes between PDS and NACT. NACT may reduce the risk of serious adverse events, especially those around the time of surgery, and the need for bowel resection and stoma formation. These data will inform women and clinicians and allow treatment to be tailored to the person, taking into account surgical resectability, age, histology, stage and performance status. Data from an unpublished study and ongoing studies are awaited.
大多数上皮性卵巢癌女性患者就诊时已处于晚期。这些女性需要通过手术和化疗来获得最佳治疗效果。传统治疗方法是先进行手术，然后进行化疗。然而，术前使用化疗可能具有优势。
评估对于晚期上皮性卵巢癌女性患者，与手术后进行化疗的传统治疗方法（初次肿瘤细胞减灭术（PDS））相比，在肿瘤细胞减灭术前进行化疗（新辅助化疗（NACT））是否具有优势。
我们于2019年2月11日检索了以下数据库：Cochrane系统评价数据库、通过Ovid检索的Embase、MEDLINE（银盘/Ovid）、PDQ和MetaRegister。我们还检查了已识别的相关论文的参考文献列表，以寻找进一步的研究。联系了相关试验的主要研究者以获取更多信息。
针对晚期上皮性卵巢癌（国际妇产科联合会（FIGO）III/IV期）女性患者的随机对照试验（RCT），这些患者被随机分配至治疗组，比较了在肿瘤细胞减灭术前使用铂类化疗与肿瘤细胞减灭术后使用铂类化疗的效果。
两位综述作者独立提取数据，并评估每个纳入试验的偏倚风险。
我们共找到1952条潜在文献标题，最近的检索日期为2019年2月，其中五项质量和规模各异的RCT符合纳入标准。这些研究共评估了1713例IIIc/IV期卵巢癌女性患者，她们被随机分为接受NACT后行间隔性肿瘤细胞减灭术（IDS）组或PDS后行化疗组。我们汇总了三项有可用数据的研究结果，发现总体生存（OS）方面几乎没有差异（1521例女性；风险比（HR）0.95，95%置信区间0.84至1.07；I² = 0%；中等质量证据），在四项我们能够汇总数据的试验中，无进展生存方面也几乎没有差异（1631例女性；HR 0.97，95%置信区间0.87至1.07；I² = 0%；中等质量证据）。各研究中不良事件、手术并发症和生活质量（QoL）结果的报告较少且不完整。与PDS相比，NACT在严重不良反应（3级及以上）方面可能存在有利于NACT的具有临床意义的差异。这些数据表明，NACT可能降低输血需求风险（风险比（RR）0.80；95%置信区间0.64至0.99；四项研究，1085例女性；低质量证据）、静脉血栓栓塞风险（RR 0.28；95%置信区间0.09至0.90；四项研究，1490例女性；低质量证据）、感染风险（RR 0.30；95%置信区间0.16至0.56；四项研究，1490例女性；中等质量证据）。与PDS相比，NACT可能减少造口形成需求（RR 0.43，95%置信区间0.26至0.72；两项研究，581例女性；中等质量证据）和肠切除需求（RR 0.49，95%置信区间0.26至0.92；三项研究，1213例女性；中等质量证据），还可降低术后死亡率（RR 0.18；95%置信区间0.06至0.54：五项研究，1571例女性；中等质量证据）。在两项研究中，使用欧洲癌症研究与治疗组织生活质量核心问卷（EORTC QLQ - C30）量表得出的QoL结果不一致且不精确（平均差 - 1.34，95%置信区间 - 2.36至 - 0.32；参与者 = 307；极低质量证据），另一项研究中使用QLQ - C30和QLQ - C - Ov28得出的结果（平均差7.60，95%置信区间1.89至13.31；参与者 = 217；极低质量证据）意味着几乎无法得出结论。
现有中等质量证据表明，PDS和NACT在主要生存结局方面几乎没有差异。NACT可能降低严重不良事件的风险，尤其是手术前后的不良事件，以及肠切除和造口形成的需求。这些数据将为女性患者和临床医生提供参考，使治疗能够根据患者的手术可切除性、年龄、组织学类型、分期和体能状态进行个体化调整。有待未发表研究和正在进行研究的数据。
