Adjuvant radiotherapy and chemoradiation after surgery for cervical cancer

 

Abstract

Background

There is an ongoing debate about the indications for, and value of, adjuvant pelvic radiotherapy after radical surgery in women with early cervical cancer. Certain combinations of pathologic risk factors are thought to represent sufficient risk for recurrence, that they justify the use of post-operative pelvic radiotherapy, though this has never been shown to improve overall survival, and use of more than one type of treatment (surgery and radiotherapy) increases the risks of side-effects and complications.

Objectives

To evaluate the effectiveness and safety of adjuvant therapies (radiotherapy, chemotherapy followed by radiotherapy, chemoradiation) after radical hysterectomy for early stage cervical cancer (FIGO stages IB1, IB2 or IIA).

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 4, 2008. The Cochrane Gynaecological Cancer Group Trials Register, MEDLINE (January 1950 to November 2008), EMBASE (1950 to November 2008). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field.

Selection criteria

Randomised controlled trials (RCTs) that compared adjuvant therapies (radiotherapy, chemotherapy followed by radiotherapy, or chemoradiation) with no radiotherapy or chemoradiation, in women with a confirmed histological diagnosis of early cervical cancer who had undergone radical hysterectomy and dissection of the pelvic lymph nodes.

Data collection and analysis

Two review authors independently abstracted data and assessed risk of bias. Information on grade three and four adverse events was collected from the trials. Results were pooled using random effects meta-analyses.

Main results

Two RCTs, which compared adjuvant radiotherapy with no adjuvant radiotherapy, met the inclusion criteria; they randomised and assessed 397 women. Meta-analysis of these two RCTs indicated no significant difference in survival at five years between women who received radiation and those who received no further treatment (Relative risk (RR) = 0.8, 95% Confidence interval (CI): 0.3 to 2.4). However, women who received radiation had a significantly lower risk of disease progression at five years (RR = 0.6, 95% CI 0.4 to 0.9).

Although the risk of serious adverse events was consistently higher if women received radiotherapy rather than no further treatment, these increased risks were not statistically significant, probably because the rate of adverse events was low.

Authors' conclusions

We found evidence, of moderate quality, that radiation decreases the risk of disease progression compared with no further treatment, but little evidence that it might improve overall survival. The evidence on serious adverse events was equivocal.

 

Plain language summary

Radiotherapy, or a combination of radiotherapy and chemotherapy, after surgery for early stage cervical cancer

At present, doctors are not sure whether women with early cervical cancer who have had their womb and pelvic lymph nodes removed should be given radiotherapy. If the woman has a combination of certain risk factors which put her at high risk of having a recurrence of her cancer, doctors often think that it would be a good idea to give her radiotherapy. However, radiotherapy has never been shown to improve overall survival for these women and the combination of surgery and radiotherapy increases the risk of side-effects and complications. We searched for all the available RCTs that assessed whether radiotherapy (with or without chemotherapy) could improve survival in these women.

We found only two trials that compared the use of radiotherapy with no radiotherapy in women with early cervical cancer who had their womb and pelvic lymph nodes removed and who were at risk of having a recurrence of their cancer. These two trials enrolled 397 women. When we combined the findings from these two trials, we found that, on average, women who received radiotherapy were between 40% and 90% less likely to have a relapse of their cancer within five years than women who did not. However, because of the low number of deaths in the trials, we could not confirm whether radiotherapy helped to prolong life: our best estimate was that, five years after treatment, women who received radiotherapy were about 20% more likely to be alive than those who did not, but this estimate may not be very accurate and women's actual prospects could be anywhere between being three times more likely to be alive and being 60% more likely to be dead.

Although women who had radiotherapy tended to have more complications than women who did not, we couldn't be sure whether this was due to chance rather than the radiotherapy because few women reported complications.

The main limitations of the review were that we did not find any trials that evaluated a combination of radiotherapy and chemotherapy and that the two trials of radiotherapy gave very little information about side effects.

