Prognostic significance and therapeutic potential of pyroptosis in gynecological malignancies.

This study aimed to evaluate the association between progestin and adipoQ receptor 3 (PAQR3) expression and survival outcomes, as well as disease progression, through a meta-analysis. A systematic literature search was conducted across multiple academic databases, including Cochrane Library, Embase, PubMed, Web of Science, and Google Scholar. Relevant studies were identified and screened based on predefined inclusion and exclusion criteria. Statistical analyses, including odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs), were employed to assess the relationship between PAQR3 expression levels and prognostic outcomes, as well as clinicopathological features in pan-cancer patients. A total of 1032 patients from nine eligible studies were included in the meta-analysis. The results demonstrated that high PAQR3 expression was significantly associated with improved overall survival (HR = 0.32; 95% CI = 0.19-0.56) and disease-free survival (HR = 0.35; 95% CI = 0.20-0.61) in pan-cancer patients. Downregulation of PAQR3 expression was significantly correlated with adverse clinicopathological characteristics, including lymph node metastasis (HR = 0.22; 95% CI = 0.06-0.82), higher histological grade (HR = 0.31; 95% CI = 0.12-0.81), advanced pathological stage (HR = 0.18; 95% CI = 0.05-0.66), tumor size (HR = 0.73; 95% CI = 0.36-1.5), distant metastasis (HR = 0.36; 95% CI = 0.07-1.82), and tumor invasion (HR = 0.18; 95% CI = 0.11-0.29). However, no significant associations were observed between PAQR3 expression and gender (HR = 0.94; 95% CI = 0.59-1.5) or age (HR = 1.10; 95% CI = 0.77-1.56). In conclusion, reduced PAQR3 expression in pan-cancer patients is associated with worse clinical outcomes and may promote cancer progression. These findings suggest that PAQR3 could serve as a potential prognostic biomarker and therapeutic target for cancer treatment.

Survival outcomes of robotic-assisted laparoscopy versus conventional laparoscopy and laparotomy for endometrial cancer: A systematic review and meta-analysis

Background: Dysregulation of long non-coding (lncRNA) has been reported in various solid tumors. HOXA cluster antisense RNA 2 (HOXA-AS2) is a newly identified lncRNA with abnormal expression in several human malignancies. However, its prognostic value remains controversial. This meta-analysis synthesized available data to clarify the association between HOXA-AS2 expression levels and clinical prognosis in multiple cancers.Methods: Four public databases (Embase, PubMed, Web of Science, The Cochrane Library) were used to identify eligible studies. Hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were combined to assess the correlation of HOXA-AS2 expression with survival outcomes and clinicopathological features of cancer patients. Publication bias was measured using Begg’s funnel plot and Egger’s regression test, and the stability of the combined results was measured using sensitivity analysis. Additionally, multiple public databases were screened and extracted to validate the results of this meta-analysis.Results: The study included 20 studies, containing 1331 patients. The meta-analysis showed that the overexpression of HOXA-AS2 was associated with poor overall survival (HR = 2.06, 95% CI 1.58–2.69, p < 0.001). In addition, the high expression of HOXA-AS2 could forecast advanced tumor stage (OR = 3.89, 95% CI 2.90–5.21, p < 0.001), earlier lymph node metastasis (OR = 3.48, 95% CI 2.29–5.29, p < 0.001), larger tumor size (OR = 2.36, 95% CI 1.52–3.66, p < 0.001) and earlier distant metastasis (OR = 3.54, 95% CI 2.00–6.28, p < 0.001). However, other clinicopathological features, including age (OR = 1.09, 95% CI 0.86–1.38, p = 0.467), gender (OR = 0.92, 95% CI 0.72–1.18, p = 0.496), depth of invasion (OR = 2.13, 95% CI 0.77–5.90, p = 0.146) and differentiation (OR = 1.02, 95% CI 0.65–1.59, p = 0.945) were not significantly different from HOXA-AS2 expression.Conclusion: Our study showed that the overexpression of HOXA-AS2 was related to poor overall survival and clinicopathological features. HOXA-AS2 may serve as a potential prognostic indicator and therapeutic target for tumor treatment.

