20 to 30 . The incidence of endometrial cancer in some developed cities has reached the level of gynecological malignancy

The incidence of endometrial cancer has reached the first place in gynecological malignant tumors in some developed cities.

The treatment of endometrial cancer should be a comprehensive treatment based on surgical treatment. In order to improve the diagnosis and treatment of endometrial cancer, standardize the diagnostic basis, diagnosis and differential diagnosis, treatment principles and treatment plans, we now propose guidelines for the diagnosis and treatment of endometrial cancer. This guideline is based on the internationally recognized guidelines for the treatment of cervical cancer [such as the National Comprehensive Cancer Network (NCCN) guidelines, the International Federation of Gynecology and Obstetrics (FIGO) guidelines, and the International Association of Gynecology and Obstetrics (IAGO) guidelines. The guidelines of the National Comprehensive Cancer Network (NCCN), the International Federation of Gynecology and Obstetrics (FIGO), and so on, are combined with those of China.

Revised from previous guidelines. This guideline applies to endometrioid adenocarcinoma, specific types of endometrial cancer (clear cell carcinoma, plasmacytoma), and uterine carcinosarcoma. In clinical practice, endometrial cancer emphasizes planned, rational and comprehensive treatment, and individualized treatment. Clinicians need to take into account the hospital’s facilities, technical conditions and the patient’s condition to standardize treatment. For clinical cases not covered by this guideline, it is recommended that the physician in charge give reasonable individualized treatment according to the patient’s condition and encourage participation in clinical trials.

II. Diagnostic Techniques and Applications

(I) Monitoring and screening of risk factor populations.

Endometrial cancer is classified into estrogen-dependent (type I) and non-estrogen-dependent (type II) according to the pathogenesis and biological behavior. Most of the pathological types of estrogen-dependent endometrial cancer are endometrioid adenocarcinoma, and a few are mucinous adenocarcinoma; the pathological types of non-estrogen-dependent endometrial cancer include plasmacytoma, clear cell carcinoma, and carcinosarcoma.

Most endometrial cancers belong to type I. The development of type I endometrial cancer is directly related to the continuous stimulation of estrogen without progesterone antagonism, and the lack of progesterone counteracts the prolonged hyperplasia of the endometrium, which further develops into endometrial cancer. The mechanism of type II endometrial carcinogenesis is still not fully understood.

The main risk factors are as follows.

• Reproductive endocrine disorders: such as anovulatory menstrual abnormalities, anovulatory infertility, and polycystic ovary syndrome. The lack of progesterone antagonism in the endometrium due to the absence of cyclic ovulation and the prolonged action of a single estrogen cause the endometrium to hyperplasia and even cancer.
  

• < span style="font-size:16pt">Obesity, hypertension, and diabetes, also known as the endometrial cancer triad: studies have shown that every 1 unit increase in body mass index (kg/m22 size:16pt”>), the relative risk of endometrial cancer increased by 9%. Compared with women with a body mass index <25, women with a body mass index between 30 and 35 had an approximately 1.6-fold increased risk of endometrial cancer, and women with a body mass index >35 had a 3.7-fold increased risk of endometrial cancer.
  

  fold. 2.8-fold increased risk in diabetics or those with abnormal glucose tolerance compared to normal

  1.8-fold increase in those with hypertension.

• Early menarche versus late menopause: Women with late menopause have mostly anovulatory periods in the later years, thus prolonging the duration of estrogen stimulation without progesterone synergy. This prolongs the duration of estrogen stimulation without progesterone synergy. 4. Infertility: infertility increases the risk of endometrial cancer, and with
  

  contrary to this, each pregnancy reduces the risk of endometrial cancer to some extent. In addition, the higher the age at last pregnancy, the lower the probability of developing endometrial cancer.

• Ovarian tumors: Some ovarian tumors, such as ovarian granulosa cell tumors and follicular membranous cell tumors, often produce high levels of estrogen, causing menstrual irregularities and menopause. This can cause menstrual irregularities, postmenopausal bleeding, endometrial hyperplasia and even endometrial cancer. Endometrial biopsy should be routinely performed in patients with these conditions.
  
• Exogenous estrogen: Single exogenous estrogen therapy for more than 5 years increases the risk of endometrial cancer by 10 to 30 times. Combined estrogen-progestin replacement therapy does not increase the risk of endometrial cancer.
  
• Genetic factors: Most patients with endometrial cancer are sporadic, with about 20 endometrial cancer patients have a family history. Patients with Lynch syndrome have an increased risk of developing malignancies outside the colon, including mainly endometrial, ovarian, and gastric cancers. Women with Lynch syndrome have a lifetime risk of developing endometrial cancer of up to 60.
  

An annual endometrial biopsy is recommended to evaluate for cancer. Prophylactic total hysterectomy/bilateral salpingo-oophorectomy may be recommended after delivery or even earlier. Hereditary endometrial cancer develops at a younger age than the average age of patients with sporadic endometrial cancer, so screening should be performed before age 50 years, and genetic testing and genetic counseling are recommended. Women with a family history of endometrial cancer have a correspondingly increased risk of endometrial cancer in other family members, and women with a first-degree relative with endometrial cancer have approximately 1.5 times the risk of endometrial cancer in the control group. 8. Other: Tamoxifen is a selective estrogen receptor modifier, both

It may exhibit estrogen-like effects or anti-estrogenic effects, depending on the target organ. Tamoxifen is an endocrine therapy for breast cancer, and studies have shown that long-term use can lead to endometrial hyperplasia and an increased risk of endometrial cancer.

9. Lifestyle: Some lifestyle factors are known to be associated with endometrial cancer, including dietary habits, exercise, alcohol consumption, and smoking.

To reduce the incidence of endometrial cancer, education should be provided to those with risk factors, including regulating lifestyle habits and hormone replacement therapy under the guidance of a physician. For those who have the above risk factors for endometrial cancer, insist on regular checkups for patients with hereditary family history and breast cancer patients who have been taking oral tamoxifen for a long time. However, so far, there is no recommended routine screening method for endometrial cancer. Ultrasound is an optional screening method. The main screening modality is transvaginal or transabdominal ultrasound to monitor endometrial thickness and abnormalities. There are no specific serum markers for hematology, so there is no routine monitoring of screening indicators.

(ii) Clinical presentation.

1. Age of onset

70

70 to 75 of patients are postmenopausal women with an average age of about 55 years. 2. Symptoms

• Vaginal bleeding: A small number of early endometrial cancers may be asymptomatic and clinically difficult to detect. However, the main symptom of 90endometrial cancer is various vaginal bleeding.
  
• Postmenopausal vaginal bleeding: Postmenopausal vaginal bleeding is the main symptom of patients with endometrial cancer, 90 More than 90 percent of postmenopausal patients present with vaginal bleeding symptoms. Vaginal bleeding can appear early in the course of the tumor; therefore, early-stage patients account for approximately 70 percent of first-time endometrial cancer patients.
  
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  • Menstrual disorders: about 20 of patients with endometrial cancer are perimenopausal women.
    

  Younger women under 40 years of age account for only 5 to 10 . Patients may present with disrupted menstrual cycles, dripping menstruation or even heavy vaginal bleeding.

• Abnormal vaginal discharge: early stage may be a small amount of plasma or bloody discharge. In the late stage, local infection and necrosis occur due to the increase of tumor size, and the discharge of foul-smelling pus and blood-like fluid.
  
• Pain: mostly vague pain in the lower abdomen, which can be caused by pus or fluid accumulation in the uterine cavity.
  
• Other: In the advanced stage, patients may palpate an enlarged uterus in the lower abdomen, which may appear present anemia, wasting, fever, cachexia, and other signs of systemic failure.
  

  3. Physical signs

  In the early stage of endometrial cancer, most patients have no obvious associated positive signs.

As most patients have combined diabetes, hypertension, or cardiovascular disease, attention should be paid to the associated systemic signs. On general examination, attention should be paid to the presence of anemia due to long-term blood loss. The lymph nodes in the supraclavicular, cervical, and inguinal areas should be palpated for enlargement.