 

摘要

背景

子宮頸癌手術之後輔以放射線治療和化學放射線治療

有關早期子宮頸癌婦女在根除式手術之後，輔以骨盆腔放射線治療的價值與適用性，一直都有所爭議。某些病理危險因子的組合被視為代表足夠的復發風險，基於避免這些復發風險而使用術後骨盆腔放射線治療，然而這從未顯示可以改善整體存活，而且使用一種以上的治療(手術和放射線治療)會增加副作用與併發症風險。

目標

評估早期子宮頸癌(FIGO分期IB1、IB2或IIA)患者在根除式子宮切除術之後，輔助治療(放射線治療、化療之後進行放射線治療、化學放射線治療)的效果與安全性。

搜尋策略

我們搜尋了Cochrane Central Register of Controlled Trials (CENTRAL)、Issue 4, 2008、Cochrane Gynaecological Cancer Group Trials Register、MEDLINE (1950年1月到2008年11月)、EMBASE (1950年到2008年11月)等資料庫。我們也搜尋臨床試驗登記資料、科學會議摘要、納入之研究的參考文獻，且和該領域的專家聯繫。

選擇標準

納入的隨機控制試驗(Randomised controlled trials (RCTs))為比較輔助治療(放射線治療、化療之後進行放射線治療、化學放射線治療)與沒有放射線治療或化學放射線治療，研究對象是組織診斷確認為早期子宮頸癌的婦女，接受了根除式子宮切除術且切除骨盆淋巴結。

資料收集與分析

2位回顧作者獨立摘錄資料與評估偏見風險。蒐集試驗中的等級3和4的副作用資料。使用隨機效果後設分析方式彙整所有結果。

主要結論

比較輔助放射線治療和沒有輔助放射線治療的2篇隨機控制試驗符合納入規範，總共隨機分派評估了397名婦女。這2篇隨機控制試驗的後設分析指出，接受放射線治療和未接受後續治療的婦女之間，5年存活率並無顯著差異(相對風險(Relative risk (RR)) = 0.8，95%信心區間(Confidence interval (CI)): 0.3−2.4)。不過，接受放射線治療的婦女在5年時之疾病惡化風險顯著較低(RR = 0.6，95% CI 0.4  0.9)。雖然接受放射線治療之婦女的嚴重副作用風險比起無後續治療者偏高，但這些差異未達統計上的顯著意義，或許是因為副作用比率低。

作者結論

我們發現，有中等品質之證據認為，相較於無後續治療，放射線輔助治療降低疾病惡化風險，但是改善整體存活的證據有限。有關嚴重副作用的證據尚有歧異。

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

早期子宮頸癌手術之後進行放射線治療、併用放射線治療和化療：目前，醫師們不確定早期子宮頸癌婦女移除子宮和淋巴結之後是否須給予放射線治療。如果這些婦女有合併某些危險因子造成癌症復發之風險較高，醫師們通常會認為需給她放射線治療。不過，放射線治療未曾顯示可改善這些婦女之整體存活率，且併用手術和放射線治療會增加副作用與併發症的風險。我們搜尋了目前所有評估放射線治療(併用或不併用化療)是否可以改善這些婦女之存活的隨機控制試驗，我們發現只有2篇試驗在有復發風險之早期子宮頸癌婦女移除子宮和骨盆淋巴結之後，比較使用和不使用放射線治療。這2篇試驗共納入397名婦女。彙整這2篇試驗的結果時，我們發現，平均而言，接受放射線治療的婦女有40% −90%在5年內比較不會復發癌症。不過，因為試驗中的死亡數很少，我們無法確認放射線治療是否可以延長生命：我們的最佳估計是，治療後5年，接受放射線治療的婦女約有20%比較可能存活，但是此估計可能沒有很準確，各地婦女的估計相當不同，存活可能達3倍或可能有60%比較容易死亡。雖然接受放射線治療的婦女比未接受者有更多併發症，我們無法確定這是否純屬機率、而非放射線治療所致，因為報告有併發症的婦女少。此回顧的主要限制是，我們無法找到任何評估併用放射線治療和化療的試驗，以及這2篇放射線治療試驗的副作用資料很少。