Association between hospital treatment volume and survival of women with gynecologic malignancy: Japan Society of Obstetrics and Gynecology study

IgA nephropathy (IgAN) is an important cause of chronic renal failure, and nearly all patients with IgAN are at risk of developing to end-stage renal disease (ESRD) during their lifetime. This meta-analysis aimed to identify and evaluate risk factors associated with the progression of IgAN patients. Primary studies investigating the risk factors for predicting the progression of IgAN were included in this review. A comprehensive literature search was conducted across multiple electronic databases, including the Chinese Biological Medicine Database (CBM), China National Knowledge Infrastructure (CNKI), Cochrane Library, PubMed, Embase, Web of Science, and WANFANG, up to May 30, 2025. Two independent reviewers screened the literature based on the predefined inclusion and exclusion criteria, extracted the relevant data from the original studies, and assessed the quality of the included studies using the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed on at least two studies reporting on a specific outcome, with pooled effect sizes expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). Statistical analysis, including meta-analysis, subgroup analysis and sensitivity analysis, was conducted using the R software. Publication bias was evaluated using Egger's test in Stata12.0. A total of 53 studies, comprising 25,517 patients with IgAN, were included in the final analysis. This meta-analysis identified 10 clinical risk factors significantly associated with IgAN progression, including mean arterial pressure (MAP) (HR = 1.02, 95% CI: 1.01-1.03), diastolic blood pressure (DBP) (HR = 1.03, 95% CI: 1.01-1.05), systolic blood pressure (SBP) (HR = 1.03, 95% CI: 1.01-1.05), serum creatinine (SCr) (HR = 1.04, 95% CI: 1.03-1.06), triglyceride (HR = 1.11, 95% CI: 1.02-1.21), 24-h urinary protein excretion (UPE) (HR = 1.15, 95% CI: 1.12-1.18), low-density lipoprotein cholesterol (LDL-C) (HR = 1.37, 95% CI: 1.18-1.59), male sex (vs. female) (HR = 1.73, 95% CI: 1.16-2.59), complement C4 (C4) (HR = 1.81, 95% CI: 1.06-3.09), and hypertension (HR = 2.53, 95% CI: 1.92-3.33). The pathological features significantly predictive of IgAN progression including crescents (C1/C2) (vs. C0) (HR = 1.57, 95% CI: 1.24-1.99), C2 (vs. C0) (HR = 2.87, 95% CI: 1.65-5.01), endocapillary hypercellularity (E1) (vs. E0) (HR = 1.17, 95% CI: 1.02-1.35), segmental glomerulosclerosis (S1) (vs. S0) (HR = 2.23, 95% CI: 1.78-2.79), and tubular atrophy (T1/T2) (vs. T0) (HR = 5.12, 95% CI: 3.56-7.36), when analyzed individually, T1 (vs. T0) showed an HR = 4.59 (95% CI: 3.24-6.51), and T2 (vs. T0) showed an HR = 16.40 (95% CI: 9.65-27.87). In contrast, C1 (vs. C0) (HR = 1.41, 95% CI: 0.81-2.45) was not significantly associated with progression risk. Protective factors against lgAN progression included higher level of albumin (Alb) (HR = 0.95, 95% CI: 0.93-0.98), estimated glomerular filtration rate (eGFR) (HR = 0.96, 95% CI: 0.95-0.97), hemoglobin (Hb) (HR = 0.98, 95% CI: 0.97-0.99), complement C3 (C3) (HR = 0.97, 95% CI: 0.95-0.99). Additionally, female sex was associated with a lower risk of disease progression, with HR = 0.69 (95% CI: 0.57-0.84) and when compared directly with male HR = 0.55 (95% CI: 0.45-0.67). This meta-analysis indicates that MAP, DBP, SBP, SCr, triglyceride, 24-h UPE, LDL-C, male sex (vs. female), C4, hypertension, C-lesions, M-lesions, S-lesions, and T-lesions in Oxford classification are significantly associated with an increased risk of IgAN progression. In contrast, higher levels of Alb, eGFR, Hb, C3, as well as female sex (both as an independent variable and compared with males), are identified as protective factors in patients with IgAN.