The gynecologic triage should be performed during the specialist examination. The pelvic examination is mostly normal in early stage patients, and in some patients the uterus may be slightly soft in texture. In patients with advanced lesions involving the cervix, parametrial ligaments, adnexa, or significantly enlarged lymph nodes, the triple examination may reveal a hard or enlarged cervix or cervical canal, thickening and decreased elasticity of the main uterine ligament or uterosacral ligament, adnexal masses, and enlarged and fixed lymph nodes in the pelvic wall.

(iii) Adjunctive examinations.

Adjunctive diagnostic techniques for endometrial cancer include transabdominal or transvaginal ultrasound, magnetic resonance imaging (MRI), computerized tomography (CT), and positron emission tomography (PET). tomography (CT), positron emission tomography (PET)

(positron emission tomography (PET), etc.). Serum tumor markers can also be helpful in identifying benign and malignant lesions. However, the final diagnosis depends on pathology.

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• Blood biochemistry
  

Endometrial cancer can present with decreased hematocrit. Because most patients have combined diabetes, hypertension or cardiovascular disease, results in blood glucose and lipids need to be emphasized. Liver function and kidney function tests should also be performed.

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• Tumor marker test
  

There are no specific sensitive markers for endometrial cancer. Some patients may present with abnormal CA125 or CA19-9, CA153 or HE4, which are associated with histological type, myometrium

Depth of infiltration and extrauterine invasion are correlated and have some reference value for disease diagnosis and postoperative disease monitoring.

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• Imaging
  

• Ultrasound: There is a strong emphasis on ultrasound for the initial examination of patients with postmenopausal bleeding. Transvaginal ultrasonography is the most commonly used non-invasive method to determine the size of the uterus, the presence or absence of abnormalities in the uterine cavity, the thickness of the endometrium, the infiltration of the muscular layer, and the size and nature of adnexal masses. Endometrial thickness in postmenopausal women
  

  <5 mm, the negative predictive value can reach 96. If endometrial thickness>5mm, endometrial biopsy should be performed in postmenopausal patients. .

  In terms of ultrasound intervention, ultrasound-guided aspiration, drug injection, or tube drainage is indicated for encapsulated abdominal/pelvic fluid, paravalvular lymphatic cysts that do not resorb over time or are co-infected and cause significant discomfort. Intraoperative ultrasound can assist in determining the location of the lesion and avoiding important vascular organs. For those with suspected abdominal/pelvic organ, omental, or lymph node metastases during follow-up, ultrasound-guided mass aspiration biopsy is feasible.

  Elderly or severely ill patients require cardiac ultrasound for cardiac function, vascular ultrasound for possible complications such as deep vein thrombosis, and ultrasonography to help differentiate tumor emboli from thrombi.

• Pelvic MRI: The imaging method of choice for endometrial cancer, MRI can clearly visualize the endometrial and myometrial structures and is used to determine the size and location of the lesion, the depth of myometrial invasion, whether the cervix/vagina is invaded, and whether the vagina is invaded. Whether it invades the uterine body, vagina, bladder and rectum, as well as tumor dissemination in the pelvis and observation of lymph node metastasis in the pelvis, retroperitoneal area and inguinal area. It helps the tumor
  

Differential diagnosis (e.g., endometrial polyps, submucosal leiomyosarcoma, sarcoma, etc.). Evaluate the efficacy of chemotherapy and post-treatment follow-up.

• CT: CT is still of limited value in the diagnosis of early lesions. CT has the advantage of showing intermediate and advanced lesions, evaluating the invasion of the uterus, bladder and rectum, and showing abdominal/pelvic, retroperitoneal and bilateral inguinal lymph node metastases, as well as metastases to other organs in the abdominal and pelvic cavity and peritoneum. CT scan should be selected for patients with contraindications to MRI. Chest radiographs are routinely performed for endometrial cancer, but chest CT should be performed if necessary to exclude pulmonary metastases.
  
• PET: Rarely used in patients with initial diagnosis of endometrial cancer. PET is not recommended routinely for endometrial cancer in patients with clinical comorbidities that preclude surgical treatment, in patients with suspected metastases to uncommon sites, such as the skeleton or central nervous system, and in patients with biopsies suggesting high-grade tumors, including hypofractionated endometrial cancer, papillary plasmacytoma, clear cell carcinoma, and carcinosarcoma. PET is not routinely recommended for follow-up after treatment of endometrial cancer and should be considered only when recurrent metastases are suspected.
  
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  • Endometrial biopsy
    

  Histopathological examination of the endometrium is the final basis for diagnosis. The main methods to obtain the endometrium are diagnostic curettage and hysteroscopic biopsy.

  Diagnostic curettage should be performed to obtain tissue from the cervical canal and uterine cavity separately, i.e., segmental scraping. In order to understand the uterine cavity and the cervical canal.

  Direct hysteroscopic biopsy allows direct visualization of the morphology, location, and extent of lesions in the uterus and cervical canal and localizes biopsy or excision of suspicious lesions under direct visualization to reduce the rate of missed diagnoses. It is suitable for those with limited lesions. There is no prospective

Randomized studies have confirmed that hysteroscopy or surgery causes tumor dissemination, and there are no studies demonstrating that patients with endometrial cancer who undergo hysteroscopy have a better prognosis than those who undergo other tests. The prognosis of patients with endometrial cancer who undergo hysteroscopy is worse than that of patients with other endometrial cancers. It is important to emphasize that hysteroscopy should be performed with minimal dilation pressure and for as short a time as possible. However, the current tumescent pressure to avoid endometrial cell dissemination still needs to be clarified by clinical studies.

Indications for endometrial biopsy include postmenopausal or premenopausal irregular vaginal bleeding or bloody discharge, excluding cervical lesions; patients with anovulatory infertility for many years; persistent vaginal drainage; and imaging findings of abnormal endometrial thickening or The patient should have a high level of estrogen. Endometrial biopsy should also be performed in patients with some ovarian tumors that produce high levels of estrogen, such as granulosa cell tumors.

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• Cytological examination
  

Endometrial cells are not easily shed outside the menstrual period, and cancer cells shed from the uterine cavity are prone to lysis and denaturation and are not easily identified after staining; therefore, the positive rate of vaginal exfoliative cytology is not high. The other method is to obtain endometrial exfoliated cells via the uterine cavity, and the endometrial cell collector combined with liquid-based cytology filming technique is commonly used and has a higher accuracy.

(iv) Diagnostic criteria for endometrial cancer.

Pathologic diagnostic criteria: Histopathologic examination of the endometrium and biopsy of extrauterine metastases or surgical excision of tissue specimens, diagnosed as endometrial cancer by pathologic histology, is the gold standard.

(E) Differential diagnosis.

• Abnormal uterine bleeding: characterized by prolonged periods, increased menstrual flow, or irregular vaginal bleeding, similar to endometrial cancer symptoms. For these patients, especially
  

The endometrium should be obtained for pathologic examination to rule out endometrial cancer, even if there are no positive findings on gynecologic examination, in perimenopausal patients and young patients with combined infertility, scanty menstruation, or polycystic ovary syndrome. The endometrium should be obtained for pathological examination to exclude endometrial carcinoma even if gynecological examination is not positive.

• Age-related vaginitis: Common in postmenopausal women, presenting as bloody leukorrhea. The vaginal mucosa is atrophic and thin, congested, and bleeding spots are visible on examination. In these patients, ultrasound and cervical cytology are needed to rule out endometrial thickening, endometrial redundancy, and cervical lesions.
  
• Endometrial polyps or submucosal fibroids: manifest as excessive or prolonged menstruation, or bleeding with vaginal It is similar to endometrial cancer. The hysteroscopic examination and removal of the superfluous organisms can clarify the pathological diagnosis.
  
