What is the issue?
Cervical cancer arises from the neck of the womb (cervix). Worldwide, cervical cancer is the third most common cancer in women, with an estimated 570,000 new cases in 2018. The majority of the burden of the disease is in low- and middle-income countries (LMICs). As it mostly occurs in younger women (mostly 25 to 30 year-olds in the UK), the disease has significant adverse effects on women and the global socioeconomic situation as a whole.
Cervical cancer management is based on the spread of the cancer (stage of the disease) at the time of diagnosis. International Federation of Gynecology and Obstetrics (FIGO) staging classification describes disease as per spread, with stage IA1 disease as microscopic disease and stage IVB cancers as having spread to distant sites throughout the body. In stage IB3/II disease, the cancer is either quite large within the cervix or has already spread to immediately neighbouring tissues, without obviously involving more distant tissues or organs. Stage IB3/II disease is often termed as locally advanced cervical cancer.
In early stage disease, where a small tumour is confined to the cervix, surgical treatment (removal of uterus (womb) and pelvic lymph nodes) will cure the vast majority of women. However, when cervical cancer spreads to adjacent tissues or organs, surgery is unlikely to be curative and so, instead of surgery, radiotherapy is offered in combination with weekly chemotherapy (chemoradiotherapy). Although chemoradiotherapy is able to cure the majority of women with locally advanced cervical cancer, nearly a quarter will have residual cancer within their cervix.
If there is residual (remaining) disease in the cervix after chemoradiotherapy, options include a 'simple' hysterectomy (surgery to remove the womb and cervix), a radical hysterectomy (hysterectomy including removal of a cuff of vagina and parametrial tissue (tissues surrounding the cervix)), or exenterative surgery (which involves removal of the womb, cervix, vagina and parametrial tissue together with removal of the bladder and/or bowel and formation of stomas to divert urine or bowel contents). Surgery following radiotherapy is more complex and has a higher risk of complications due to scarring and loss of tissue perfusion.
This group of women might benefit from hysterectomy prior to chemoradiotherapy to reduce the volume of their disease and improve their chance of cure. However, studies comparing outcomes of radical hysterectomy and pelvic lymph node dissection and/or pelvic chemoradiotherapy in early stage disease show that combination treatment does not improve survival and those who had both radical surgery and radiotherapy/chemoradiotherapy had worse side effects. A more limited hysterectomy might debulk the cancer prior to chemoradiotherapy and improve survival rates without having a significant impact on quality of life. However, surgery prior to chemoradiotherapy would subject the three-quarters of women, who would not benefit from surgery, to the additional risks of major surgery. Surgery first would also delay the onset of chemoradiotherapy, which might reduce the chance of success of otherwise curative treatment, and thereby, lower survival rates.
We wanted to evaluate the evidence for the role of planned debulking hysterectomy followed by chemoradiotherapy compared to chemoradiotherapy alone in women with locally advanced cervical cancer.
What did we do?
e searched the scientific literature over 75 years (from 1946 to 12 April 2021) for randomised controlled trials (RCTs) and non-randomised studies (NRSs) that compared debulking hysterectomy prior to chemoradiotherapy compared to chemoradiotherapy alone in women with locally advanced cancer of the cervix.
What did we find?
We found no studies for or against the effectiveness of debulking hysterectomy followed by chemoradiotherapy compared to chemoradiotherapy alone in women with locally advanced cancer of the cervix.
Our conclusions
There is no evidence for the role of debulking hysterectomy followed by chemoradiotherapy compared to chemoradiotherapy alone in women with locally advanced cancer of the cervix.
There was no evidence for or against debulking hysterectomy followed by CCRT versus CCRT alone for FIGO (2019) stage IB3/II cervical cancer.
With an estimated 570,000 new cases reported globally in 2018, and increasing numbers of new cases in countries without established human papillomavirus (HPV) vaccination programmes, cervical cancer is the third most common cancer in women worldwide. The majority of global disease burden (around 85%) is in low-and middle-income countries (LMICs), with estimates of cervical cancer being the second most common cancer in women in such regions. As it commonly affects younger women, cervical cancer has the greatest impact on years of life lost (YLL) and adverse socioeconomic outcomes compared to all other cancers in women. Management of cervical cancer depends on tumour stage.
Radical hysterectomy with lymphadenectomy is the standard primary treatment modality for International Federation of Gynecology and Obstetrics (FIGO) stage (2019) 1B1 to 1B3 disease. However, for larger primary tumours, radical hysterectomy is less commonly recommended. This is mainly due to a high incidence of unfavourable histopathological parameters, which require adjuvant concurrent chemoradiotherapy (CCRT) (chemotherapy given with radiotherapy treatment). CCRT is the standard of care and is widely used as first-line treatment for cervical cancer considered to be not curable with surgery alone (i.e.those with locally advanced disease). However, a sizable cohort of women managed with primary CCRT will have residual disease within the cervix following treatment.
Debulking' hysterectomy to remove (debulk) the primary tumour in locally advanced disease, prior to CCRT, may be an alternative management strategy, avoiding the potential need for surgery for residual cervical disease following CCRT, which may be more extensive, or have increased morbidity due to CCRT. However, this strategy may subject more women to unnecessary surgery and its inherent risks.
To assess the efficacy and harms of debulking hysterectomy (simple or radical) followed by chemoradiotherapy (CCRT) versus CCRT alone for FIGO (2019) stage IB3/II cervical cancer.
We systematically searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 4), MEDLINE via Ovid (1946 to 12 April 2021) and Embase via Ovid (1980 to 12 April 2021). We also searched other registers of clinical trials, abstracts of scientific meetings and reference lists up to 12 April 2021.
We searched for randomised controlled trials (RCTs), quasi-RCTs or non-randomised studies (NRSs) comparing debulking hysterectomy followed by CCRT versus CCRT alone for locally advanced FIGO (2019) stage IB3/II cervical malignancy.
We applied Cochrane methodology, with two review authors independently assessing whether potentially relevant studies met the inclusion criteria. We planned to apply standard Cochrane methodological procedures to analyse data and risk of bias.
We did not find any evidence for or against debulking hysterectomy followed by CCRT versus CCRT alone for FIGO (2019) stage IB3/II cervical cancer. We did not identify any studies assessing the validity of debulking hysterectomy for these women.