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.