• Cervical cancer, uterine sarcoma and fallopian tube cancer: These diseases may also present with irregular vaginal bleeding and fluid discharge. In cervical cancer, the cervical canal can be thickened and hardened in a barrel shape by triage. If preoperative identification is not possible, HPV DNA testing is indicated and a positive result is indicative of cervical cancer. Uterine sarcoma is associated with short-term enlargement and tenderness of the uterus, and ultrasound and MRI show that most of the masses are located in the myometrium, which can help in the initial diagnosis. The main symptoms of tubal cancer are paroxysmal vaginal discharge, vaginal bleeding, and abdominal pain, and a mass in the adnexal region can be palpated on examination.
  

  (vi) Pathologic diagnosis.

  Pathologic diagnosis is the gold standard for the diagnosis of endometrial cancer. In most cases, especially in low-grade tumors, the diagnosis of endometrial cancer is highly reproducible, but

There is considerable interobserver diagnostic variability in the delineation of a subset of high-grade cancer subclasses, thus creating confusion in clinical management. The Cancer Genome Atlas (TCGA) of the National Cancer Institute studied 373 cases of endometrial cancer and combined genomic characterization to propose four molecular subtypes in endometrial cancer: the first group (POLE mutant) has the POLE mutation, and patients with POLE mutated tumors are associated with younger age (<60 years). The tendency is to consider them to have a good prognosis, but the results are currently inconsistent in international reports; group 2 micro

Satellite instability (MSI) type and group 3 microsatellite instability (MSI) type.

Group 1 low-copy number type, with a prognosis between Group 1 and Group 4. Group 4 high copy number phenotypes with high copy number variation and TP53 mutations were associated with poor prognosis. Notably, low-grade endometrioid carcinomas, the most common type of endometrial cancer, can exhibit four different genotypes, suggesting that genomic profiles can vary considerably in tumors with the same histologic pattern. In clinical work, TCGA methods can be introduced into clinical practice by using alternative methods of immunohistochemistry (P53, MSH2/6, PMS2/MLH1) and POLE mutation analysis. Particularly for assessing the prognosis of patients with high-grade endometrioid carcinoma, integrated stratification of microscopic and molecular features is the best approach for prognostic prediction of patients.

The pathological types of endometrial precancerous lesions and carcinomas according to the classification of female genital tumors in the 2020 edition include.

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• Precancerous lesions
  

The endometrial hyperplasia is divided into two categories, namely hyperplasia with and without atypia.

Endometrial hyperplasia without atypia is defined as glandular and endometrial interstitial

The ratio is disproportionate, with an increase in endometrial glands that are irregularly shaped, tubular, branched, and/or cystically dilated, similar to hyperplastic endometrium; however, there is no cytologic atypia. There are approximately 1 to 3 of uncomplicated atypical endometrial hyperplasia can progress to well-differentiated endometrioid adenocarcinoma.

Atypical endometrial hyperplasia/endometrial intraepithelial neoplasia

(endometrioid atypical hyperplasia , EAH / endometrioid intraepithelial neoplasia, EIN) is EAH / endometrioid intraepithelial neoplasia (EIN) is a cytologically atypical condition based on a disproportionate ratio of glands to endometrial mesenchyme in which the glandular epithelium is distinctly different from the surrounding non-neoplastic glands of the endometrium. It also contains many of the genetic changes commonly seen in endometrial carcinoma, including microsatellite instability, PAX2 inactivation, and PTEN, KRAS, and CTNNB1 mutations. When diagnosis is difficult, deletion of immune expression of PTEN, PAX2, or mismatch repair proteins can help in identification. Approximately one quarter to one third of patients with EAH/EIN in biopsy specimens are diagnosed with endometrioid carcinoma at subsequent hysterectomy or during the first year of follow-up. The long-term risk factor assessment showed a 14-fold probability of carcinoma in EAH compared with about 45-fold in EIN.

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• Endometrial carcinoma
  

At the time of pathologic diagnosis, the following 5 major pathologic types are included.

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• Endometrioid carcinoma.
  

The most common histologic type of endometrial carcinoma, accounting for approximately

60 to about 80 . Endometrioid carcinoma usually presents with glandular or chorionic glandular tubular structures with smooth official cavities and with crowded complex branching structures. The nuclear atypia is often mild to moderate, with inconspicuous nucleoli, and the cancer cells of high-grade endometrioid carcinoma are fine

The nucleus may be accompanied by marked atypia. The nuclear division index is highly variable. Interstitial infiltration is the key to distinguishing highly differentiated endometrioid carcinoma from EAH/EIN, as evidenced by the lack of segregated mesenchyme (glandular fusion or sieve-like structures), endometrial interstitial changes (pro-connective tissue reaction), or papillary structures (villous glandular structures).

Endometrioid carcinoma with squamous differentiation:10 ~25 of endometrioid carcinomas may see focal squamous differentiation. Foci of squamous differentiation may be located at the interstitial junction or may be mulberry-shaped, bridging adjacent glands. The recognition of squamous differentiation is important and must be distinguished from the solid growth areas described in the grading of endometrioid carcinoma.

Endometrioid carcinoma with secretory changes: The typical endometrioid carcinoma with secretory changes is almost always a highly differentiated carcinoma. This is occasionally seen in young fertile women, or those on progestin therapy, but most are postmenopausal and not on progestin therapy.

Endometrioid carcinoma with mucinous changes: Endometrial carcinoma with mucinous changes has the same molecular changes and prognosis as endometrial carcinoma, and is thus classified as a subtype of endometrioid carcinoma rather than as a separate mucinous carcinoma.

Histologic grading of endometrioid carcinoma is based on the extent of solidity in the tumor, with the following grading criteria: grade 1, solid growth area ≤5; grade 2, solid growth area of 6~50 ; grade 3, solid growth areas >50 . Areas exhibiting grade 3 nuclei exceeding 50 of the tumor are more aggressive and should be upgraded by 1 grade in the grading. If the nuclear anisotropy is disproportionate to the structure, then plasmacytoma should be excluded. The FIGO has now proposed a bifurcated grading scheme for endometrioid adenocarcinoma, with grade 1 and

Grade 2 endometrial carcinoma is classified as low grade, whereas grade 3 tumors are classified as high grade.

An uncommon pattern in grade 1 endometrioid carcinoma is microcystic, elongated, and

fragmentary infiltration, a pattern associated with lymphovascular invasion and lymph node metastasis without clear correlation with prognosis.

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• Plasmacytoid carcinoma
  

Plasmacytoid carcinoma may present as a complex papillary and/or glandular structure with diffuse and prominent nuclear pleomorphism. Most plasmacytomas have TP53 mutations, so p53 is abnormally expressed (at least 75tumor cells are diffusely strongly positive, or not expressed at all), helps to differentiate it from high-grade endometrioid carcinoma, which often shows a wild-type TP53 expression pattern, exhibiting less than 75Tumor cells express p53 positively to varying degrees, but a minority of high-grade endometrioid carcinomas may also have TP53 mutations. very high Ki-67 indices tend to be plasmacytotic, but like TP53 mutations, high-grade endometrioid carcinomas cannot be completely excluded. A subset of endometrioid carcinomas can be associated with plasmacytoma, called mixed plasmacytoma-endometrioid, and their prognosis depends on the plasmacytoma component of the carcinoma. These heterogeneous tumor cells are strongly positive for TP53 and can also be shed and undergo extensive extrauterine metastasis. The prognosis of patients with plasmacytoma is dependent on clinical staging after surgery and requires clinical management as plasmacytoma.

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• Transparent cell carcinoma
  

Transparent cells are characterized by the presence of polygonal or spike-like cells with clear cytoplasm and, in a few cases, eosinophilic cytoplasm, which are arranged in tubular vesicles, papillae, or solid structures. Extracellular dense eosinophilic spheres or hyaline vesicles are seen in approximately 2/3 of cases. Clear cell carcinoma tends to be highly malignant and is no longer histologically differentiated.

grade, often with advanced lesions at the time of diagnosis.

