Neoadjuvant chemotherapy plus surgery versus surgery for cervical cancer

 

Abstract

Background

A prior systematic review found that giving neoadjuvant chemotherapy before surgery improved survival compared with radiotherapy. However, the role of neoadjuvant chemotherapy followed by surgery versus surgery alone is still unclear.

Objectives

To assess the role of neoadjuvant chemotherapy in women with early or locally advanced cervical cancer.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), (Issue 2, 2009), MEDLINE (to March 2009), LILACS (to March 2009), Physician's Data Query (PDQ) (to March 2009). Both published and unpublished trials were sought and systematic searches of a number of trial sources were undertaken with no restrictions.

Selection criteria

Randomised controlled trials (RCTs) comparing neoadjuvant chemotherapy with surgery in women with early or locally advanced cervical cancer who had not undergone any prior treatment likely to interfere with the treatment comparison. Trials giving radical radiotherapy for inoperable tumours and/or post-operative radiotherapy were also eligible. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), local and distant recurrence, rates of resection and surgical morbidity.

Data collection and analysis

Data were extracted from trial reports and independently checked by two review authors. Depending on the type of outcome, trial hazard ratios (HRs) and odds ratios (ORs) were obtained or estimated from trial reports or sought from trial investigators.

Main results

Six trials (1072 women) were identified for inclusion in the review. Although data on PFS was available for all six trials (1036 women), data on overall survival, resection rates and pathological response were only available for five trials (909 to 938 women) and data on recurrence were only available for three trials (604 women). Whilst PFS was significantly improved with neoadjuvant chemotherapy (HR = 0.76, 95% CI = 0.62 to 0.94, p = 0.01), no OS benefit was observed (HR = 0.85, 95% CI = 0.67 to 1.07, p = 0.17). Furthermore, estimates for both local (OR = 0.76, 95% CI = 0.49 to 1.17, p = 0.21) and distant (OR = 0.68, 95% CI = 0.41 to 1.13, p = 0.13) recurrence and rates of resection (OR = 1.55, 95% CI = 0.96 to 2.50, p = 0.07) only tended to be in favour of neoadjuvant chemotherapy, and heterogeneity was observed. Exploratory analyses of pathological response showed a significant decrease in adverse pathological findings with neoadjuvant chemotherapy (OR = 0.54, 95% CI = 0.39 to 0.73, p = < 0.0001 for lymph node status; OR = 0.58, 95% CI = 0.41 to 0.82, p = 0.002 for parametrial infiltration) which despite a high level of heterogeneity was still significant when the random effects model was used. There was also no difference in the effect of neoadjuvant chemotherapy according to total cisplatin dose, chemotherapy cycle length or by cervical cancer stage.

Authors' conclusions

Despite outcomes tending to be in favour of neoadjuvant chemotherapy few, including overall survival, were significant. Therefore, it remains unclear whether neoadjuvant chemotherapy consistently offers a benefit over surgery alone for women with early-stage or locally advanced cervical cancer.

 

Plain language summary

Chemotherapy given before surgery, compared with surgery alone for women with cervical cancer

Around the world, cervical cancer is the second most common cancer in women. Screening (with smear tests) has led to a decrease in the number of women with cervical cancer in some countries, but large numbers of women still die from the disease every year.

Where the cancer has not spread outside the cervix (early stage disease) women may have an operation to remove it by taking out the cervix, womb, the fallopian tubes, and maybe other nearby tissues (radical surgery). Or they might have treatment with x-rays from outside and inside the body (radical radiotherapy). Both of these treatments have been shown to be as good as each other. If the tumour is bigger, or has spread to tissues around the cervix (locally advanced disease) women may also get chemotherapy (drug treatment) at the same time as radiotherapy (chemoradiation).

Giving chemotherapy before radical surgery (neoadjuvant chemotherapy) might shrink the tumour. This could make surgery easier. It may also help to remove any tiny tumours that cannot be easily seen. A previous review found that women receiving chemotherapy before radical surgery lived longer than women who underwent radical radiotherapy. However, we don't know whether giving chemotherapy before radical surgery is better than radical surgery on its own.

This review was based on six trials that included 1072 women. Using the information available from the trials on the effects of chemotherapy, we found that giving chemotherapy before surgery helped women to live longer without cancer. It also seemed to help stop the disease from spreading. But it was not clear if chemotherapy made it easier to operate on the tumour. It was also not clear if chemotherapy helped to stop the cancer recurring, or if it helped women live longer in general. The type of drugs used or how they were given did not have any effect on the overall results. Also, results were similar in women with early stage and more advanced stages of disease.

In one of the trials, all women also recveived radiotherapy after surgery (post-operative radiotherapy). In the other trials, one third to two thirds of women got this post-operative radiotherapy. We are not sure how this extra treatment affects the results. It can also give women more side-effects.

Although neoadjuvant chemotherapy seems to have some effect on cervical cancer it is not clear that it helps women to live longer. However, if new drugs or new drug combinations are shown to have promising results, it may be worth doing more trials of neoadjuvant chemotherapy before surgery with these new treatments.

