Background Laparoscopic hysterectomy is accepted worldwide as the standard treatment option for early-stage endometrial cancer. However, there are limited data on long-term survival, particularly... Show moreBackground Laparoscopic hysterectomy is accepted worldwide as the standard treatment option for early-stage endometrial cancer. However, there are limited data on long-term survival, particularly when no lymphadenectomy is performed. We compared the survival outcomes of total laparoscopic hysterectomy (TLH) and total abdominal hysterectomy (TAH), both without lymphadenectomy, for early-stage endometrial cancer up to 5 years postoperatively.MethodsFollow-up of a multi-centre, randomised controlled trial comparing TLH and TAH, without routine lymphadenectomy, for women with stage I endometrial cancer. Enrolment was between 2007 and 2009 by 2:1 randomisation to TLH or TAH. Outcomes were disease-free survival (DFS), overall survival (OS), disease-specific survival (DSS), and primary site of recurrence. Multivariable Cox regression analyses were adjusted for age, stage, grade, and radiotherapy with adjusted hazard ratios (aHR) and 95% confidence intervals (95%CI) reported. To test for significance, non-inferiority margins were defined.ResultsIn total, 279 women underwent a surgical procedure, of whom 263 (94%) had follow-up data. For the TLH (n = 175) and TAH (n = 88) groups, DFS (90.3% vs 84.1%; aHR[recurrence], 0.69; 95%CI, 0.31–1.52), OS (89.2% vs 82.8%; aHR[death], 0.60; 95%CI, 0.30–1.19), and DSS (95.0% vs 89.8%; aHR[death], 0.62; 95%CI, 0.23–1.70) were reported at 5 years. At a 10% significance level, and with a non-inferiority margin of 0.20, the null hypothesis of inferiority was rejected for all three outcomes. There were no port-site or wound metastases, and local recurrence rates were comparable.ConclusionDisease recurrence and 5-year survival rates were comparable between the TLH and TAH groups and comparable to studies with lymphadenectomy, supporting the widespread use of TLH without lymphadenectomy as the primary treatment for early-stage, low-grade endometrial cancer. Show less
The septate uterus has an estimated prevalence of 0.2% to 2.3% in women of reproductive age and is associated with impaired reproductive outcomes, the biologic basis of which is unclear. The... Show moreThe septate uterus has an estimated prevalence of 0.2% to 2.3% in women of reproductive age and is associated with impaired reproductive outcomes, the biologic basis of which is unclear. The standard-of-care treatment for septate uterus is hysteroscopic septum resection. The evidence base for this procedure entails observational studies and nonrandomized comparative studies, resulting in relatively low-quality evidence and conflicting professional society guidelines.This large, multicenter cohort study aimed to determine whether hysteroscopic septum resection improves reproductive outcomes compared with expectant management in women with a septate uterus who wish to conceive. Data on women with septate uterus between January 2000 and August 2018 were obtained from 18 centers in the Netherlands, 2 centers in the United States, and 1 center in the United Kingdom. Additionally, women declining participation in a separate 2015 randomized controlled trial examining differences between septum resection and expectant management were invited for participation prospectively. Data involving baseline characteristics, treatment, and pregnancies that occurred prior to identification of septate uterus (OB history) and following septate uterus diagnosis (follow-up) were obtained via medical record. Septate uterus was defined by the treating physician and ascertained with hysterosalpinography, 3D ultrasound, MRI, saline or gel infusion sonohysterography, or hysteroscopy combined with laparoscopy. The primary outcome measurement was live birth, and secondary outcomes included ongoing pregnancy, early pregnancy loss, preterm birth, and fetal malpresentation. Comparative analysis between septum resection and expectant management arms involved only the first live birth or ongoing pregnancy in follow-up. Cox proportional regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for differences in live birth and ongoing pregnancy rate between women in the 2 arms while accounting for follow-up time.A total of 257 women were confirmed eligible and included in the study for analysis, of which 151 underwent septum resection, and 106 underwent expectant management. In women who underwent resection compared with expectant management, a lower proportion was of White origin, more women had a history of subfertility, a lesser percentage had previous live birth (16.6% vs 36.8%, P < 0.001), and ascertainment of the septate uterus was significantly different (P < 0.001). Themedian duration of follow-up was 46 months, and 53% of women who had septum resection had at least 1 live birth compared with 71.7% who had expectant management (HR, 0.71; 95% CI, 0.49-1.02). There was no significant difference in cumulative live birth between the groups. When restricting analysis to 1 year following septate uterus diagnosis, 32 women who underwent resection had a live birth (21.2%) compared with 36 women who underwent expectant management (37.1%) (HR, 0.45; 95% CI, 0.27-0.75). Womenwith 1 or more previous pregnancy losses undergoing septumresection were found to have an increased risk of pregnancy loss compared with women who had expectant management (OR, 2.65; 95% CI, 1.05-6.67).This multicenter cohort study demonstrates that more than 50% of women with a septate uterus who wish to conceive had a live birth. The results show that septum resection does not lead to improved birth outcomes or a decrease in risk of pregnancy loss or preterm birth compared with expectant management in these women. Show less