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• Undifferentiated and dedifferentiated carcinoma
  

Endometrial undifferentiated carcinoma is an epithelial malignancy with an obscure direction of differentiation. The cells lack adhesion and are relatively uniform in size, small to medium in size, arranged in sheets without any obvious nest-like or trabecular structures and without glandular structures. Polymorphic nuclei may occasionally be seen in the background. The dedifferentiated carcinoma consists of a mixture of undifferentiated carcinoma and FIGO grade 1 or 2 endometrioid carcinoma. The differentiated endometrioid component is usually lining the surface of the uterine cavity, while the undifferentiated carcinoma component grows beneath it. The more malignant component determines the patient’s prognosis.

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• Mixed endometrial adenocarcinoma
  

It is endometrial cancer with a mixture of 2 or more pathological types.

At least 1 type of endometrial carcinoma is type II, and the presence of a mixture of any proportion of type II endometrial carcinomas is diagnostic of mixed carcinoma. The most common type is a mixture of endometrial cancer and plasmacytoma, followed by a mixture of endometrial cancer and clear cell carcinoma. The prognosis of mixed carcinoma depends on the component of high-grade carcinoma in the mixed component, even if less than 5 of plasmacytoma The prognosis is still poor even if less than 5 plasmacytoma is mixed in a common type of endometrioid adenocarcinoma. The pathology report should detail the tissue type and proportion of each type of tumor when a diagnosis of mixed carcinoma is made.

Other less common types such as mesonephric ductal adenocarcinoma are adenocarcinomas that originate from the remnants of the mesonephric duct. Primary squamous cell carcinoma is a carcinoma consisting only of cells with squamous cell differentiation. Primary gastric (gastrointestinal) mucinous carcinoma is a carcinoma with mucinous gastric/gastrointestinal features. Neuroendocrine tumors as having neuroendocrine morphology

A heterogeneous group of tumors with neuroendocrine morphology, divided into two major groups: low-grade neuroendocrine tumors, neuroendocrine tumors grade 1 or 2, morphologically the same as those occurring in the stomach and other The former resembles small cell lung cancer, while the latter has large, polygonal cells with vacuolated or deeply stained nuclei, a single prominent nucleolus, high mitotic activity, and extensive map-like necrosis.

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• Uterine carcinosarcoma
  

Originally classified as a sarcoma, but based on clonality studies, it is now considered to be a sarcoma of saprophytic origin. Carcinosarcomas are biphasic tumors composed of high-grade carcinomatous and sarcomatous components, and studies have shown that the sarcomatous component is a result of epithelial

-Mesenchymal transition is derived from carcinoma, and both share the same genetic alterations, with the carcinomatous component most often showing endometrioid or plasmacytic differentiation, and a small proportion showing clear cell carcinoma and undifferentiated carcinoma. The mesenchymal component is most often composed of high-grade sarcomas, with a small proportion showing heterogenous components (including rhabdomyosarcoma, chondrosarcoma, but rarely osteosarcoma). Deep myxomatous and lymphovascular invasion is present in 30% to 40% of tumors. Sarcomas with cancer metastases are morphologically diverse, but most metastases contain a cancerous component. Most cases are characterized by TP53 mutations, similar to endometrial plasmacytoma. Mutations usually associated with endometrial-like endometrial carcinoma are less common. Therefore, most carcinosarcomas are classified in the P53 mutation group, and a small number are classified in the low copy number group.

<5% of endometrial carcinosarcomas are in the POLE mutation group or mismatch repair-deficient group.

The pathology report of endometrium emphasizes standardization and standardization. The content should include the degree of tumor differentiation, histologic type, depth of infiltration, extent of invasion (whether or not it invades

invasion of the interstitial cervical canal, parametrium, adnexa, vagina, bladder, rectum, etc.), cervical or vaginal margins, parametrial margins, and lymph node metastases [for detection of micro-metastases, sentinel lymph nodes should be tested for hyperstaging; isolated The N0 (i+) stage of isolated tumor cells should be considered in the discussion of adjuvant therapy], immunohistochemistry, and molecular pathology indexes. In addition, units with diagnostic capabilities should also be accompanied by results of molecular typing and other molecular markers associated with drug-targeted therapy for endometrial cancer (e.g., HER2 testing is recommended for advanced or recurrent plasma endometrial cancer), biological behavior, mismatch repair genes, and determination of prognosis for clinical reference.

III.

Surgical-pathological staging can reflect the metastatic and infiltrative status of endometrial cancer more comprehensively and accurately, and thus formulate the correct postoperative treatment plan and facilitate the comparison of efficacy among different cancer treatment centers. The current surgical pathological staging criteria published by FIGO in 2009 are used (Table 1).

Table 1 FIGO staging of endometrial cancer (2009)

(surgical pathology staging)

< colgroup>

IIIBa	Vaginal and/or parametrial involvementc
IIICa IIIC1a IIIC2a	pelvic lymph node and/or para-aortic lymph node metastasisc Pelvic lymph node positive Positive para-aortic lymph nodes and/or positive pelvic lymph nodes
IVa	Tumor invasion of bladder and/or rectal mucosa, and/or distant metastases
IVAa	Tumor invading bladder and/or rectal mucosaa
IVBa	Distant metastases, including intra-abdominal and/or inguinal lymph node metastases

 

a any G1, G2, G3.

b Involvement of the cervical duct glands should be considered stage I and beyond that stage II c Positive cytology must be reported separately, but does not change the stage

IV.

Treatment principles of endometrial cancer: The treatment of endometrial cancer is mainly surgery, supplemented by radiation therapy (radiotherapy), chemotherapy (chemotherapy) and hormone therapy. The treatment plan should be based on the pathological diagnosis and histological type, as well as the patient’s age, general condition, contraindications to surgery, and medical comorbidities. Surgery is the main treatment for endometrial cancer. Except for patients who cannot tolerate surgery or are too advanced to be operated, comprehensive staged surgery should be performed. For patients with severe medical complications and advanced age who are not suitable for surgery, radiotherapy and drug therapy can be used. The indications for various treatment methods should be strictly followed to avoid over-treatment or under-treatment. Planned and rational comprehensive treatment is emphasized, and individualized treatment is valued.

(i) Surgical treatment.

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• Comprehensive staging surgery and adjuvant treatment modality selection
  

The principles of surgical staging for endometrial cancer: (1) electrocoagulation or clamping of the isthmus of the fallopian tubes at the corners of the uterus bilaterally after abdominal entry to avoid intraoperative spread of intrauterine tumors through the fallopian tubes to the pelvis. (2) Complete exploration of the entire abdominal cavity to the pelvic cavity should be performed to fully evaluate the peritoneum, diaphragm, and plasma surface for lesions, and biopsy should be taken at any suspicious site to exclude extrauterine lesions. (iii) Cytology of ascites or cytology of pelvic and abdominal washings is still recommended and reported separately. (iv) Total hysterectomy + bilateral adnexal resection and lymph node evaluation is the most basic surgical procedure for those with lesions confined to the uterus, and palliative total hysterectomy with bilateral adnexal resection is possible in some patients with unresectable metastases. 5 The procedure can be performed transabdominally, transvaginally, or laparoscopically or robotically, with complete removal of the uterus, avoiding the use of crushers and removal of the uterus in pieces. Minimally invasive surgery can be the first choice, with fewer surgical complications and faster recovery. (6) Lymph node evaluation includes pelvic ± para-aortic lymph nodes. In cases where the lesion is confined to the uterus and there are no lymph node abnormalities, lymph node dissection is also an important part of the staging procedure, and lymph node dissection can determine the prognosis and provide a basis for subsequent treatment. However, if there are suspicious or enlarged lymph nodes, they must be removed to exclude metastasis and to clarify the pathology. (vii) Lymph node evaluation can be performed by pelvic lymph node dissection. However, if there is deep muscle infiltration, or if the pathology is high-grade carcinoma, plasmacytoid adenocarcinoma, clear cell adenocarcinoma, or carcinosarcoma, parietal lymph nodes should be removed. (8) Patients with endometrial cancer with lesions confined to the body of the uterus and no evidence of extrauterine metastasis on imaging may be considered for biopsy of the anterior lymph nodes. The patient may be considered for anterior lymph node biopsy.

