Treatment of cervical cancers that are larger than 4 cm still thought to be confined to the cervix (classified as stage IB2 cervical cancer) is controversial. Some clinicians believe that a combination of radiotherapy (high-energy rays) and chemotherapy (anti-cancer drugs), together known as chemoradiotherapy or chemoradiation, is better when the tumours are larger than 4 cm. This is based on the argument that the chance of the cancer returning after surgery is high, therefore most women will need chemoradiotherapy, even if they have surgery initially. The other school of thought is that these tumours are so large that they do not respond well to chemoradiotherapy and women with this stage of cervical cancer would benefit from surgery despite being at high risk of needing chemoradiotherapy after surgery. However, there are concerns about toxicity and complications related to the use of both surgery and chemoradiotherapy in women with cervical cancer, as receiving both treatments can increase morbidity. Therefore, many centres have moved towards providing only chemoradiotherapy. As there remains uncertainty about which treatment (surgery or chemoradiotherapy) is better for women with stage IB2 cervical cancer, we conducted this systematic review to try and answer this question.
How we conducted the review
We searched for evidence that compared chemoradiotherapy to surgery (type II or type III radical hysterectomy with bilateral pelvic lymphadenectomy) from 1946 to April 2018. We searched for both randomised controlled trials (where people taking part are put into groups at random) and non-randomised studies (in which a defined group of people (the cohort) are followed over time).
What we found
We only found one non-randomised study that compared surgery with chemoradiotherapy, but this study combined data on stages IB2 to IIA. Although it met the inclusion criteria, we could not analyse the data as we could not extract data specific to stage IB2 cervical cancers, therefore we considered the findings of this study to be uncertain with respect to our review question.
At present, there is no high-certainty evidence to inform us of which of the current treatment options (chemoradiotherapy or radical surgery) is better for stage IB2 cervical cancer. Women with stage IB2 cervical cancer should be counselled regarding this uncertainty and potential side effects, and the choice of treatment should take into account the availability of the treatments in a particular health resource and patient preference.
Ideally, a large multicentred trial is needed to determine which of the two treatments are better for treating women with stage IB2 cervical cancer. However, because of the relative rarity of stage 1B2 cancer, and the potential complications resulting from combining surgery and chemoradiotherapy, clinicians might continue to treat most women with chemoradiotherapy, and trials in this field might not be feasible.
There is an absence of high-certainty evidence on the relative benefits and harms of primary radical hysterectomy versus primary chemoradiotherapy for stage IB2 cervical cancer. More research is needed on the different treatment options in stage IB2 cervical cancer, particularly with respect to survival, adverse effects, and quality of life to facilitate informed decision-making and individualised care.
Cervical cancer is the fourth most common cancer in women, with 528,000 estimated new cases globally in 2012. A large majority (around 85%) of the disease burden occurs in low- and middle-income countries (LMICs), where it accounts for almost 12% of all female cancers. Treatment of stage IB2 cervical cancers, which sit between early and advanced disease, is controversial. Some centres prefer to treat these cancers by radical hysterectomy, with chemoradiotherapy reserved for those at high risk of recurrence. In the UK, we treat stage IB2 cervical cancers mainly with chemoradiotherapy, based on the rationale that a high percentage will have risk factors necessitating chemoradiotherapy postsurgery. There has been no systematic review to determine the best possible evidence in managing these cancers.
To determine if primary surgery for stage IB2 cervical cancer (type II or type III radical hysterectomy with lymphadenectomy) improves survival compared to primary chemoradiotherapy.
To determine if primary surgery combined with postoperative adjuvant chemoradiotherapy, for stage IB2 cervical cancer increases patient morbidity in the management of stage IB2 cervical cancer compared to primary chemoradiotherapy.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 3), MEDLINE via Ovid (1946 to April week 2, 2018) and Embase via Ovid (1980 to 2018 week 16). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies up to April 2018.
We searched for randomised controlled trials (RCTs), quasi-RCTs or non-randomised studies (NRSs) comparing surgery to chemoradiotherapy in stage IB2 cervical cancers.
Two review authors independently assessed whether potentially relevant studies met the inclusion criteria, abstracted data, assessed risk of bias and analysed data using standard methodological procedures expected by Cochrane.
We identified 4968 records from the literature searches, but we did not identify any RCTs that compared primary surgery with chemoradiotherapy in stage IB2 cervical cancer.
We found one NRS comparing surgery to chemoradiotherapy in IB2 and IIA2 cervical cancers which met the inclusion criteria. However, we were unable to obtain data for stage IB2 cancers only and considered the findings very uncertain due to a high risk of selection bias.