Endometrial cancer (EC) is the most common gynaecologic malignancy in developed countries. The main challenge in EC management is to correctly estimate the risk of metastases at diagnosis and the risk to develop recurrences in the future. Risk stratification determines the need for surgical staging and adjuvant treatment. Detection of occult, microscopic metastases upstages patients, provides important prognostic information and guides adjuvant treatment. The molecular classification subdivides EC into four prognostic subgroups: POLE ultramutated; mismatch repair deficient (MMRd); nonspecific molecular profile (NSMP); and TP53 mutated (p53abn). How surgical staging should be adjusted based on preoperative molecular profiling is currently unknown. Moreover, little is known whether and how other known prognostic biomarkers affect prognosis prediction independent of or in addition to these molecular subgroups. This review summarizes the factors incorporated in surgical staging (i.e., peritoneal washing, lymph node dissection, omentectomy and peritoneal biopsies), and its impact on prognosis and adjuvant treatment decisions in an era of molecular classification of EC. Moreover, the relation between FIGO stage and molecular classification is evaluated including the current gaps in knowledge and future perspectives.

Background: Interest is growing in the dynamic role of gut microbiome disturbances in human health and disease. No direct evidence is yet available to link gut microbiome dysbiosis to endometrial cancer. This review aims to understand any association between microbiome dysbiosis and important risk factors of endometrial cancer, high estrogen levels, postmenopause and obesity. Methods: A systematic search was performed with PubMed as primary database. Three separate searches were performed to identify all relevant studies. Results: Fifteen studies were identified as highly relevant and included in the review. Eight articles focused on the relationship with obesity and eight studies focused on the menopausal change or estrogen levels. Due to the heterogeneity in patient populations and outcome measures, no meta-analysis could be performed. Both the menopausal change and obesity were noted to enhance dysbiosis by reducing microbiome diversity and increasing the Firmicutes to Bacteroidetes ratio. Both also incurred estrobolome changes, leading to increased systemic estrogen levels, especially after menopause. Furthermore, microbiome dysbiosis was reported to be related to systemic inflammation through toll-like receptor signaling deficiencies and overexpression of pro-inflammatory cytokines. Conclusions: This review highlights that the female gut microbiome is intrinsically linked to estrogen levels, menopausal state and systemic inflammation, which indicates gut microbiome dysbiosis as a potential hallmark for risk stratification for endometrial cancer. Studies are needed to further define the role the gut microbiome plays in women at risk for endometrial cancer.

Background: Lymph node dissection (LND) is recommended as staging procedure in presumed low stage endometrial cancer. LND is associated with risk of lower-extremity lymphedema and post-operative complications. The sentinel lymph node (SLN) procedure has been shown to have high diagnostic accuracy, but its effects on complication risk has been little studied. This systematic review compares the risk of lower-extremity lymphedema and post-operative complications in SLN versus LND in patients with endometrial carcinoma. Methods: A systematic search was conducted in PubMed and Cochrane Library. Results: Seven retrospective and prospective studies (total n = 3046 patients) were included. Only three studies reported the odds ratio of lower-extremity lymphedema after SLN compared to LND, which was 0.05 (95% CI 0.01–0.37; p = 0.067), 0.07 (95% CI 0.00–1.21; p = 0.007) and 0.54 (95% CI 0.37–0.80; p = 0.002) in these studies. The pooled odds ratio of any post-operative complications after SLN versus LND was 0.52 (95% CI 0.36-0.73; I² = 48%; p < 0.001). For severe post-operative complications the pooled odds ratio was 0.52 (95% CI 0.28–0.96; I² = 0%; p = 0.04). Conclusions: There are strong indications that SLN results in a lower incidence of lower-extremity lymphedema and less often severe post-operative complications compared to LND. In spite of the paucity and heterogeneity of studies, direction of results was similar in all studies, supporting the aforementioned conclusion. These results support the increasing uptake of SLN procedures in endometrial cancer.

The number of women treated for gynecological cancer is increasing. At the same time, the duration of in-patient hospitalization has decreased, and follow-up with its primary focus on early recognition of recurrence does not meet all patients’ needs. One method of follow-up may be digital intervention. This study describes the development of a psychoeducational Internet-delivered intervention targeting women’s psychosocial needs during the follow-up period after treatment for gynecological cancer. The project consisted of three phases following the UK Medical Research Council Framework guidelines for the development of complex interventions. Phase one identified the evidence in the field, phase two identified the relevant theoretical framework, and phase three included a two-year work process including focus group interviews and think aloud interviews with users. Through the steps of literature review, theoretical framework, and an iterative development process with users and other stakeholders, a six-week program was developed. The program included psychoeducational information, multimedia, exercises, and weekly telephone follow-up with a dedicated nurse. This Internet-delivered intervention can be a novel method for addressing the gap in the provision of follow-up for women after treatment for gynecological cancer.

(1) Background: This study evaluated the clinical outcome after salvage radiotherapy for first pelvic relapse after endometrial cancer (EC). (2) Methods: This multicenter retrospective study included EC patients with first central pelvic relapse without lymph node involvement treated with curative intent. Progression-free (PFS) and overall survival (OS) were calculated with the Kaplan–Meier method and possible predictive factors for risk of relapse and mortality were identified using the Cox model. (3) Results: We included 139 patients with median EQD2 (Equivalent Dose in 2 Gy fractions) to the clinical target volume of 70.0 Gy. During follow up of median 6.66 years, 39.6% patients developed a second relapse. Risk group classification at primary diagnosis based on histology, grading and FIGO stage and how the pelvic tumor boost was administered were independently associated with PFS and OS. Five-year OS was 68% (95% CI (59–75)) for the whole cohort. Five-year OS was 88% (95% CI (75–94)), 72% (95% CI (55–84)) and 38% (95% CI (15–60)) for the stage I low-, intermediate- and high-risk group, respectively. (4) Conclusions: The majority of central pelvic recurrences in RT-naive EC women can be successfully salvaged with radiotherapy. However, survival in patients with high-risk disease remains poor and warrants a more individualized approach to optimize outcome.

Background: Response to hormonal therapy in advanced and recurrent endometrial cancer (EC) can be predicted by oestrogen and progesterone receptor immunohistochemical (ER/PR-IHC) expression, with response rates of 60% in PR-IHC > 50% cases. ER/PR-IHC can vary by tumour location and is frequently lost with tumour progression. Therefore, we explored the relationship between ER/PR-IHC expression and tumour location in EC. Methods: Pre-treatment tumour biopsies from 6 different sites of 80 cases treated with hormonal therapy were analysed for ER/PR-IHC expression and classified into categories 0–10%, 10–50%, and >50%. The ER pathway activity score (ERPAS) was determined based on mRNA levels of ER-related target genes, reflecting the actual activity of the ER receptor. Results: There was a trend towards lower PR-IHC (33% had PR > 50%) and ERPAS (27% had ERPAS > 15) in lymphogenic metastases compared to other locations (p = 0.074). Hematogenous and intra-abdominal metastases appeared to have high ER/PR-IHC and ERPAS (85% and 89% ER-IHC > 50%; 64% and 78% PR-IHC > 50%; 60% and 71% ERPAS > 15, not significant). Tumour grade and previous radiotherapy did not affect ER/PR-IHC or ERPAS. Conclusions: A trend towards lower PR-IHC and ERPAS was observed in lymphogenic sites. Verification in larger cohorts is needed to confirm these findings, which may have implications for the use of hormonal therapy in the future.