After hysterectomy, the uterus should be examined by dissection and, if necessary, pathologic examination by frozen section. The uterus should be dissected after removal during surgery, and the surgical record should clarify the size and location of the cancerous tumor

(uterine fundus or lower uterine segment/cervical), depth of myometrial infiltration (as a proportion of the whole myometrium), and whether the isthmus of the cervix and bilateral adnexa are involved.

Pathologically or MRI confirmed endometrial cancer invading the cervical mesenchyme (stage II), extrafascial hysterectomy/modified extensive hysterectomy + bilateral adnexal resection + pelvic and para-aortic lymph node dissection is an option.

Suspected tumor spread outside the uterus: if the lesion is beyond the uterus but confined to the peritoneal cavity (including positive ascites cytology, greater omentum, lymph nodes, ovaries, and peritoneal metastases), cytoreductive surgery including hysterectomy + bilateral adnexal resection should be performed to remove as much of the visible tumor as possible, aiming for no visible residual tumor. The tumor should be removed as much as possible to achieve no residual tumor. The goal of total hysterectomy + bilateral adnexal resection + surgical staging + tumor reduction is to achieve the absence of visually measurable lesions as much as possible; neoadjuvant chemotherapy can also be considered before surgery. For lesions beyond the uterus but confined to the pelvis (metastases to the vagina, bladder, bowel, parametrium, lymph nodes) that cannot be surgically removed, external irradiation therapy and/or vaginal brachytherapy ± systemic therapy is indicated, or chemotherapy alone may be followed by reassessment for surgical treatment, or radiotherapy may be chosen depending on the outcome of treatment. If the lesion is beyond the abdominal cavity or has metastasized to the liver, chemotherapy and/or external irradiation and/or hormonal therapy may be indicated, and palliative hysterectomy + bilateral adnexal resection may also be considered.

• Type II endometrial cancer: including plasmacytoma, clear cell carcinoma, and carcinosarcoma. Its treatment follows the principles and modalities of surgery for ovarian cancer. Besides including cytological examination of ascites, total hysterectomy of both adnexa and resection of pelvic lymph nodes and para-aortic lymph nodes, large omentum resection and multi-point biopsy of peritoneum should be performed. In case of advanced stage, tumor cytoreductive surgery will be performed. The surgical pathological stage and the application of adjuvant therapy, such as systemic therapy and radiotherapy, should be clarified according to the postoperative pathology. Inability to surgically excise
  

For those who cannot be surgically removed, they can be re-evaluated for surgical treatment after chemotherapy alone, or external radiation therapy and/or vaginal brachytherapy. The patient may be re-evaluated for surgery after chemotherapy alone, or external radiation therapy and/or vaginal brachytherapy ± systemic therapy, or radiation therapy depending on the outcome of treatment.

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• Several special issues
  

• Total hysterectomy with double adnexa is the main treatment for endometrial cancer confined to the body of the uterus. It can be performed open, transvaginal or laparoscopic, or robotic laparoscopic techniques. However, the use of crushers and removal of the uterus in pieces should be avoided. Uterine fragmentation can lead to tumor spillage and increase the risk of local or abdominal recurrence.
  
• Lymph node dissection and anterior lymph node biopsy to assess lymph node status are important components of a fully staged procedure. component. In clinical stage I, most metastases are histologic rather than naked-eye metastases, so systemic lymph node dissection is recommended. For any of the following conditions: (i) positive pelvic lymph nodes; (ii) deep muscle infiltration
  

  ③G3; ④Plasmacytoid adenocarcinoma, clear cell adenocarcinoma, or carcinosarcoma requires evaluation of pelvic lymph nodes and at least submesenteric artery level (preferably to the level of renal vessels) of abdominal Para-aortic lymph nodes. Selective subregional lymph node sampling or localization of anterior lymph nodes may sometimes be performed depending on the patient’s condition. If there is significant enlargement of retroperitoneal lymph nodes and metastases are suspected, intraoperative frozen pathology is indicated to clarify the diagnosis and determine the lymph node surgery. For patients with preoperative comprehensive assessment of lesions confined to the endometrial layer or superficial myometrium and with highly or moderately differentiated endometrial cancer, the probability of lymph node metastasis is low and the need for lymph node dissection is controversial.

  A prospective randomized study found that the extent of lymph node dissection in early endometrial cancer was not associated with survival. img src=”https://www.kiraspecialist.com/wp-content/uploads/2022/06/062222_1020_202231.png” alt=””/>Patients with endometrial cancer who undergo lymphatic dissection will have

present with lower extremity lymphedema. Prospective and retrospective studies have confirmed that in patients with endometrial cancer confined to the body of the uterus, anterior lymph node dissection with concomitant ultrastaging detection increases the rate of metastatic lymph node detection and has a lower false-negative rate than systematic lymph node dissection; therefore, anterior lymph node dissection is gradually becoming a method of surgical staging, and the uterine cervix has proven to be the most effective injection site for detecting lymph node metastasis in endometrial cancer, and it is recommended Both superficial (1 to 3 mm) and deep (1 to 2 cm) cervical injections are used. Colloidal technetium-99m (99mTc) is most commonly used for radiolabeling, and commonly used biological dyes include1 Isosulfur Blue,1
Methylene Blue, 2.5 Patented Blue, Indocyanine Green as a new emerging The NCCN guidelines recommend considering sentinel lymph node biopsy as an alternative to systemic lymph node dissection for endometrial cancer with lesions confined to the uterus.

• Preservation of ovaries in young patients with endometrial cancer: The incidence of endometrial cancer is trending younger, and in young patients, if ovarian preservation is requested, the following criteria must be met For young patients, if ovarian preservation is requested, the following conditions must be met: (i) age <40 years; (ii) patient requests ovarian preservation; (iii) stage IA, highly differentiated; (iv) negative cytology of abdominal irrigation fluid; (v) no suspicious lymph node metastasis on preoperative and intraoperative evaluation; and (vi) follow-up conditions are available.
  

  3. Surgical complications and management: The main complications of transabdominal total hysterectomy or extensive hysterectomy are injuries to peripheral organs such as ureter, bladder, and rectum. Careful dissection should be performed intraoperatively to avoid injury. Once they occur, procedures such as ureteral stenting and organ repair need to be performed promptly. Complications of laparoscopic surgery are mainly vascular, intestinal and bladder injuries and subcutaneous emphysema, in addition to perforator hernia. The incidence of laparoscopic perforator hernia has been reported in the literature to be 0.2 to 3.1 , and suturing of the fascial layer for perforations larger than 10 mm in diameter may reduce the incidence of hernias. Others and

Occurrences include bleeding (abdominal bleeding, vaginal stump bleeding), infection (urinary tract, pelvic/abdominal, lymphatic cyst infection, etc.), intestinal obstruction, incisional dehiscence, thrombosis and embolism, and in a few cases, tumor implantation and metastasis may occur. Strict aseptic and tumor-free operation is required during the operation. Pay attention to effective and firm suturing and ligation. Postoperative antimicrobial drugs should be used prophylactically and postoperative care should be paid attention to.

(ii) Radiation therapy.

Except for inoperable endometrial cancer, radical radiotherapy, including extracorporeal radiotherapy combined with brachytherapy, is feasible. Radiotherapy is often used as an adjuvant treatment for postoperative patients in endometrial cancer.

