Editorial
New Insights in Endometrial Cancer Treatment
Androutsopoulos G*, Michail G and Decavalas G
Department of Obstetrics and Gynecology, University of Patras, Medical School, Rion, Greece
*Corresponding author: Georgios Androutsopoulos, Department of Obstetrics and Gynecology, University of Patras, Medical School, Rion 26504, Greece
Published: 29 Jul, 2016
Cite this article as: Androutsopoulos G, Michail G,
Decavalas G. New Insights in
Endometrial Cancer Treatment. Clin
Oncol. 2016; 1: 1040.
Editorial
Nowadays, endometrial cancer (EC) represents the most common malignancy of the female
genital tract in developed countries [1-5]. The estimated average life time risk for EC in the United
States, is approximately 2.64%. EC most commonly occurs in postmenopausal women [1-5]. The
sporadic EC based on its clinical and pathological features is classified into 2 different types (type
I EC and type II EC) and the classification has a crucial role for the entire management of EC
patients [6,7]. It is interesting to note, that the international scientific societies (ACOG, FIGO,
SGO and ESMO) recommend the systematic surgical staging as the initial treatment approach
in patients with EC [3-5,8-12]. More specifically, the systematic surgical staging in patients with
type I EC (endometrioid) includes: total hysterectomy, bilateral salpingo-oophorectomy, pelvic
and para-aortic lymphadenectomy and complete resection of any suspicious lesion [2-5,8-15].
On the contrary, the systematic surgical staging in patients with type II EC (poorly differentiated,
papillary serous, clear cell) includes: total hysterectomy, bilateral salpingo-oophorectomy, pelvic
and para-aortic lymphadenectomy, total omentectomy, appendectomy and complete resection of
any suspicious lesion [3-5,10,11,14-16]. Additionally, pelvic washings are necessary for both types
of EC, although they do not affect FIGO staging [9]. The systematic surgical staging in patients with
EC can be performed either with laparotomy or laparoscopy [2-5,8,10-12,17-20]. When applied in
EC patients, both of them have similar results in recurrence rates and they associated with similar
overall and disease-free survival rates [10,12,17,18]. Nevertheless, minimally invasive techniques
have significant advantages especially in overweight and elderly patients (smaller incisions,
improved visualization, shorter hospital stay, less postoperative pain, quicker recovery and low risk
for postoperative complications) [3-5,8,10-12,17-21]. Laparotomy is the most preferable approach
for systematic surgical staging in patients with EC [3-5,10,11,17,18]. In sharp contrast, minimally
invasive techniques (laparoscopy and robotic-assisted surgery) are significantly more difficult and
time consuming and require special surgical skills [2-5,8,10-12,17-20]. This is the reason why,
minimally invasive techniques are less popular and we use them only in EC patients with early stage
disease [2-5,8,10-12,17-20]. It is also worth noting, that pelvic and para-aortic lymphadenectomy
has an essential role for systematic surgical staging in patients with EC [3-5,11,14,15] It is the only
way to diagnose EC patients at stage IIIc [3-5,8,9,11-13,22,23]. Furthermore, pelvic and paraaortic
lymphadenectomy improves survival in patients with advanced stage type I EC and in all
patients with type II EC [2-5,11,24-28]. In contrast, pelvic and para-aortic lymphadenectomy do
not improve survival in patients with early stage type I EC [2-5,11,12,29,30]. Nevertheless, the
extent of pelvic and para-aortic lymphadenectomy (>14 lymph nodes) in patients with EC, increases
significantly the risk for postoperative complications [3-5,11,29,31,32]. As a consequence, in elderly
patients and in patients with relative comorbidities (obesity, diabetes and coronary artery disease)
we should carefully weigh the increased intraoperative and postoperative morbidity with any
survival advantage [3-5,8,11,31,33,34]. On the other hand, according to the recommendations of
the international scientific societies (ACOG, SGO and ESMO), postoperative adjuvant treatment
(radiotherapy and/or chemotherapy) plays a very important role in EC patients with increased risk
for recurrence or at advanced stage disease [2-5,8,10,11,13,35,36]. To begin with, the postoperative
adjuvant radiotherapy in EC patients includes vaginal brachytherapy and external radiotherapy [3-
5,10,11,36]. Vaginal brachytherapy is the treatment of choice in intermediate risk EC patients (stage
IA grade 3 endometrioid type EC, stage IB grade 1-2 endometrioid type EC) [3-5,10,11,36-41]. The
application of vaginal brachytherapy is well tolerated and it is associated with less side effects and
better quality of life [10,36-40,42]. Moreover, vaginal brachytherapy minimizes the risk for local
recurrences, but it does not affect overall survival [36,37,40,42]. Especially in intermediate risk EC
patients, vaginal brachytherapy and external pelvic radiotherapy have an equal role for the local
control of disease [3-5,10,11,36-39].
