Maria-Eulalia Fernandez-Montoli

Fertility-Sparing Treatment for Atypical Endometrial Hyperplasia and Endometrial Cancer: A Cochrane Systematic Review Protocol

Endometrial cancer is the fifth most common cancer in women and atypical endometrial hyperplasia is a precancerous lesion. Obesity is an important risk factor for endometrioid endometrial adenocarcinoma and endometrial hyperplasia. Progesterone is recommended as first-line treatment in endometrial cancer or atypical endometrial hyperplasia in women who wish to preserve fertility, but optimal treatment schedules have not been defined. Metformin or bariatric surgery may also be useful in these women. The effectiveness and safety of fertility-preserving treatments being used for women with atypical endometrial hyperplasia and stage IA grade 1 endometrial cancer is unclear. Therefore, the systematic review aims to determine this point. We will search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, trial registers, conference proceedings, abstracts, cooperative trial groups and reference lists. We will include randomised controlled trials (RCTs) that compare fertility-preserving therapy including orally administered progesterone versus a levonorgestrel-releasing intrauterine system (IUS), metformin, other pharmacological interventions or bariatric surgery, and any of these interventions with womb-removing surgery. Quasi-randomised trials, non-randomised trials and cohort studies will be included. Two review authors will independently assess study eligibility and risk of bias and extract data. The primary outcomes are complete pathologic response and live birth rate. Secondary outcomes include overall survival, progression-free survival, pregnancy rate, need for hysterectomy, adverse events, psychological symptoms and quality of life. This review aims to clarify the effectiveness and risks of fertility-preserving treatments, including complete pathologic response rate, live birth rates, need for surgical treatment, adverse events, psychological symptoms and quality of life. The broad scope of the review includes the use of progesterone, metformin to reverse insulin resistance, and bariatric surgery or operative hysteroscopy. The results may help to determine the optimal fertility-sparing treatment in endometrial cancer and atypical endometrial hyperplasia. Prospero 2019 number CRD42019145991.

Long‐term predictors of residual or recurrent cervical intraepithelial neoplasia 2–3 after treatment with a large loop excision of the transformation zone: a retrospective study

ObjectiveTo assess the long‐term risk factors predicting residual/recurrent cervical intraepithelial neoplasia (CIN 2–3) and time to recurrence after large loop excision of the transformation zone (LLETZ).DesignRetrospective study.SettingColposcopy clinic.Population242 women with CIN 2–3 treated between 1996 and 2006 and followed up until June 2016.MethodsAge, margins, and high‐risk human papillomavirus (HR‐HPV) were estimated using Cox proportional hazard and unconditional logistic regression models. The cumulative probability of treatment failure was estimated by Kaplan–Meier analysis.Main outcome measureHistologically confirmed CIN 2–3, HR‐HPV, margins, age.ResultsCIN 2–3 was associated with HR‐HPV (HR = 30.5, 95% confidence interval [CI] = 3.80–246.20), age >35 years (HR = 5.53, 95% CI = 1.22–25.13), and margins (HR = 7.31, 95% CI = 1.60–33.44). HR‐HPV showed a sensitivity of 88.8% and a specificity of 80%. Ecto+/endocervical+ (16.7%), uncertain (19.4%) and ecto−/endocervical+ margins (9.1%) showed a higher risk of recurrence (odds ratio [OR] = 13.20, 95% CI = 1.02–170.96; OR = 15.84, 95% CI = 3.02–83.01; and OR = 6.60, 95% CI = 0.88–49.53, respectively). Women with involved margins and/or who were HR‐HPV positive had more treatment failure than those who were HR‐HPV negative or had clear margins (P‐log‐rank <0.001).ConclusionsHR‐HPV and margins seem essential for stratifying post‐LLETZ risk, and enable personalised management. Given that clear margins present a lower risk, a large excision may be indicated in older women to reduce the risk.Tweetable abstractAfter LLETZ for CIN 2–3, recurrences appear more often in women with positive HR‐HPV and involved margins and aged over 35.