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• Extracorporeal radiotherapy
  

For the primary tumor and metastatic solid tumor sites in the pelvis, also include the common, external, internal, and closed lymph node drainage areas, the parametrium, and the upper vaginal and paravaginal tissues, as well as the presacral lymph node area in cases of cervical involvement. In cases of para-abdominal aortic lymph node involvement, an extended field is irradiated, including the common iliac and para-abdominal aortic lymph node regions. The NCCN guidelines recommend radiation planning using CT image-based multifield conformal techniques or intensity-modulated conformal radiotherapy techniques, with attention to quality verification and organ movement during fractionated irradiation (see the section on external radiotherapy for cervical cancer).

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• Short-range radiotherapy
  

There is no accepted dose reference point for conventional intracavitary treatment of endometrial cancer. The endometrial receptivity, the myometrium [5 mm, 10 mm below the endometrium, or the point parallel to the mid-axis of the uterus through point A (A-Line)] is used as the dose reference point.

Treatment planning based on three-dimensional imaging is now recommended, and the dose of radiotherapy is individualized according to the actual clinical tumor. In 2015, the American Brachytherapy Association proposed a definition of CT- or MRI-guided radical radiotherapy target areas for endometrial cancer. The tumor zone is primarily the extent of the lesion visible on T2-weighted images in MRI. The clinical target area is the entire body of the uterus, cervix and upper vagina on MRI or CT. The organs at risk need to include the sigmoid colon, rectum, bladder, small bowel, and uninvolved vaginal portions on MRI or CT.

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• Recommendations for postoperative adjuvant therapy
  
  • Endometrioid adenocarcinoma
    

I A (G1-2) is preferred for follow-up and observation, and endoluminal treatment may be considered if there are high-risk factors (presence of lymphovascular interstitial infiltration and/or age ≥60 years).

I A (G3), with preference for intracavitary radiotherapy, or follow-up if there is no lymphovascular infiltration, and consideration of ex vivo radiotherapy if there are high-risk factors (Class 2B evidence).

Ib (G1), prefer intracavitary radiotherapy, or consider follow-up if there are no other high-risk factors.

Ib (G2), intracavitary radiotherapy is preferred and external radiotherapy may be considered if there are risk factors, and some patients may be followed up if there are no other risk factors.

Ib (G3), radiotherapy (external and/or intracavitary radiotherapy) ± systemic therapy

(Systemic Therapy Class 2B evidence).

II: External radiotherapy (preferred) and/or intracavitary radiotherapy ± systemic therapy (systemic therapy category 2B evidence).

III: chemotherapy±extracorporeal radiotherapy±intracorporeal radiotherapy.

Stage IVA-IVB (no or minimal residuals after tumor reduction): chemotherapy±external radiotherapy±intracavitary radiotherapy.

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• Non-endometrioid carcinoma
  

Stage IA, systemic therapy + intracavitary therapy or external radiotherapy ± intracavitary radiotherapy, intracavitary therapy or observation for those confined to the mucosa or without residual lesions.

Stage IB and beyond, combined systemic therapy ± external radiotherapy ± intracavitary radiotherapy

 

Treatment.

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• Treatment techniques and dose recommendations
  

Referring to the NCCN guidelines, treatment options for radiotherapy for endometrial cancer are given, including

 

Extracorporeal radiotherapy and/or brachytherapy. Diagnostic imaging prior to radiotherapy evaluates the extent of the local area of the tumor and the presence of distant metastases. Extracorporeal radiotherapy mainly targets the pelvic cavity including or excluding the para-aortic lymph node region. Brachytherapy is primarily directed at.

1) uterus (in preoperative or radical radiotherapy); and 2) vagina (in adjuvant therapy after total hysterectomy).

Pelvic radiotherapy targets the primary tumor and metastatic solid tumor sites in the pelvis and also includes the general, external, internal iliac, and closed lymph node drainage areas, the parametrium, and the upper vaginal and paravaginal tissues. The anterior sacral lymph node area should also be included in cases of cervical involvement. The extension field should include the pelvic field and also target the common iliac and para-abdominal active lymph node regions. The upper boundary of the extension field depends on the specific clinical situation and reaches at least the level of the renal vasculature. For subclinical lesions in the radiation field a dose of 45-50 Gy, with simultaneous or sequential dosing of 10-20 Gy in the presence of solid tumors or enlarged lymph nodes, taking into account the normal tissue limit, may be used. Radiotherapy planning with multiple conformal field techniques based on CT images is recommended (see the section on external 3D radiotherapy for cervical cancer).

The dose of brachytherapy also depends on the specific clinical stage and tumor status of the patient. If the cervix is involved, the A-point dose should be considered in addition to the myometrial dose reference point. The total dose of A-point radiotherapy for cervical cancer can be referred to. If MRI images are used for brachytherapy, the total EQD2 dose in the tumor area is ≥ 80 Gy. Depending on the stage, the total bioequivalent dose in the tumor area and the clinical target area is 80-90 Gy and 48-75 Gy, respectively, in combination with external radiotherapy, while the limited organ-threatening recommendations are sigmoid and rectal D2cc: no more than 70 to 75 Gy, bladder D2cc: 80 to 100 Gy, and intestinal D2cc: 65 Gy.

For postoperative adjuvant radiotherapy, brachytherapy can be started as soon as the vaginal stump is healed, usually within 12 weeks after surgery. The dose reference point is at the surface of the vaginal mucosa or 0.5 cm below the mucosa, targeting the upper vaginal segment. High dose rate brachytherapy. For those who supplement brachytherapy with external radiotherapy, the usual dose is 4 to 6 Gy

×2 to 3f (mucosal surface). For postoperative brachytherapy-only supplementation, the usual regimen is 7Gy×3f (0.5 cm below the mucosa), 5.5Gy×4f (0.5 cm below the mucosa), or 6Gy×5f (at the mucosal surface).

(iii) Systemic chemotherapy and hormone therapy.

• Systemic chemotherapy: Systemic chemotherapy should be used mainly in patients with advanced (FIGO staging III-IV) or relapsed disease and in patients with specific pathological types. For patients in the high-risk group of stage IB, G3 , NCCN guidelines also recommend postoperative adjuvant chemotherapy to improve prognosis, but only for category 2B recommendations.
  

  Systemic chemotherapy is recommended in combination with chemotherapy regimens. The recommended chemotherapy regimens and drugs are as follows: carboplatin/paclitaxel, cisplatin/doxorubicin, cisplatin/doxorubicin/paclitaxel (not widely used because of greater toxicity), carboplatin/docetaxel, carboplatin/

Paclitaxel/Bevacizumab,Isocyclophosphamide/Paclitaxel (for carcinosarcoma, Class I evidence),Cisplatin/Isocyclophosphamide (for carcinosarcoma, Class I evidence) (for carcinosarcoma), everolimus/letrozole (endometrioid adenocarcinoma), carboplatin/paclitaxel/trastuzumab (HER-2-positive plasmacytoma). If patients cannot tolerate combination chemotherapy, single agents such as cisplatin, carboplatin, doxorubicin, epirubicin liposomes, paclitaxel, albumin paclitaxel, topotecan, bevacizumab, docetaxel (level 2B evidence), and isocyclophosphamide (for carcinosarcoma) are available as alternative chemotherapy regimens.

The commonly used drug regimens for endometrial cancer are shown in Table 2.

Table 2 Common protocols for endometrial cancer

Liposomes), paclitaxel (or albumin-bound paclitaxel), topotecan, bevacizumab, docetaxel, isocyclophosphamide (for carcinosarcoma), tamsulosin Hormone therapy (mainly for G1 to 2 endometrioid carcinoma) Medroxyprogesterone acetate/tamoxifen (alternating) Medroxyprogesterone/tamoxifen (alternating)
Medroxyprogesterone acetate Medroxyprogesterone
Tamoxifen Toremifene Letrozole Anastrozole Fulvestrant
Levonorgestrel extended-release system (for selected patients who need to
preservation of reproductive function)
Targeted therapies: Immune checkpoint inhibitors and tyrosine kinase inhibitors are novel targeted therapeutic agents that have demonstrated antitumor activity in molecular marker-based second-line treatment of endometrial cancer. Pabrolizumab was used in the second-line treatment of unresectable or metastatic, highly microsatellite unstable or mismatch repair-deficient endometrial cancer, with a single-agent objective remission rate of 57.1, recommended by NCCN guidelines since 2018. The study found that lenvatinib combined with pablizumab to treat
 

Total 24-week outcomes for patients with advanced endometrial cancer who were previously treated with systemic therapy

The objective remission rate in the body population was 38, and its objective remission rate at 24 weeks for microsatellite stable patients was 36.2. Based on these results, the 2019 NCCN guidelines recommend the combination of lenvatinib + pablizumab for the treatment of patients with advanced endometrial cancer who have progressed after prior systemic therapy, are not candidates for radical surgery or radiation therapy, and are not highly microsatellite unstable/mismatched repair deficient.

