Introduction
Endometrial cancer (EC) is the second most common gynaecological cancer worldwide with 417,367 cases diagnosed globally in 2020(1). Global estimates showing rising incidence rates in both developed and developing countries (2). EC can be divided into 2 subtypes: type 1, the oestrogen-dependent endometrioid type associated with obesity that accounts for up to 85% of ECs, and type 2, the non-endometrioid subtypes that include serous, clear-cell, undifferentiated carcinomas and malignant mixed Mullerian tumours and are typically not associated with obesity (3, 4). Although the majority of patients with EC are diagnosed when they are postmenopausal, about 20% of patients are diagnosed when they are still of reproductive age. The majority of these patients tend to present with low-grade early stage tumours of the endometrioid subtype that are confined to the endometrium (5).
The standard treatment for early EC is total hysterectomy, bilateral salpingo-oopherectomy (THBSO) with or without lymphadenectomy(6, 7). Following current standard surgical treatment, the 5-year survival for EC is good, ranging from 74% to 91%, particularly for women diagnosed with low-grade endometrioid tumours without lymph node involvement (8). However, given the current trends of women of reproductive age delaying childbearing(9) and the rising incidence of EC amongst nulliparous women, an alternative treatment is necessary for patients who desire preservation of childbearing potential. Fertility sparing treatment for EC can be considered for a select group of patients who have FIGO grade 1 tumour of the endometrioid subtype, without myometrial invasion, lymph node involvement or distant metastasis. This treatment approach mainly involves endocrine therapy with oral progestins, gonadotropin-releasing hormone (GnRH) agonists or levonorgestrel-releasing intra-uterine devices. Patients on this treatment protocol require regular surveillance with endometrial biopsy until tumour regression(10). However, medical treatment alone for EC has the problems of long response time, unpredictable response and high recurrence rates.
Obesity is an established risk factor for EC, mainly due to the endogenous hyper-estrogenic state it creates in a patient’s body. The worldwide epidemic of obesity is likely to be a key factor in the increasing incidence of EC (11). Despite this clear link between obesity and EC, there is a paucity of data studying the effect of weight loss induced by bariatric surgery (BS) as part of the fertility sparing treatment. BS has been shown to be an effective treatment of obesity, producing sustained and significant weight loss, along with improvement in multiple obesity-related co-morbidities(12). At the tissue level, BS is associated with downregulation of pro-proliferative signalling pathways, reduced endometrial growth, and spontaneous clearance of both latent and precursor endometrial neoplastic lesions (13). BS is also associated with reducing the odds of developing EC in obese women(14). Based on these factors, there is a strong biological rationale that weight loss induced from BS is an important factor that could contribute to successful regression of EC in patients on fertility sparing treatment. Additional benefits of BS for this group of patients include improvement in overall health from weight loss and improvement in fertility rates (from both natural conception and assisted reproduction) after fertility sparing treatment. In the event that these patients require surgical resection for EC in the future, weight loss also reduces peri-operative risks and improves success rates for minimally invasive techniques.
The aim of this study is to provide a case series of patients on fertility sparing treatment who underwent BS for the treatment of morbid obesity. The primary outcome of the study is to report on the early regression of EC (within six months) with successful weight loss after BS. The secondary outcome of the study is to report outcomes from BS including weight loss and improvement in related medical co-morbidities. In addition, we aim to review the literature on the relationship between morbid obesity and EC, as well as the role of BS in the fertility sparing treatment of obese patients with early EC.