Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer

 

Abstract

Background

Epithelial ovarian cancer is diagnosed in 4500 women in the UK each year of whom 1700 will ultimately die of their disease. Ten to fifteen percent of all cases are diagnosed early when there is still a good possibility for cure. The treatment of early stage disease involves surgery to remove disease often followed by chemotherapy. The largest clinical trials of this adjuvant therapy show an overall survival (OS) advantage with adjuvant platinum based chemotherapy but the precise role of this treatment in sub-groups of patients with differing prognoses needs to be defined.

Objectives

To systematically review the evidence for adjuvant chemotherapy in early stage epithelial ovarian cancer to determine; firstly whether there is a survival advantage of this treatment over the policy of observation following surgery with chemotherapy reserved for treatment of disease recurrence, and secondly; to determine if clinical sub-groups of differing prognosis based on histological sub-type or completeness of surgical staging, have more or less to gain from chemotherapy following initial surgery.

Search methods

An electronic search was performed using the Cochrane Gynaecological Cancer Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2008), MEDLINE (1966 to 2008), EMBASE (1980 to 2008) and CancerLit. The search strategy was developed using free text and medical subject headings (MESH).

Selection criteria

The review authors selected those clinical trials that met the inclusion criteria set out based on the populations, interventions, comparisons and outcome measures.

Data collection and analysis

Two review authors independently extracted data and assessed trial quality. Disagreements were resolved by discussion with a third review author. Random effects meta-analyses and sub-group analyses were conducted.

Main results

Five randomised controlled trials (RCTs), enrolling 1277 women, with 46 to 110 months follow-up, met the inclusion criteria. These trials had low risk of bias. Meta-analysis of three trials with adequate data, assessing 1008 women, indicated that women who received adjuvant platinum-based chemotherapy had better overall survival (OS) than those who did not (hazard ratio (HR) 0.71; 95% CI 0.53 to 0.93). Likewise, meta-analysis of four trials with adequate data, assessing 1170 women, indicated that women who received adjuvant chemotherapy had better progression-free survival (PFS) than those who did not (HR 0.67; 95% CI 0.53 to 0.84). The trials included in these meta-analyses gave consistent estimates of the effects of chemotherapy.

Sub-group analysis suggested that women who had optimal surgical staging of their disease were unlikely to benefit from adjuvant chemotherapy (HR for OS 1.22; 95% CI 0.63 to 2.37) whereas those who had sub-optimal staging did (HR for OS 0.63; 95% CI 0.46 to 0.85). One trial showed a benefit from adjuvant chemotherapy among women at high risk (HR for OS 0.48; 95% CI 0.32 to 0.72) but not among those at low risk (HR for OS 0.95; 95% CI 0.54 to 1.66). However, these sub-group findings could be due to chance.

Authors' conclusions

Adjuvant platinum based chemotherapy is effective in prolonging the survival of the majority of patients who are assessed as having early stage epithelial ovarian cancer. However, even given the limits of sub-group analyses, there is strong evidence that optimal surgical staging identifies patients who have either little or nothing to gain from adjuvant chemotherapy. Taken together with the lack of a survival advantage seen in patients with "low-risk" cancers in the ICON1 trial, it appears safe to withhold adjuvant chemotherapy from optimally staged patients with well differentiated tumours.

 

Plain language summary

Post-surgery (adjuvant) chemotherapy for early stage epithelial ovarian cancer

Chemotherapy with platinum containing drugs given after surgery to remove ovarian cancers that have not spread beyond the pelvis saves lives but is probably unnecessary when the tumour is proven to have not spread outside of the ovary, particularly if the specific cell type is not aggressive.

 

摘要

背景

輔助性(手術後)化療使用在早期上皮性卵巢癌

在英國，有4500位婦女被診斷為上皮性卵巢癌症，每年1700人最終將因他們的疾病而過世。所有病例中的10～15％是在仍有治癒可能性的疾病早期被診斷出來的。早期卵巢癌的治療包含手術切除病灶，通常再加上化療。最大型的輔助性療法的臨床試驗顯示，以含鉑化療藥物作為輔助性療法，有利於整體病人的存活，但在不同預後結果的病人組群，這種療法的角色需要再確定。

目標

為了系統地回顧輔助性化療使用在早期卵巢癌的證據；首先，研究輔助化療相對於手術後觀察、待疾病復發再給予化療的治療策略而言，是否更有利於病人的存活；其次，利用組織學亞型或完整性手術分期為基準，取得不同預後的臨床分組，研究不同組別對於輔助化療的效果是否存有差異。

搜尋策略

我們搜尋了Cochrane Gynaecological Cancer Specialised Register、 Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2008)、MEDLINE (1966年到2008年)、 EMBASE (1966年到2008年) 和 CancerLit.等電子資料庫。以免費的文字和醫學主題詞(MESH)作為搜尋的策略。

選擇標準

本文作者選定符合收錄標準的臨床試驗，以人口、干預措施、比較項目和結果衡量作為收錄的標準。

資料收集與分析

由兩位作者獨立進行收納研究的數據摘錄和試驗方法品質的評估。由第3位作者解決雙方意見的分歧。資料進行了隨機效應統合分析和分組分析法。

主要結論

本回顧包含了1277位婦女，追蹤46至110個月，並符合收錄標準的5份隨機對照試驗。這些試驗具有偏差的風險都不高。統合分析3份具充分數據的試驗，評估1008位婦女，其結果顯示接受含鉑化療藥物作為輔助性化療的婦女，比沒有接受的，有較佳的整體病人的存活率(HR 0.71; 95% CI 0.53 to 0.93)。同樣，統合分析4份具充分數據的試驗，評估1170位婦女，其結果顯示接受輔助性化療的婦女，比那些沒有接受的，有較長的無疾病進展存活期(PFS)(HR 0.67; 95% CI 0.53 to 0.84) 。包含在統合分析中的幾個試驗，化療的效力預估都是前後一致的。分組分析顯示，婦女如接受了最完整的分期手術將不太可能從輔助性化療中獲益 (HR for OS 1.22; 95% CI 0.63 to 2.37)；然而，輔助化療法卻有利於那些接受次完整分期手術的婦女(HR for OS 0.63; 95% CI 0.46 to 0.85)。從1份試驗中顯示，輔助化療法有利於高危險群的婦女(針對整體存活率方面，HR 0.48; 95% CI 0.32 to 0.72)，但對於那些低危險群的婦女則沒有幫助(針對整體存活率方面，HR 0.95; 95% CI 0.54 to 1.66)，然而，這些分組結果可能是湊巧的。

作者結論

利用含鉑化療藥物作為輔助性化療，可以延長多數被診斷為早期上皮性卵巢癌的病人之存活時間。然而，即使是受分組分析的限制，仍有強烈的證據顯示，接受過完整手術分期的病人只能很少或根本無法受惠於輔助性化療，再參考ICON1試驗中�低風險�癌症病人同樣缺乏存活優勢，顯示對分化良好的腫瘤，在完整分期術後的患者不使用輔助性化療法似乎是安全的。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

手術後(輔助性)化療使用在早期上皮性卵巢癌:在手術移除未散佈到骨盆腔外的卵巢癌後，給予含鉑藥物的術後化療對於維持生命是有益的；，但是在確定腫瘤仍未散佈到卵巢外時，特別是在不那麼惡性的特殊細胞型態中就可能不需要這種方法。