Fertility-Sparing Approach in Patients with Endometrioid Endometrial Cancer Grade 2 Stage IA (FIGO): A Qualitative Systematic Review

Abstract

Background. Endometrial cancer (EC) is one of the most common gynecologic malignancy, mostly in postmenopausal women. The gold standard treatment for EC is surgery, but in the early stages, it is possible to opt for conservative treatment. In the last decade, different clinical and pathological markers have been studied to identify women who respond to conservative treatment. A lot of immunohistochemical markers have been evaluated to predict response to progestin treatment, even if their usefulness is still unclear; the prognosis of this neoplasm depends on tumor stage, and a specific therapeutic protocol is set according to the stage of the disease. Objective. (1) To provide an overview of the conservative management of Stage 1A Grade (G) 2 endometrioid EC (FIGO) and the oncological and reproductive outcomes related; (2) to describe the molecular alterations before and after progestin therapy in patients undergoing conservative treatment. Materials and Methods. A systematic computerized search of the literature was performed in the main electronic databases (MEDLINE, Embase, Web of Science, PubMed, and Cochrane Library), from 2010 to September 2021, in order to evaluate the oncological and reproductive outcomes in patients with G2 stage IA EC who ask for fertility-sparing treatment. The expression of several immunohistochemical markers was evaluated in pretreatment phase and during the follow-up in relation to response to hormonal therapy. Only scientific publications in English were included. The risk of bias assessment was performed. Review authors’ judgments were categorized as “low risk,” “high risk,” or “unclear risk” of bias. Results. Twelve articles were included in the study: 7 observational studies and 5 case series/reports. Eighty-four patients who took progestins (megestrol acetate, medroxyprogesterone acetate, and/or levonorgestrel-releasing intrauterine devices) were analyzed. The publication bias analysis turned out to be “low.” 54/84 patients had a complete response, 23/84 patients underwent radical surgery, and 20/84 had a relapse after conservative treatment. Twenty-two patients had a pregnancy. The length of follow-up was variable, from 6 to 142 months according to the different studies analyzed. Several clinical and pathological markers have been studied to identify women who do not respond to conservative treatment: PR and ER were the most studied predictive markers, in particular PR appeared as the most promising; MMR, SPAG9, Ki67, and Nrf2-survivin pathway provided good results with a significant association with a good response to progestin therapy. However, no reliable predictive markers are currently available to be used in clinical practice. Conclusions. The conservative treatment may be an option for patients with stage IA G2 EEC who desire to preserve their fertility. The immunohistochemical markers evaluation looks promising in predicting response to conservative treatment. Further large series and randomized clinical trials are needed to confirm these results.

Validation of a deep neural network-based algorithm supporting clinical management of adnexal mass

“…Information on imaging and physician impression of the masses was also not recorded frequently 10.3389/fmed.2023.1102437 enough to allow meaningful stratification on other diagnostic factors and this may hide interesting interactions in the data. Even though the study did not collect specific information of benign masses, the performance of OvaWatch might support the evaluation of adnexal mass suspicious as endometriosis cysts versus a mass arising from an endometrioid ovarian cancer or metastatic endometrial cancer to the ovary (32,(35)(36)(37)(38)(39) through the testing result of low probability of malignancy versus indeterminate.…”

Fertility Preservation in Endometrial Cancer—Treatment and Molecular Aspects

“…Progesterone receptors are more likely present in these well-differentiated tumor cells which leads to a response to progestin therapy [ 2 ]. However, there are no predictive markers of progestogen resistance available at the current time [ 45 ]. The following options are available: LNG-IUS (52 mg) with or without gonadotropin-releasing hormone receptor agonists (GnRH-agonists), oral progesterone such as medroxyprogesterone acetate (400–600 mg/day), or megestrol acetate (160–320 mg/day).…”

“…The selection of patients suitable for fertility should be chosen carefully by a comprehensive pretreatment evaluation. Basic requirements for fertility preservation treatment are the absence of a contraindication to medical therapy or pregnancy per se [ 45 ]. Patients with a poorer outcome, itself due to secondary diseases such as other cancers like breast cancer, stroke, deep vein thrombosis, pulmonary embolism or myocardial infarction, a resulting relative or absolute contraindication to hormone therapy as well as a resulting lower successful birth probability, should be advised very critically with regard to fertility preservation [ 18 , 45 ].…”

Role of Machine Learning (ML)-Based Classification Using Conventional 18F-FDG PET Parameters in Predicting Postsurgical Features of Endometrial Cancer Aggressiveness

“…Radical surgery and lymphadenectomy are generally recommended for high risk patients. However, the correct selection of patients who might benefit from this kind of treatment is still challenging [7] and, especially when dealing with young patients of reproductive age, fertility sparing approaches need to be considered [8][9][10]. International Federation of Obstetrics and Gynecology (FIGO) stage, histology, depth of myometrial invasion (MI) [7], and lymph node (LN) metastases are the most commonly reported features of EC aggressiveness [11][12][13].…”