 

摘要

背景

新輔助性化療加手術與手術治療子宮頸癌的比較

先前一篇系統性文獻回顧發現,相較於放射治療，術前給予新輔助性化療可改善生存率。然而,相較於單純手術，手術前給予新輔助性化療，目前角色還不清楚。

目標

為了評估新輔助性化療在婦女的早期或晚期子宮頸癌的治療角色。

搜尋策略

我們檢索了Cochrane Central Register of Controlled Trials (CENTRAL), (Issue 2, 2009), MEDLINE (to March 2009), LILACS (to March 2009), Physician's Data Query (PDQ) (to March 2009) 。發表和未發表的試驗都一併搜尋，並系統性搜尋不少正在進行的試驗，沒有任何限制。

選擇標準

隨機對照試驗 (RCTs) 比較在尚未進行過任何治療的婦女早期或晚期子宮頸癌，新輔助性化療併手術是否可能干擾治療。針對不能手術根除的腫瘤給予放射治療和(或)術後放療等試驗也納入。主要結果是總體生存率 (OS) 。次要結果是無惡化生存率 (PFS), 局部復發和遠處復發,切除率和手術併發症。

資料收集與分析

經兩個審查作者獨立檢查，從試驗報告中摘錄數據。根據不同的結果型態,從試驗報告中或尋求試驗研究者協助，取得或估計hazard ratios (HRs) 和odds ratios (ORs) 。

主要結論

六項試驗 (1072女性) 被確認且列入審查。雖然所有六個試驗 (1036婦女) 都有提供PFS的數據,總生存率、手術切除率和病理反應只有5項試驗 (909 – 938名婦女) 提供，和只有3個試驗提供給復發率數據 (604婦女) 。雖然新輔助性化療有顯著PFS改善,(RR = 0.76, 95% CI 為0.62 – 0.94, p = 0.01), 沒有觀察到OS改善 (RR = 0.85, 95% CI 為0.67 – 1.07, p = 0.17) 。此外,估計局部復發 (OR = 0.76, 95% CI 為0.49 – 1.17, p = 0.21) 和遠處復發 (OR = 0.68, 95% CI 為0.41 – 1.13, p = 0.13), 切除率 (OR = 1.55, 95% CI 為0.96 – 2.50, p = 0.07) 皆傾向於採用新輔助性化療。探索性觀察分析病理反應顯示合併新輔助性化療方面，不利的病理結果大幅度下降 (淋巴結狀態OR 0.54, 95% CI 為0.39 – 0.73, p = <0.0001,子宮旁浸潤OR 0.58, 95% CI 為0.41 – 0.82, p = 0.002) ，雖然有一個高的異質性現象，應用隨機效應模型分析後仍然是有意義的。新輔助性化療效果上，依據總cisplatin劑量、化療週期的長度、或子宮頸癌的期別，這些並沒有差別。

作者結論

儘管結果趨於贊成新輔助性化療，但少數結果包括總體存活率是顯著的。因此，目前還不清楚是否新輔助性化療能持續提供早期或局部轉移性子宮頸癌婦女優於單純手術治療的益處。

翻譯人

本摘要由門諾醫院邱耀堃翻譯。

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

總結

手術加上術前化療與單純手術治療子宮頸癌的比較:子宮頸癌是全世界第二個最常見的婦女癌症。在一些國家，篩選 (抹片檢查) 使得婦女患子宮頸癌人數減少，但每年有大量的婦女仍死於這種疾病。在癌細胞還沒有擴散子宮頸外 (早期疾病) ，婦女可以接受手術將其子宮頸、子宮、輸卵管切除,或切除臨近其他組織 (根除術) 。或者,他們可以接受體外或體內Xray治療 (根治性放射治療) 。這兩種治療方法已被證明是一樣好。如果腫瘤較大,或已擴散到子宮頸周圍的組織 (局部晚期疾病) 的婦女也可以以化療治療 (藥物治療) 並同時接受放射治療 (放化療) 。根治術前給予化療 (新輔助性化療) 可能縮小腫瘤。這樣可以使手術更容易進行。它也可以有助於消除任何微小不容易看到的腫瘤。先前的研究發現,婦女在根治性手術前接受化療者，比根治性放射治療的女性壽命較長。但是,我們不確定是否在根治手術前給予化療優於單純根治性手術。此篇文獻回顧納入6個試驗,其中包括1072年婦女。從現有研究化療效果的試驗資料,我們發現,在手術前給予化療幫助婦女活得更長、無癌症復發。它似乎還有助於阻止疾病的蔓延。但目前還不清楚是否化療使得腫瘤切除更容易進行，也不清楚是否化療有助於阻止癌症復發,或者這是否能幫助婦女患者壽命更長。使用藥物的類型或如何給藥也不會影響最終結果。此外,不管婦女患者是初期或更晚期，都有類似的治療結果。其中一試驗中,所有的婦女患者於手術後接受放療 (手術後放射治療) 。在其他試驗中,三分之一到三分之二的婦女接受手術後放射治療。我們不確定這些額外的處理是會如何影響結果。它也可能給予婦女更多治療副作用。新輔助性化療似乎有助於子宮頸癌治療，但目前尚不清楚它是否幫助婦女活得更長。然而,假使新藥物或新的藥物組合都表現出有希望的成效,可能值得以這些新的治療方法進行更多術前新輔助性化療的試驗。