Complete pathological response following levonorgestrel intrauterine device in clinically stage 1 endometrial adenocarcinoma: Results of a randomized clinical trial.

PURPOSE: Intrauterine levonorgestrel (LNG-IUD) is used to treat patients with endometrial adenocarcinoma (EAC) and endometrial hyperplasia with atypia (EHA) but limited evidence is available on its effectiveness. The study determined the extent to which LNG-IUD with or without metformin (M) or weight loss (WL) achieves a pathological complete response (pCR) in patients with EAC or EHA. PATIENTS AND METHODS: This phase II randomized controlled clinical trial enrolled patients with histologically confirmed, clinically stage 1 FIGO grade 1 EAC or EHA; a body mass index > 30 kg/m2; a depth of myometrial invasion of less than 50% on MRI; a serum CA125 ≤ 30 U/mL. All patients received LNG-IUD and were randomized to observation (OBS), M (500 mg orally twice daily), or WL (pooled analysis). The primary outcome measure was the proportion of patients developing a pCR (defined as absence of any evidence of EAC or EHA) after 6 months. RESULTS: From December 2012 to October 2019, 165 patients were enrolled and 154 completed the 6-months follow up. Women had a mean age of 53 years, and a mean BMI of 48 kg/m2. Ninety-six patients were diagnosed with EAC (58%) and 69 patients with EHA (42%). Thirty-five participants were randomized to OBS, 36 to WL and 47 to M (10 patients were withdrawn). After 6 months the rate of pCR was 61% (95% CI 42% to 77%) for OBS, 67% (95% CI 48% to 82%) for WL and 57% (95% CI 41% to 72%) for M. Across the three treatment groups, the pCR was 82% and 43% for EHA and EAC, respectively. CONCLUSION: Complete response rates at 6 months were encouraging for patients with EAC and EHA across the three groups. TRIAL REGISTRATION: U.S. National Library of Medicine, NCT01686126.

Patient experiences of conservative treatment for early stage endometrial cancer and endometrial hyperplasia with atypia using levonorgestrel intrauterine device: A qualitative study.

OBJECTIVE: The aim of the study was to obtain an in-depth understanding of the experience of women who received non-surgical treatment for endometrial adenocarcinoma (EAC) or endometrial hyperplasia with atypia (EHA). Enhanced understanding of women's experiences of non-surgical treatment is essential to inform counselling of the growing number of patients in this field. METHODS: Individual semi-structured interviews were conducted with 21 women who received conservative (non-surgical hormonal) treatment for early stage EAC or EHA using the levonorgestrel intrauterine device (LNG-IUD) as part of the feMMe trial (NCT01686126). All interviews were audiotaped and transcribed verbatim prior to content analysis. RESULTS: Of the 21 women interviewed, ten received conservative treatment for early stage EAC and 11 received conservative treatment for EHA. Five overarching themes were identified: i) extensive information and support needs (e.g. understanding of how the LNG-IUD treatment worked); ii) gratitude for treatment choice and non-surgical options (e.g. avoidance of potential risks associated with surgery); iii) onco-fertility (e.g. desire to maintain reproductive potential); iv) patient experience of overweight and obesity related to EAC development (e.g. history of trauma and disordered eating, multiple unsuccessful weight loss attempts); and v) patient experience of treatment options and actual non-surgical treatment (e.g. desire for early referral to counselling services). CONCLUSIONS: This qualitative investigation enabled novel insights into the treatment preferences and decision-making process of women with newly diagnosed EHA and EAC when offered non-surgical treatment options. These insights facilitate the development of pragmatic guidance and decision support tools that could be tested in future clinical trials.

Improving treatment for obese women with early stage cancer of the uterus: rationale and design of the levonorgestrel intrauterine device ± metformin ± weight loss in endometrial cancer (feMME) trial.

PURPOSE: Endometrial adenocarcinoma (EC) is the most common gynaecologic cancer. Up to 90% of EC patients are obese which poses a health threat to patients post-treatment. Standard treatment for EC includes hysterectomy, although this has significant side effects for obese women at high risk of surgical complications and for women of childbearing age. This trial investigates the effectiveness of non-surgical or conservative treatment options for obese women with early stage EC. The primary aim is to determine the efficacy of: levonorgestrel intrauterine device (LNG-IUD); with or without metformin (an antidiabetic drug); and with or without a weight loss intervention to achieve a pathological complete response (pCR) in EC at six months from study treatment initiation. The secondary aim is to enhance understanding of the molecular processes and to predict a treatment response by investigating EC biomarkers. METHODS: An open label, three-armed, randomised, phase-II, multi-centre trial of LNG-IUD ± metformin ± weight loss intervention. 165 participants from 28 centres are randomly assigned in a 3:3:5 ratio to the treatment arms. Clinical, quality of life and health behavioural data will be collected at baseline, six weeks, three and six months. EC biomarkers will be assessed at baseline, three and six months. CONCLUSIONS: There is limited prospective evidence for conservative treatment for EC. Trial results could benefit patients and reduce health system costs through a reduction in hospitalisations and through lower incidence of adverse events currently observed with standard treatment.