Similarly, external pelvic radiotherapy is the adjuvant treatment of choice in high risk EC patients
(stage IB grade 3 endometrioid type EC, stage I non-endometrioid type EC) [3-5,10,11,38,39,42].
The application of external pelvic radiotherapy is not well tolerated
and it is associated with significant morbidity and reduction in
quality of life [3-5,11,37,43]. Although external pelvic radiotherapy
minimizes the risk for local recurrences, it does not affect overall
survival [8,36-38,40,43,44]. In contrast, whole abdomen radiotherapy
is an alternative treatment option in EC patients with advanced stage
disease [45]. However, whole abdomen radiotherapy should be used
only in patients with completely resected disease [45]. Furthermore,
it has tolerable toxicity and may improve overall survival [3-5,11,45].
On the other hand, postoperative adjuvant chemotherapy is the
adjuvant treatment of choice in EC patients with advanced stage
disease [2-5,10,11,13,36,46,47]. Nevertheless, adjuvant chemotherapy
is more effective than whole abdomen radiotherapy, in EC patients
with advanced stage disease [3-5,11,35-48]. The most common used
chemotherapeutic agents in EC patients, are: taxanes, anthracyclines
and platinum compounds [46,49]. The application of postoperative
adjuvant chemotherapy achieves high response rates, but it has
only modest effect in progression free survival and overall survival
[3-5,11,46]. Nowadays, the postoperative combination of adjuvant
radiotherapy with adjuvant chemotherapy shows promising
results, particularly in high risk EC patients and in EC patients at
advanced stage disease [3-5,11,36,46,50]. Especially in EC patients
with systematic surgical staging, the combined application of
adjuvant radiotherapy and adjuvant chemotherapy reduces the risk
of relapse or death and increases overall survival [3-5,10,11,36,51].
Additionally, the combined application of adjuvant radiotherapy and
adjuvant chemotherapy is more effective than the isolated application
of adjuvant radiotherapy [3-5,11,36,46,51].
Recent years, molecular targeted therapies are very popular in the
treatment of various types of cancer [3-5,11]. Those therapies, usually
target essential signaling pathways (EGFR, VEGFR and PI3K/PTEN/
AKT/mTOR).52-54 However, they have not studied well in EC and they
have only modest effect in unselected EC patients [3-5,11,46,55,57].
In this light, ErbB-targeted therapies can be used as an adjuvant
treatment in well-defined subgroups of EC patients (type II EC) with
EGFR and ErbB-2 over expression [3-5,11,14,15,54-68]. Moreover,
their efficacy in those subgroups of EC patients, should be further
evaluated with prospective clinical trials and adequate number of
patients [3-5,11,14,15,54-68]. In conclusion, the systematic surgical
staging plays an essential role in the treatment of EC patients and
offers many diagnostic, prognostic and therapeutic benefits [2-
5,8,11,14,15]. Moreover, it clearly affects the decision for the
appropriate postoperative adjuvant treatment in EC patients, in order
to maximize survival and minimize the morbidity of over-treatment
(radiation injury) and the effects of under-treatment (recurrent
disease, increased mortality) [2-5,8,11,14,15].
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