“Endometrial Cancer – What’s Changing? »

Posted on November 20, 2022

Endometrial cancer is the 6th most common in women and the 15th in general, being the most common gynecological cancer in developed countries. In 2020, more than 417,000 new cases were recorded worldwide.

Its incidence and mortality are increasing globally. Over the past decade, for example, in the UK, deaths have increased by 25%, a trend that has also been reported in other developed countries.

The endometrial cancer death rate is expected to increase by a further 19% in the UK between 2014 and 2035.

Although the aging of the population has contributed to this trend, the increase in the number of cases accompanies the increase in the incidence of various risk factors. Obesity seems to be the main risk factor, although there are others that are also important, such as hypertension, diabetes mellitus and polycystic ovary syndrome.

About 90% of endometrial carcinomas are manifested by abnormal uterine bleeding, allowing, in most cases, an early diagnosis. Early-stage endometrial carcinoma has an excellent prognosis, with a high cure rate. On the contrary, advanced disease is generally associated with a poor prognosis.

This is one of the reasons caregivers and women are aware of this early symptom which, if properly managed, saves lives, reduces suffering and saves resources.

The approach to this oncological gynecological pathology has evolved the most in recent years. One of the main changes occurred in the classification. Although the classical histological characterization was maintained, the molecular characterization was introduced, initially based on the data of the TCGA study and later confirmed by the application of a diagnostic algorithm based on the immunohistochemical study of p53 proteins. and the “mismatch repair” (MMR) and in the search for pathogenic mutations in the exonuclease domain of the POLE gene.

It is a tool that introduces important changes in the therapeutic approach with a prognostic impact.

Henrique Nabais

Another significant change has occurred in surgery. In recent years, the classic surgical approach (laparotomy or “open surgery”) has been replaced by minimally invasive surgery in cases of disease limited to the uterus, which is associated with less blood loss, longer duration shorter hospital stay, fewer intra and postoperative complications and better quality of life for patients.

Today, it is considered by medical societies, both national and international, that the use of this new approach is a quality criterion for centers that treat endometrial cancer, and surgery by laparotomy is not is not defensible in the vast majority of patients.

Minimally invasive surgery itself has also undergone a notable evolution, starting with conventional laparoscopy and then evolving into robot-assisted laparoscopy. Many international reference centers practice almost exclusively the robotic approach in the surgical treatment of endometrial cancer, with obvious advantages for patients and for health care in general. In Portugal, this path has already been followed.

Along the same lines, less surgical aggressiveness and overlap or greater oncological safety, is the use of sentinel node biopsy.

This is already routinely used in certain cancers such as breast, vulva and melanoma. This concept is based on the fact that, in cancer of a solid organ, lymph node dissemination occurs in a segmental and predictable manner, the sentinel lymph node being the first node in the tumor drainage lymphatic network.

It is assumed that if the sentinel lymph node does not have the disease, neither do the others. It aims to avoid unnecessary lymphadenectomies, to reduce the morbidity of the surgical procedure and, on the other hand, to increase the rate of detection of lymph node metastases, in particular those of small volume and atypical location.

Today, sentinel lymph node biopsy is recommended in centers where the technique is validated, in low and intermediate risk pre-surgical groups. For patients in the preoperative high-risk group, systematic bilateral pelvic and para-aortic lymphadenectomy down to the level of the left renal vein is recommended, with sentinel lymph node biopsy being an alternative in patients at high risk and/or with significant comorbidities.

Another relevant change is the increasingly frequent use of volume reduction surgery, with the aim of eliminating gross disease, in selected cases of advanced or recurrent disease.

Recent advances in understanding the molecular biology of this group of cancers have also enabled the development of new strategies in terms of targeted and personalized chemotherapy.

Examples are the use of levatinib (a VEGFR2 – vascular endothelial growth factor receptor 2 inhibitor) and immunotherapy with pembrolizumab in relapsing disease. The many clinical trials taking place today will allow, in the near future, a decisive advance in the medical approach to these cancers.

In the current context, the most important message is that of optimism, because, despite the increase in the incidence rate, we also have increasingly effective weapons in their fight.

Article published in women’s medicine September/December, a leading journal in the field of gynecology/obstetrics and women’s health in Portugal.
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