A Nomogram for Predicting Progression-free Survival in Patients with Endometrial Cancer

There is no consensus on the correlation between human epididymis protein 4 (HE4) and prognosis of endometrial cancer (EC). Therefore, we performed a meta-analysis to assess the relationship between HE4 and prognosis of EC. In this systematic review and meta-analysis, the databases were searched. Correlation of serum or tissue HE4 with clinicopathological characteristics was determined by odds ratio (OR) or standardized mean difference (SMD) with 95% confidence interval (CI), respectively. The hazard ratio (HR) with 95% CI was calculated to evaluate the correlation between HE4 and survival outcome. A total of 38 published studies were eligible. We found that high levels of serum HE4 were associated with FIGO III-IV stage (SMD=1.58, 95%CI: 1.18-1.98, p < 0.001), grade 3 (SMD=0.66, 95%CI: 0.39-0.93, p=0.001), ≥50% myometrial invasion (SMD=0.78, 95%CI: 0.58-0.99, p < 0.001), lymphovascular space invasion (SMD=0.82, 95%CI: 0.54-1.11, p=0.001), lymph node metastasis (SMD=1.27, 95%CI: 0.84-1.69, p < 0.001), cervical involvement (SMD=0.71, 95%CI: 0.43-0.98, p=0.003), parametrial involvement (SMD=1.03, 95%CI: 0.71-1.35, p < 0.001) and peritoneal cytology (SMD=0.49, 95%CI: 0.22-0.75, p < 0.001). High expression of tissue HE4 was only significantly associated with lymph node metastasis (OR=6.19, 95%CI: 2.07-18.50, p=0.001). High levels of serum HE4 were significantly associated with poor overall survival (univariate: HR=3.77, 95%CI: 1.94-7.32, p < 0.001; multivariate: HR=2.15, 95%CI: 1.65-2.80, p < 0.001) and disease-free survival (univariate: HR=2.89, 95%CI: 2.14-3.88, p < 0.001; multivariate: HR=2.31, 95%CI:1.20-2.67, p < 0.001) in EC. Compared with cancer antigen 125, serum HE4 may be a better prognostic indicator for EC. High HE4 expression is associated with poor prognosis of EC and may be a potential prognostic biomarker for EC.

Background The association between tumour-infiltrating immune cells and the prognosis of endometrial cancer (EC) is controversial due to the smaller sample sizes and limited statistical power of the extant studies. We carried out a meta-analysis of the relationship between tumour-infiltrating immune cells and EC survival outcomes. Methods A literature search in multiple databases was carried out up to December 2019. Pooled hazard ratio (HRs) and 95% confidence intervals (CIs) were calculated by the Z-test to assess the association between infiltrating immune cells and overall survival (OS), progression-free survival (PFS), relapse-free survival (RFS), disease-specific survival (DSS), and disease-free survival (DFS). A subgroup analysis was performed based on the localisation of immune cells in tumour parenchyma or stroma, immune markers, and the International Federation of Gynecology and Obstetrics stage. Heterogeneity and publication bias between studies were evaluated by Cochran's Q-test and Egger regression test, respectively. Results Seventeen studies were included in the analysis. The pooled HR of OS, PFS, DSS, and DFS indicated that a high CD8+ T cell density was associated with a favorable prognosis in EC patients. A significant relationship was found between a high density of CD45RO+ T cells and a favorable OS in EC patients, but the FoxP3+ T cell density was not associated with either OS or RFS. A high TAM density was associated with a worse PFS. However, a sensitivity analysis indicated that the findings of PFS and DSS in CD8+ T cell and PFS in TAM were not robust results. Conclusion This is the first meta-analysis of the relationship between tumour-infiltrating immune cells and the prognosis of EC. High CD8+ and CD45RO+ T cell densities in tumours were associated with favorable outcomes in EC patients.

5509 Background: Sex hormone and insulin/insulin-like growth factor (IGF) axis signaling pathways play an important role in endometrial cancer development but their role in endometrial cancer recurrence is unknown. In this study GOG-8015 we evaluated these pathways in a prospective cohort of patients diagnosed with the most common type of endometrial cancer, endometrioid adenocarcinoma. Methods: Stage II-IV endometrioid endometrial adenocarcinoma patients (N = 816) enrolled in the GOG-210 study with pre-treatment specimens were tested for tumor mRNA and protein expression levels of IGF1, IGF2, IGF binding proteins ( IGFBP) -1and -3, the insulin (IR) and IGF-I receptors (IGF1R), and phosphorylated (activated) IR/IGF1R as well as estrogen (ER) and progesterone receptors (PR) using quantitative PCR and immunohistochemistry (IHC). Serum concentrations of insulin, IGF-I, IGFBP-3, estradiol, estrone and sex hormone binding globulin were measured using ELISAs. Hazard ratios (HR) and 95% confidence intervals (CI) for risk of recurrence were obtained from multivariable Cox proportional hazard’s models with adjustment for age, stage and grade. Results: Recurrence occurred in 280 (34%) cases during a mean of 5.4 years of follow-up. ER-positivity (HR 0.67, 95% CI 0.47-0.95), IR-positivity (HR 0.53, 95% CI 0.29-0.98) and serum IGF-I levels (highest versus lowest quartile, HR 0.66, 95% CI 0.47-0.92) were inversely associated with recurrence risk. Conversely, circulating estradiol (highest versus lowest tertile, HR 1.55, 95% CI 1.02-2.36) and insulin (per 10 uU/ml, HR 1.52, 95% CI 1.12-2.06) and phosphorylated IGF1R/pIR expression (HR 1.40, 95% CI 1.02-1.92) were associated with increased risk of recurrence. Conclusions: We identified novel sex hormone and insulin/IGF axis tissue and circulating biomarkers of recurrence in a prospective study of high stage endometrioid endometrial cancer. Circulating insulin and estradiol, and tissue phosphorylated (activated) IGR1R/IR were independently associated with recurrence. These findings support prioritizing studies to establish their clinical utility as prognostic biomarkers and to investigate new strategies that target these pathways for prevention and treatment of endometrial cancer recurrence.

