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晚期卵巢癌:初次减瘤手术还是中间减瘤手术?基于随机试验结果和肿瘤生物学特性的五类患者:晚期卵巢癌的初次减瘤手术和中间减瘤手术

Advanced Ovarian Cancer: Primary or Interval Debulking? Five Categories of Patients in View of the Results of Randomized Trials and Tumor Biology: Primary Debulking Surgery and Interval Debulking Surgery for Advanced Ovarian Cancer.

作者信息

Makar Amin P, Tropé Claes G, Tummers Philippe, Denys Hannelore, Vandecasteele Katrien

机构信息

Department of Gynecologic Oncology, the Middelheim Hospital, Antwerpen, Belgium Department of Gynecologic Oncology, University Hospital of Ghent, Ghent, Belgium

Department of Gynecologic Oncology, The Norwegian Radium Hospital, Oslo, Norway.

出版信息

Oncologist. 2016 Jun;21(6):745-54. doi: 10.1634/theoncologist.2015-0239. Epub 2016 Mar 23.

Abstract

BACKGROUND

Standard treatment of stage III and IV advanced ovarian cancer (AOC) consists of primary debulking surgery (PDS) followed by chemotherapy. Since the publication of the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada trial, clinical practice has changed and many AOC patients are now treated with neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). The best option remains unclear. Ovarian cancer is a heterogenic disease. Should we use the diversity in biology of the tumor and patterns of tumor localization to better stratify patients between both approaches?

METHODS

This analysis was based on results of five phase III randomized controlled trials on PDS and IDS in AOC patients, three Cochrane reviews, and four meta-analyses.

RESULTS

There is still no evidence that NACT-IDS is superior to PDS. Clinical status, tumor biology, and chemosensitivity should be taken into account to individualize surgical approach. Nonserous (type 1) tumors with favorable prognosis are less chemosensitive, and omitting optimal PDS will lead to less favorable outcome. For patients with advanced serous ovarian cancer (type 2) associated with severe comorbidity or low performance status, NACT-IDS is the preferred option.

CONCLUSION

We propose stratifying AOC patients into five categories according to patterns of tumor spread (reflecting the biologic behavior), response to chemotherapy, and prognosis to make a more rational decision between PDS and NACT-IDS.

IMPLICATIONS FOR PRACTICE

Trial results regarding effect and timing of debulking surgery on survival of patients with advanced ovarian cancer have been inconsistent and hence difficult to interpret. This review examines all randomized trials on primary and interval debulking surgery in advanced ovarian cancer, including the results of the newly published CHORUS (chemotherapy or upfront surgery for newly diagnosed advanced ovarian cancer) trial. On the basis of findings presented in this review and in view of recent molecular data on the heterogeneity of ovarian tumors, we propose prognostic categorization for patients with advanced ovarian cancer to better distinguish those who would optimally benefit from primary debulking from those who would better benefit from interval debulking following neoadjuvant chemotherapy.

摘要

背景

晚期卵巢癌(AOC)Ⅲ期和Ⅳ期的标准治疗包括初始肿瘤细胞减灭术(PDS),随后进行化疗。自欧洲癌症研究与治疗组织/加拿大国立癌症研究所试验发表以来,临床实践发生了变化,现在许多AOC患者接受新辅助化疗(NACT),随后进行中间型肿瘤细胞减灭术(IDS)。最佳选择仍不明确。卵巢癌是一种异质性疾病。我们是否应该利用肿瘤生物学的多样性和肿瘤定位模式,以便在这两种治疗方法之间更好地对患者进行分层?

方法

本分析基于五项关于AOC患者PDS和IDS的Ⅲ期随机对照试验结果、三项Cochrane系统评价以及四项荟萃分析。

结果

仍然没有证据表明NACT-IDS优于PDS。应考虑临床状态、肿瘤生物学特性和化疗敏感性,以个体化手术方式。预后良好的非浆液性(1型)肿瘤对化疗的敏感性较低,省略最佳的PDS将导致较差的结果。对于合并严重合并症或体能状态较差的晚期浆液性卵巢癌(2型)患者,NACT-IDS是首选方案。

结论

我们建议根据肿瘤播散模式(反映生物学行为)、对化疗的反应和预后,将AOC患者分为五类,以便在PDS和NACT-IDS之间做出更合理的决策。

对实践的启示

关于肿瘤细胞减灭术对晚期卵巢癌患者生存的效果和时机的试验结果一直不一致,因此难以解释。本综述考察了所有关于晚期卵巢癌初始和中间型肿瘤细胞减灭术的随机试验,包括新发表的CHORUS(新诊断晚期卵巢癌的化疗或 upfront 手术)试验的结果。基于本综述中的研究结果,并鉴于最近关于卵巢肿瘤异质性的分子数据,我们建议对晚期卵巢癌患者进行预后分类,以便更好地区分那些最能从初始肿瘤细胞减灭术中获益的患者和那些在新辅助化疗后更能从中间型肿瘤细胞减灭术中获益的患者。

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