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• Hormone therapy
  

Recommended medications for hormone therapy include high-dose high potency progestin, tamoxifen

(the two can be used interchangeably), aromatase inhibitors, and fulvestrant. Hormone therapy is used only for well-differentiated endometrioid adenocarcinoma, for young patients with early-stage endometrial cancer who need to preserve reproductive function and for patients with advanced, recurrent, or inoperable disease. Highly effective drugs, high doses and long courses of treatment are preferred. It is more effective in patients with well-differentiated tumors and positive progesterone receptors, and it is more effective in patients with distant recurrence than in those with pelvic recurrence. The duration of treatment is not yet standardized, but it should be applied for at least 6 months. The overall effective rate is 25 to 30 . The most commonly used progestins include (1) medroxyprogesterone acetate, 500-1000 mg orally daily, and (2) megestrol acetate, 160 mg orally daily. Routine postoperative hormone therapy is not recommended for early-stage patients. For patients who fail standard progestin therapy, tamoxifen has a remission rate of approximately 20. Tamoxifen may also be used interchangeably with progestin. For patients with disease progression after hormone therapy, systemic chemotherapy is an option.

(iv) Combination therapy.

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• Adjuvant therapy after surgery
  

Postoperative treatment for stage I patients needs to be evaluated based on the presence or absence of high-risk factors in the patient.

High-risk factors include age >60 years, deep myeloid infiltration, lymphovascular interstitial infiltration, hypofractionation, and high-risk tissue type. Complementary treatment is based on radiotherapy, which is initiated as soon as possible after the vaginal stump has healed, preferably no later than 12 weeks after surgery. The GOG249 study also introduced a further subset of high and intermediate risk factors to assess Postoperative radiotherapy was administered or not. For example, patients aged 50 to 69 years with two risk factors, or aged 50 years with three risk factors, or aged ≥70 years with one risk factor. Extracorporeal radiotherapy is feasible for these patients. Risk factors include histologic grade 2 or 3, invasion of the deep muscle layer (outer 1/2 muscle layer), and lymphovascular interstitial infiltration. The postoperative management of stage II patients needs to be supplemented with radiotherapy ± chemotherapy in conjunction with the surgical approach and the presence of high-risk factors. Stages III-IV: Treatment needs to be individualized. Usually, total hysterectomy with full staging is required for those who are suitable for surgery; for those with large tumors, maximum reduction is required. Postoperatively, systemic therapy ± external irradiation is administered depending on the stage, extent of tumor invasion, and residual tumor.

±vaginal brachytherapy. See the recommendations for postoperative adjuvant therapy in the Radiotherapy section.

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• Follow-up treatment for incomplete surgical staging/unexpected detection of endometrial cancer
  

Incomplete surgical staging mostly refers to failure to remove both ovaries or failure to perform lymph node dissection. The treatment is as follows: ① Stage IA/G1 to 2 grade/no lymphovascular interstitial infiltration/age

<60 years of age, or stage IA/GGrade 3 /No myelopathic infiltration/No lymphovascular interstitial infiltration/ Age<60 years of age can be observed postoperatively. ②Stage IA/GGrade 3 or Stage IB/GGrade 1 to 2 with age ≥60 years and lymphovascular interstitial infiltration(-) may be selected for imaging first, and if the imaging result is negative, then vaginal brachytherapy will be performed. If the imaging result is negative, then vaginal brachytherapy will be performed. (iii)
span style=”font-size:14pt”>Stage IB/G1 to 2 Grades/Lymphovascular Interstitial Infiltrate (+), Stage IB/G3 If the imaging result is negative, treat according to the corresponding plan after complete surgical staging; if the imaging result is suspicious or positive, treat according to the corresponding plan after complete surgical staging. If imaging is suspicious or positive, re-surgical staging or pathologic confirmation of metastatic lesions is performed in appropriate patients; re-surgical staging can also be chosen directly, with the same postoperative adjuvant treatment options as described above for full surgical staging.

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• Treatment of Recurrent Endometrial Cancer
  

The recurrence rate after surgery in stage I and II patients is about 15, with 50 to 70 of the compound

Recurrence is symptomatic. Most recurrences occur within 3 years of treatment. Relapses that are confined to the vagina or pelvis continue to have a good outcome with treatment. Isolated vaginal recurrences have a 5-year survival rate of 50 to 70 after radiotherapy. https://www.kiraspecialist.com/wp-content/uploads/2022/06/062222_1020_202248.png” alt=””/>. Recurrence beyond the vagina or pelvic lymph nodes is associated with a poorer prognosis. Treatment after recurrence correlates with the location of the recurrence and whether previous radiation therapy was received.

Local recurrence without distant metastases confirmed by imaging: 1) external irradiation therapy ± vaginal brachytherapy or surgical exploration + resection ± intraoperative radiotherapy for those who have not received prior radiotherapy at the location of recurrence. If the lesion is found to be confined to the vagina after surgery, external irradiation therapy ± vaginal brachytherapy ± systemic therapy is feasible; if the lesion is found to extend beyond the vagina and reach the pelvic lymph nodes after surgery, external irradiation therapy ± vaginal brachytherapy ± systemic therapy is feasible, and if it reaches the para-aortic or common iliac lymph nodes, external irradiation therapy ± systemic therapy is performed. If the recurrence reaches the upper abdomen and the residual lesion is small, systemic therapy ± external irradiation therapy can be chosen. Huge recurrent lesions are treated as follows for disseminated lesions. ② Those who have received prior radiotherapy at the location of recurrence, if they originally received only

Vaginal brachytherapy is treated in the same way as for those who have not received prior radiotherapy at the site of recurrence. If previously treated with external pelvic irradiation, consider surgical exploration + resection ± intraoperative radiotherapy and/or systemic therapy ± palliative radiotherapy.

Isolated metastases: ① Consider surgical resection and/or external irradiation therapy or ablative therapy. ② Consider systemic treatment. For unresectable lesions or recurrence, treat disseminated lesions as follows.

Disseminated lesions: (i) hormonal therapy for low-grade or asymptomatic or estrogen receptor/progesterone receptor positive, chemotherapy for continued progression, and supportive therapy for further progression after treatment. (2) Chemotherapy ± palliative external irradiation for symptomatic or GGrade 2 to 3 or giant lesions, and supportive therapy for further progression.

(E) Comprehensive treatment of special types of endometrial cancer (plasmacytoma, clear cell carcinoma).

Plasmacytoid adenocarcinoma and endometrial clear cell carcinoma: Plasmacytoid adenocarcinoma of the uterus is less common. The pathological pattern is the same as that of ovarian plasma papillary carcinoma, and is characterized by the presence or absence of papillary structures in plasma carcinoma with sand bodies. It is highly malignant, poorly differentiated, and may develop early vascular infiltration, deep muscle involvement, and pelvic/abdominal lymph node metastasis. The prognosis is poor, with a stage I recurrent metastasis rate of 31 to 50 ; early 5-year survival rate 40～50 and below 15 in the late . The prognosis is also poor for endometrial clear cell carcinoma, both of which are a specific subtype of endometrial cancer (type II).