Metabolic syndrome (MetS) is associated with a high risk of endometrial cancer (EC). However, its impact on EC progression remains unclear. This meta-analysis examined the association between MetS and survival outcomes in EC patients. A comprehensive search of PubMed, EMBASE, and Web of Science databases up to May 22, 2024, was conducted. Two independent reviewers performed study selection, data extraction, and quality assessment. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random effects model. Nine studies comprising 13,579 endometrial cancer (EC) patients were included. Among these, 2,896 patients (21.3%) had MetS at the time of enrollment. The follow-up durations ranged from 3.4 to 14.2 years. The results showed that EC patients with MetS at baseline demonstrated significantly poorer overall survival (HR = 1.57, 95% CI = 1.19-2.07, p = 0.002; I2 = 25%) and progression-free survival (HR = 1.33, 95% CI = 1.08-1.63, p = 0.007; I2 = 16%). A similar association was observed for cancer-specific survival (HR = 1.26, 95% CI = 1.10-1.44, p = 0.001; I2 = 0%). Subgroup analyses based on study characteristics showed consistent results across studies conducted in countries with different follow-up durations. This meta-analysis suggests that MetS is associated with poor survival outcomes in EC patients. Further prospective studies are required to validate our findings. PROSPERO, identifier CRD42024561654.

Gynecologic malignancies, such as cervical, endometrial, and ovarian cancers, are among the most prevalent and lethal cancers in women worldwide. Preclinical and epidemiological studies suggest that metformin may exert antitumor effects. However, its clinical efficacy in gynecologic malignancies remains uncertain. Hence, exploring the effects of metformin in prolonging progression-free survival (PFS) and overall survival (OS) in gynecological malignancies is crucial for guiding future clinical practice. This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to assess the effect of metformin combined with standard therapy on PFS and OS in individuals with gynecologic malignancies. Embase, the Cochrane Library, Web of Science, and PubMed were searched from database inception to 13 June 2025. RCTs meeting predefined PICOS criteria were included. Two investigators independently screened the studies, extracted data, and assessed the quality of eligible studies. Stata 15.1 was utilized to carry out meta-analyses, and random- or fixed-effects models were selected according to I2 values. Subgroup and sensitivity analyses were also performed. Five RCTs involving 705 patients were included. The overall analyses demonstrated that metformin combined with standard therapy did not significantly improve PFS (hazard ratio [HR] = 0.76, 95% confidence interval [CI]: 0.55-1.03, I2 = 36.1%) or OS (HR = 1.20, 95% CI: 0.88-1.62, I2 = 0.0%) compared with the control group. Subgroup analyses demonstrated no survival benefits in individuals with cervical or endometrial cancer. Only one study on ovarian cancer suggested that metformin might improve PFS (HR = 0.24, 95% CI: 0.09-0.65). However, the wide CI indicated limited reliability of the results. Sensitivity analyses confirmed the robustness of the findings. Current evidence from RCTs demonstrates that metformin combined with standard therapy can not significantly improve PFS or OS in individuals with gynecologic malignancies. Further larger, multicenter, long-term RCTs are warranted to evaluate the potential benefits of metformin in individuals with metabolic abnormalities and its combined use with novel therapies. https://www.crd.york.ac.uk/PROSPERO/, identifier, CRD2025105994.

