Abstract
RATIONALE: Radical hysterectomy is a standard operation for women with early-stage cervical cancer, involving removal of the womb, cervix (neck of the womb), surrounding tissues (parametrial tissue), and part of the vagina. Given a relatively low risk of parametrial involvement in a selected group of women with early-stage cervical cancer, simple hysterectomy (removing only the uterus and cervix) with pelvic lymphadenectomy (surgical removal of the lymph glands found in the pelvis) might be an alternative option to reduce risk of complications. OBJECTIVES: To determine the benefits and harms of simple hysterectomy with pelvic lymphadenectomy versus radical hysterectomy with pelvic lymphadenectomy for women with stage IA2-IB1 cervical cancer. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), Web of Science Core Collection, PubMed, and two trial registry databases, along with reference checking and citation searching. The last search date was 19 March 2025. ELIGIBILITY CRITERIA: We included randomised clinical trials comparing simple hysterectomy with pelvic lymphadenectomy versus radical hysterectomy with pelvic lymphadenectomy for women with cervical cancer FIGO 2019 stage IA2-IB1. OUTCOMES: Critical outcomes were all-cause mortality, overall survival (OS), cancer-related mortality, and disease-free survival (DFS). Important outcomes included cancer recurrence, adverse events, sexual dysfunction, cost-effectiveness, and quality of life (QoL). RISK OF BIAS: Two review authors independently assessed the risk of bias of each included study using the Cochrane Risk of bias 2 (RoB 2) tool. SYNTHESIS METHODS: We conducted meta-analyses using random-effects models to calculate hazard ratios (HRs), risk ratios (RRs), mean differences (MDs), and 95% confidence intervals (CIs) for all outcomes. We used GRADE to assess the certainty of evidence. INCLUDED STUDIES: We included two trials involving 740 participants. One small trial was conducted in Brazil (40 participants). The larger trial, involving 700 participants, included centres in Western Europe, South Korea, and Canada. In this larger trial, 75.0% of participants were white. We classified one report as awaiting classification, and did not identify any ongoing studies. SYNTHESIS OF RESULTS: Critical outcomes Low-certainty evidence revealed that simple hysterectomy may result in little or no difference in all-cause mortality (RR 1.12, 95% CI 0.44 to 2.89; I(2) = 0%, 2 studies, 740 participants), OS (HR 1.26, 95% CI 0.48 to 3.28; I(2) = 0%, 2 studies, 740 participants), and DFS (HR 1.01, 95% CI 0.48 to 2.11; I(2) = 53%, 2 studies, 740 participants) compared to radical hysterectomy. The evidence is very uncertain about the effect of simple hysterectomy on cancer-related mortality (RR 3.64, 95% CI 0.61 to 21.92; I(2) = 0%, 2 studies, 740 participants; very low-certainty evidence). Important outcomes Low-certainty evidence showed that simple hysterectomy may result in little or no difference regarding the rate of cancer recurrence compared to radical hysterectomy (RR 1.56, 95% CI 0.73 to 3.35; I(2) = 0%, 2 studies, 740 participants). Simple hysterectomy likely reduces the rate of adverse events compared to radical hysterectomy (RR 0.82, 95% CI 0.70 to 0.97; I(2) = 0%; 2 studies, 740 participants; moderate-certainty evidence). Sexual function and QoL outcomes appeared to be more favourable for women undergoing simple hysterectomy at some time points. Additionally, simple hysterectomy was the dominant strategy in terms of cost-effective assessment. We downgraded the certainty of the evidence primarily due to some concerns about risk in one included study, and due to imprecision of the pooled results. AUTHORS' CONCLUSIONS: Simple hysterectomy may be a viable option for carefully selected women with early-stage cervical cancer, as it may result in little to no differences in survival and cancer recurrence rates compared to radical hysterectomy. Additionally, there were likely fewer perioperative adverse events and there may be better short-term QoL and sexual function in women undergoing simple hysterectomy. The included studies did not directly compare the effect of the route of surgery (open versus minimal access). This review has a limited representation of non-white women and women from low-resource settings. FUNDING: No specific funding was received for this review. REGISTRATION: Cochrane protocol (2016) DOI: 10.1002/14651858.CD012335. PROSPERO 2016 CRD42016047631. Available from: crd.york.ac.uk/PROSPERO/view/CRD42016047631.