STUDY QUESTION: Does septum resection improve reproductive outcomes in women with a septate uterus?SUMMARY ANSWER: In women with a septate uterus, septum resection does not increase live birth rate... Show moreSTUDY QUESTION: Does septum resection improve reproductive outcomes in women with a septate uterus?SUMMARY ANSWER: In women with a septate uterus, septum resection does not increase live birth rate nor does it decrease the rates of pregnancy loss or preterm birth, compared with expectant management.WHAT IS KNOWN ALREADY: The septate uterus is the most common uterine anomaly with an estimated prevalence of 0.2-2.3% in women of reproductive age, depending on the classification system. The definition of the septate uterus has been a long-lasting and ongoing subject of debate, and currently two classification systems are used worldwide. Women with a septate uterus may be at increased risk of subfertility, pregnancy loss, preterm birth and foetal malpresentation. Based on low quality evidence, current guidelines recommend removal of the intrauterine septum or, more cautiously, state that the procedure should be evaluated in future studies.STUDY DESIGN, SIZE, DURATION: We performed an international multicentre cohort study in which we identified women mainly retrospectively by searching in electronic patient files, medical records and databases within the time frame of January 2000 until August 2018. Searching of the databases, files and records took place between January 2016 and July 2018. By doing so, we collected data on 257 women with a septate uterus in 21 centres in the Netherlands, USA and UK.PARTICIPANTS/MATERIALS, SETTING, METHODS: We included women with a septate uterus, defined by the treating physician, according to the classification system at that time. The women were ascertained among those with a history of subfertility, pregnancy loss, preterm birth or foetal malpresentation or during a routine diagnostic procedure. Allocation to septum resection or expectant management was dependent on the reproductive history and severity of the disease. We excluded women who did not have a wish to conceive at time of diagnosis. The primary outcome was live birth. Secondary outcomes included pregnancy loss, preterm birth and foetal malpresentation. All conceptions during follow-up were registered but for the comparative analyses, only the first live birth or ongoing pregnancy was included. To evaluate differences in live birth and ongoing pregnancy, we used Cox proportional regression to calculate hazard rates (HRs) and 95% CI. To evaluate differences in pregnancy loss, preterm birth and foetal malpresentation, we used logistic regression to calculate odds ratios (OR) with corresponding 95% CI. We adjusted all reproductive outcomes for possible confounders.MAIN RESULTS AND THE ROLE OF CHANCE: In total, 257 women were included in the cohort. Of these, 151 women underwent a septum resection and 106 women had expectant management. The median follow-up time was 46 months. During this time, live birth occurred in 80 women following a septum resection (53.0%) compared to 76 women following expectant management (71.7%) (HR 0.71 95% CI 0.49-1.02) and ongoing pregnancy occurred in 89 women who underwent septum resection (58.9%), compared to 80 women who had expectant management (75.5%) (HR 0.74 (95% CI 0.52-1.06)). Pregnancy loss occurred in 51 women who underwent septum resection (46.8%) versus 31 women who had expectant management (34.4%) (OR 1.58 (0.81-3.09)), while preterm birth occurred in 26 women who underwent septum resection (29.2%) versus 13 women who had expectant management (16.7%) (OR 1.26 (95% CI 0.52-3.04)) and foetal malpresentation occurred in 17 women who underwent septum resection (19.1%) versus 27 women who had expectant management (34.6%) (OR 0.56 (95% CI 0.24-1.33)).LIMITATIONS, REASONS FOR CAUTION: Our retrospective study has a less robust design compared with a randomized controlled trial. Over the years, the ideas about the definition of the septate uterus has changed, but since the 257 women with a septate uterus included in this study had been diagnosed by their treating physician according to the leading classification system at that time, the data of this study reflect the daily practice of recent decades. Despite correcting for the most relevant patient characteristics, our estimates might not be free of residual confounding.WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that septum resection, a procedure that is widely offered and associated with financial costs for society, healthcare systems or individuals, does not lead to improved reproductive outcomes compared to expectant management for women with a septate uterus. The results of this study need to be confirmed in randomized clinical trials. Show less