In a PDS setting, there is moderate-certainty evidence that the amount of RD after primary surgery is a prognostic factor for overall and progression-free survival in women with advanced ovarian cancer. We separated our analysis into three distinct categories for the survival outcome including NMRD, SVRD and LVRD. After IDS, there may be only two categories required, although this is based on very low-certainty evidence, as all but one study included NMRD in the SVRD category. The one study that separated NMRD from SVRD showed no improved survival outcome in the SVRD category, compared to LVRD. Further low-certainty evidence also supported restricting to two categories, where women who had any amount of MRD after IDS had a significantly greater risk of death compared to women with NMRD. Therefore, the evidence presented in this review cannot conclude that using three categories applies in an IDS setting (very low-certainty evidence), as was supported for PDS (which has convincing moderate-certainty evidence).

e22544 Background: Lynch syndrome is the most common hereditary cause of colorectal and endometrial cancer. Non-genetic risk factors, including obesity, physical activity, alcohol intake, and smoking are well-established in sporadic cancers but are less studied in Lynch syndrome. A better understanding of these risk factors could directly contribute to cancer prevention. Methods: Searches were conducted on MEDLINE, Embase and Web of Science for retrospective or prospective cohort studies that investigated the association between modifiable risk factors and the risk of colorectal or endometrial cancer in people with Lynch syndrome. Screening, data extraction and quality assessment were completed by 2 reviewers independently. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) for colorectal and endometrial cancer were pooled using a random effects model. The protocol was prospectively registered on PROSPERO (CRD 42022378462) and the meta-analysis conducted in accordance with PRISMA and MOOSE reporting guidelines. Results: A total of 770 citations were reviewed. Twelve cohort studies involving 12685 patients with Lynch syndrome investigated risk of colorectal cancer, while 3 studies including 1865 patients assessed risk factors for endometrial cancer. Eight colorectal cancer studies were eligible for meta-analysis. Obesity (HR 2.38, 95% CI 1.52-3.73) and alcohol intake (HR 1.43, 95% CI 1.05-1.94) increased colorectal cancer risk, physical activity was protective (HR 0.66, 95% CI 0.52-0.83), and smoking had no effect (HR 1.02 95% CI 0.83-1.27). Type 2 diabetes mellitus and low dietary intake of calcium and multivitamins might increase risk of colorectal cancer, although more studies are needed. There is a paucity of data pertaining to endometrial cancer. In a qualitative synthesis of 3 endometrial cancer cohort studies, female hormonal risk factors and type 2 diabetes mellitus may affect the risk of endometrial cancer, but obesity was not associated with an increased risk. Conclusions: Lifestyle recommendations related to weight, physical activity, and alcohol may also be relevant to cancer prevention for individuals with Lynch syndrome and may provide a meaningful adjunct to standard interventions for risk modification. There are very poor data examining modifiable risk factors in endometrial cancer. Further high-quality prospective cohort studies, in particular including endometrial cancer as an endpoint, are needed to inform evidence-based cancer prevention strategies in this high-risk population.

A large number of studies have shown that high expression of vascular endothelial growth factor (VEGF) in cancer tissues is associated with poor prognosis of various cancers. However, this finding in endometrial cancer is controversial. Therefore, this meta-analysis aimed to explore the effects of VEGF on survival in patients with endometrial cancer. Four databases of PubMed, Medline, Web of Science, and China National Knowledge Infrastructure were searched to collect literature that met the inclusion criteria. The association between high VEGF expression and survival outcomes and clinicopathological features of patients with cancer was evaluated by calculating the combined hazard ratio (HR), odds ratio (OR), and 95% confidence interval (CI). The Begg test was used to assess publication bias. A total of 11 studies were included, involving 1251 patients. The results showed that compared with low VEGF expression, high VEGF expression was significantly associated with shorter overall survival (HR = 2.44, 95% CI = 1.15-5.16, I2 = 80%, P = .02) and disease-specific survival (HR = 7.87, 95% CI = 1.70-36.44, I2 = 64%, P = .008) but not with disease-free survival (HR = 1.45, 95% CI = 0.70-3.02, I2 = 68%, P = .32). In addition, VEGF expression is higher in patients with advanced stage (OR = 3.70, 95% CI = 2.22-6.19, P < .001), lower histological differentiation (OR = 2.08, 95% CI = 1.22-3.55, P = .007), and lymph node metastasis (OR = 5.42, 95% CI = 2.35-5.11, P < .001). High VEGF expression can predict poor prognosis and poor clinicopathological features in patients with endometrial cancer, and it may be a valuable new indicator to evaluate the prognosis of patients with endometrial cancer.