Treatment principles: Regardless of the early or late stage, the same comprehensive surgical staging as for ovarian cytoreductive reduction should be performed, including pelvic/abdominal washout cytology, total hysterectomy, pelvic lymph node and para-aortic lymph node dissection, greater The procedure includes pelvic/abdominal washout cytology, total hysterectomy, pelvic lymph node and para-aortic lymph node dissection, large omentectomy and multi-point biopsy of the peritoneum. In advanced stages, tumor thinning is performed

Cell reduction. For stage IA patients, the postoperative options are: 1) chemotherapy + endovenous radiotherapy

(preferred); (ii) external radiotherapy ± intratumoral radiotherapy; (iii) intratumoral radiotherapy alone for some patients whose tumors do not invade the muscular layer; and (iv) follow-up. For patients with stage IB-IV, chemotherapy±external radiotherapy±intracavitary radiotherapy can be chosen. The American Gynecologic Oncology Group compared the response of plasmacytoma, clear cell carcinoma and endometrioid carcinoma to chemotherapy and found no significant difference. However, it is generally accepted that the same chemotherapy regimen as that for ovarian plasmacytoma, such as paclitaxel + carboplatin, should be used after surgery for plasmacytoma of the uterus. In patients with advanced disease, preoperative neoadjuvant chemotherapy followed by tumor cytoreductive surgery can be used, followed by chemotherapy.

Uterine carcinosarcoma: Pathologists consider uterine carcinosarcoma to be a chemosarcoma, which should be an epithelial carcinoma, and therefore was classified as endometrial carcinoma by the WHO in 2003 and endometrial carcinoma type II by the NCCN pathology classification in 2010. It is highly malignant and can develop abdominal, lymphatic, and bloodstream metastases at an early stage.

Treatment principles: The overall principles of treatment are the same as those described above for plasmacytoma and clear cell carcinoma. Previously, isocyclophosphamide was considered to be the most effective single agent for endometrial carcinosarcoma. Phase III clinical studies have shown that paclitaxel combined with isocyclophosphamide significantly prolonged the overall survival time of patients with sarcoma of uterine cancer compared with isocyclophosphamide alone. Therefore, this combination regimen is recommended by the NCCN guidelines as Class 1 evidence for chemotherapy in uterine carcinosarcoma. However, considering the toxic side effects of isocyclophosphamide and the studies showing that paclitaxel combined with carboplatin is also effective in uterine carcinosarcoma, the NCCN currently prefers to recommend paclitaxel combined with carboplatin as the preferred regimen. Postoperative pelvic irradiation may be effective in controlling recurrence and improving survival.

(vi) Indications and methods for patients with preserved reproductive function.

About 5 of patients with endometrial cancer are diagnosed before age 40. Endometrial pathology is necessary for patients with fertility needs who require preservation of fertility (hysteroscopy is recommended), and hysteroscopy is more reliable, with only 23% of G1 lesions having elevated grade. Enhanced MRI should also be performed to assess the depth of myofibrotic infiltration.

Preservation of fertility is only indicated for endometrioid adenocarcinoma. All of the following conditions are met to preserve reproductive function: 1) Pathological type of endometrioid adenocarcinoma, grade G1, as verified by pathologists in the segmental scraping specimen. (ii) MRI examination (preferred) or transvaginal ultrasonography revealed a lesion confined to the endometrium. ③No suspicious metastatic lesions were found on imaging. ④No contraindication to drug therapy or pregnancy. ⑤ After adequate explanation, the patient understands that preservation of reproductive function is not the standard treatment for endometrial cancer and consults a reproductive specialist prior to treatment. (6) Genetic counseling or genetic testing is performed for appropriate patients. (7) Treatment with megestrol, medroxyprogesterone acetate and levonorgestrel intrauterine extended-release system are available. The most commonly used oral progestins include medroxyprogesterone acetate (250-600 mg/d orally) or medroxyprogesterone acetate (160- 480 mg/d orally). If the endometrial cancer persists for 6-12 months, total hysterectomy + bilateral adnexal resection + surgical pathological staging will be performed, and preoperative MRI may be considered; if the lesion is in complete remission after 6 months, the patient will be encouraged to conceive, and endometrial sampling will be performed every 3-6 months before conception; if the patient has no reproductive plan for the time being, she will be given progestogen maintenance therapy If the patient is not planning to have children, progesterone maintenance therapy and regular monitoring will be provided. After completion of childbirth or if endometrial sampling reveals disease progression, total hysterectomy + bilateral adnexal resection + surgical pathological staging will be performed. Many uteruses

Young patients with endometrioid carcinoma have other factors that affect fertility, including obesity and polycystic ovary syndrome, and weight loss is strongly recommended. Consultation with an infertility specialist may be necessary for a successful pregnancy. Some assisted reproductive techniques may need to be applied after the patient’s hormone therapy, including clomiphene citrate, artificial insemination, and in vitro fertilization.

(vii) Traditional Chinese medicine treatment.

TCM is based on a holistic concept and implements evidence-based treatment, which helps endometrial cancer patients recover from postoperative functions, reduce the adverse effects of radiotherapy and chemotherapy, enhance the effects of radiotherapy and chemotherapy, improve the immunity of the body, reduce the occurrence of complications, and improve cancer It also plays a role in preventing tumor recurrence and metastasis and prolonging the survival period. It can be used in conjunction with Western medicine to complement and complete the treatment of endometrial cancer.

In Chinese medicine, endometrial cancer is mainly caused by the accumulation of phlegm, dampness, heat, and toxicity in the uterus, blocking the meridians, damaging the flushing vessels, and causing accumulation over time, depleting Qi and blood and damaging the internal organs. The main treatment method is to regulate the flushing and the perineum, clear heat, dampness and detoxification, and remove phlegm and silt. In late stage patients, the main treatment is to nourish Yin and nourish the kidney, to consolidate the flushing and stop the bleeding. In recent years commonly used modern Chinese medicinal preparations, including Xihuangwan, Pingxiao capsule, Dahuang Eupatorium pill, Compound Bambusa capsule and Compound Bitter Ginseng injection for the treatment of endometrial cancer, have been widely used in clinical practice with certain efficacy and good safety and tolerability, but these drugs are still lacking high-level evidence-based medical evidence support and need active in-depth research.

V. Prognosis

The prognostic factors influencing endometrial cancer and the stage are clearly related. High-risk factors affecting prognosis in early-stage patients include deep muscle involvement, lymphatic gap involvement, tumor

poor differentiation (G3), specific tumor type, and cervical involvement. The most important postoperative prognostic factor is the presence or absence of lymph node metastasis, i.e., improved surgical pathological staging. Tumor grading and depth of myometrial involvement respond to the probability of lymph node metastasis, and lymphatic gap involvement increases the probability of lymph node metastasis. For malignant tumors with squamous cell component, the invasiveness of the tumor is mainly related to the degree of differentiation of the glands therein. In contrast, type II endometrial cancer has a worse prognosis than type I endometrial cancer.

VI. Follow up

Patients will be followed up every 3 to 6 months for the first 2 to 3 years after completion of treatment and every 6 to 12 months thereafter. Follow-up visits include health education on possible recurrent symptoms, lifestyle, obesity, exercise, smoking cessation, nutritional counseling, sexual health, use of vaginal dilators and vaginal lubricants; follow-up examinations if CA125 is elevated at the time of initial treatment; and imaging examinations if clinically indicated. Because the asymptomatic vaginal recurrence rate is only 2.6 for stage I patients, postoperative asymptomatic patients vaginal cytology is not recommended.

Attachments

Guidelines for the Treatment of Endometrial Cancer (2022 Edition): Validation Expert Group

(in order of surname stroke)

 

Group leader: Lang Jinghe

Members: Wang Danbo, Wang Jianliu, Wang Jianhua, Wang Li, Wang Jing, and

Jiangyu Liu, Jihong Liu, Jiusheng An, Xiaoguang Li, Jiaxin Yang, Lingying Wu, Danhua Shen, Clang Shen, Yan Song, Fuquan Zhang

Xinping Cao, Xing Xie