This is an updated version of the original Cochrane review published in Issue 2, 2007. The role of radiotherapy (both pelvic external beam radiotherapy (EBRT) and vaginal intracavity brachytherapy (VBT)) in stage I endometrial cancer following hysterectomy remains controversial. To assess the efficacy of adjuvant radiotherapy following surgery for stage I endometrial cancer. We searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Specialised Register to end-2005 for the original review, and extended the search to January 2012 for the update. We included randomised controlled trials (RCTs) that compared post-operative adjuvant radiotherapy (either EBRT or VBT, or both) versus no radiotherapy or VBT in women with stage I endometrial cancer. Two review authors independently assessed trials and extracted data to a specifically designed data collection form. The primary outcome was overall survival. Secondary outcomes were endometrial cancer-related deaths, locoregional recurrence and distant recurrence. Meta-analyses were performed using Cochrane Review Manager Software 5.1. We included eight trials. Seven trials (3628 women) compared EBRT with no EBRT (or VBT), and one trial (645 women) compared VBT with no additional treatment. We considered six of the eight trials to be of a high quality. Time-to-event data were not available for all trials and all outcomes.EBRT (with or without VBT) compared with no EBRT (or VBT alone) for stage I endometrial carcinoma significantly reduced locoregional recurrence (time-to-event data: five trials, 2965 women; Hazard Ratio (HR) 0.36, 95% Confidence Interval (CI) 0.25 to 0.52; and dichotomous data: seven trials, 3628 women; Risk Ratio (RR) 0.33, 95% CI 0.23 to 0.47). This reduced risk of locoregional recurrence did not translate into improved overall survival (time-to-event data: five trials, 2,965 women; HR 0.99, 95% CI 0.82 to 1.20; and dichotomous data: seven trials, 3628 women; RR 0.98, 95% CI 0.83 to 1.15) or improved endometrial cancer-related survival (time-to-event data: five trials, 2965 women; HR 0.96, 95% CI 0.72 to 1.28; and dichotomous data: seven trials, 3628 women; RR 1.02, 95% CI 0.81 to 1.29) or improved distant recurrence rates (dichotomous data: seven trials, 3628 women; RR 1.04, 95% CI 0.80 to1.35).EBRT did not improve survival outcomes in either the intermediate-risk or high-risk subgroups, although high-risk data were limited, and a benefit of EBRT for high-risk women could not be excluded. In the subgroup of low-risk patients (IA/B and grade 1/2), EBRT increased the risk of endometrial carcinoma-related deaths (including treatment-related deaths) (two trials, 517 women; RR 2.64, 95% CI 1.05 to 6.66) but there was a lack of data on overall survival. We considered the evidence for the low-risk subgroup to be of a low quality.EBRT was associated with significantly increased severe acute toxicity (two trials, 1328 patients, RR 4.68, 95% CI 1.35 to 16.16), increased severe late toxicity (six trials, 3501 women; RR 2.58, 95% CI 1.61 to 4.11) and significant reductions in quality of life scores and rectal and bladder function more than 10 years after randomisation (one trial, 351 women) compared with no EBRT.One trial of VBT versus no additional treatment in women with low-risk lesions reported a non-significant reduction in locoregional recurrence in the VBT group compared with the no additional treatment group (RR 0.39, (95% CI 0.14 to 1.09). There were no significant differences in survival outcomes in this trial. EBRT reduces the risk of locoregional recurrence but has no significant impact on cancer-related deaths or overall survival. It is associated with significant morbidity and a reduction in quality of life, and bladder and rectal function. EBRT may have an adverse effect on endometrial cancer survival when used to treat uncomplicated low-risk (IA/B grade 1/2) endometrial cancer. There is no demonstrable survival advantage from adjuvant EBRT for high-risk stage I endometrial cancer, however, the meta-analyses of this subgroup were underpowered and also included high-intermediate risk women. Further research is likely to have an important impact on our confidence in the estimates of effects and may change the estimates. Therefore, whilst there appears to be no survival benefit in the routine use of EBRT in women with stage I endometrial cancer, we cannot exclude a benefit in high-risk women. VBT is potentially useful in intermediate-risk and high-risk subgroups but evidence from further RCTs is needed. In addition, the definitions of risk should be standardised.