16. Appendix – Endometrial Cancer

3.3

3.3

modified

A reduction in endometrial cancer risk was observed with continuous combined hormone replacement therapy with conjugated equine estrogens and medroxyprogesterone acetate as progestin with an average duration of use of 5.6 years.

Using progesterone or dydrogesterone as part of -combined hormone replacement therapy, an increase in the risk of developing endometrial cancer has been observed when used for more than 5 years.

3.8

3.5

modified

Sequential-combined hormone replacement therapy with a duration of use <5 years and using a synthetic progestin for at least 12-14 days per month may be considered safe with respect to endometrial cancer risk.

No increase in endometrial cancer risk has been observed with the use of sequential combined hormone replacement therapy with a duration of use <5 years and using a synthetic progestin for at least 10 days per month.

3.15

3.13

modified

A positive family history of endometrial cancer and/or colon cancer is associated with an increased risk of developing endometrial cancer.

Hereditary predisposition in the setting of Lynch syndrome or Cowden syndrome increases the risk of endometrial cancer.

4.6

4.6

modified

In asymptomatic patients on tamoxifen therapy, transvaginal ultrasonography should not be performed for early detection of endometrial carcinoma.

In asymptomatic patients on tamoxifen therapy, transvaginal ultrasound examination for early detection of endometrial carcinoma should not be performed. This also applies to prolonged therapy over 10 years.

4.8

4.8

modified

In women with premenopausal abnormal uterine bleeding without risk factors (suspicious cytology, obesity, Lynch syndrome, diabetes, polyps, etc.), conservative therapy should be attempted first unless the bleeding is hemodynamically relevant. If conservative therapy fails, hysteroscopy/abrasio should be performed.

In women with premenopausal abnormal uterine bleeding, pathologic findings that do not pertain to this guideline (e.g., disturbed early pregnancy, cervical pathology, fibroids) should first be excluded clinically and sonographically. In women with endometrial findings without sonographic malignancy criteria and without risk factors (suspicious cytology, obesity, Lynch syndrome, diabetes, polyps), conservative therapy should be attempted initially unless the bleeding is hemodynamically relevant. If conservative therapy fails, hysteroscopy/abrasio should be performed.

4.21

new

Histopathological diagnosis of endometrial carcinoma results from the combination of histomorphological and immunohistochemical parameters and, if necessary, supplementary molecular pathological findings.

4.32

4.23

modified

Mixed carcinomas of the endometrium are defined according to the WHO classification as tumors with two or more histological subtypes, each of which is microscopically detectable in > 5 % within the total tumor extent. The respective percentage of each histological subtype should be stated in the histological report.  

Mixed carcinomas of the endometrium have two or more histologic subtypes according to the WHO classification (2020), with one of these components being either serous or clear cell.

4.25

new

Endometrioid carcinomas are graded according to FIGO. According to WHO, a two-stage grading "low grade" (G1 or G2) and "high grade" (G3) should be preferred. Serous, clear cell, de- or undifferentiated endometrial carcinomas as well as carcinosarcomas are by definition high-grade carcinomas.

4.26

new

Quantification of lymphatic vessel infiltration should be included in the histopathologic report.  Focal lymphatic vessel infiltration is defined as involvement of <3 lymphatic vessels and extensive ("substantial") lymphatic vessel infiltration as involvement ≥ 3 lymphatic vessels.

4.27

new

Because of a potential therapeutic consequence, HER2 status should be determined in serous endometrial carcinoma.

4.29

4.33

modified

The report of findings from a (fractionated) abrasion or an endometrial biopsy should comment on the evidence and type of endometrial hyperplasia. If carcinoma is present, the histological tumor type should be indicated, taking into account the current WHO classification. If tumor tissue is detected in the cervical fraction of a fractionated abrasion, a specific statement should be made on the detection or absence of endocervical stromal infiltration.

The report of findings from a (fractionated) abrasion or an endometrial biopsy should comment on the evidence and type of endometrial hyperplasia. If carcinoma is present, the histological tumor type should be indicated according to the current WHO classification. If tumor tissue is detected in the cervical fraction of a fractionated abrasion, a specific statement should be made on the detection or absence of endocervical stromal infiltration.

4.31

4.34

modified

The report of findings of a hysterectomy specimen in endometrial carcinoma should include the following information: * histological type according to WHO * in case of mixed carcinoma, with indication of the respective percentage of the total tumor * grading * evidence/absence of lymphatic or blood vessel invasion (L- and V-status) * evidence/absence of perineural sheath infiltrates (Pn-status) * Staging (pTNM) * metric indication of depth of invasion in relation to myometrial thickness in mm * three-dimensional tumor size in cm * if vaginal infiltration is present, metric indication of minimum distance to vaginal resection margin * R classification (UICC).  

The report of findings of a hysterectomy specimen in endometrial cancer should include the following information:  histologic type according to WHO (for mixed tumors, components in %) * grading * staging (pT) * evidence/absence of lymphatic or blood vessel invasion (L and V status) * evidence/absence of perineural sheath infiltrates (Pn-status) * metric indication of depth of invasion in relation to myometrial thickness in cm/mm * three-dimensional tumor size in cm/mm * if vaginal infiltration is present, metric indication of minimal distance to vaginal resection margin * R classification (UICC).

4.33

4.35

modified

The ovaries in endometrial carcinoma should be embedded completely, with acquisition of the hilus ovarii. The work-up of the tubes should follow the SEE-FIM protocol.

The refurbishment of the tubes should be based on the SEE-FIM-like protocol.

4.36

new

Routine immunohistochemical analysis of MMR proteins should not be performed in the setting of endometrial hyperplasia.

4.37

new

MSI analysis in endometrial carcinoma should be primarily immunohistochemical.  The primary use of two antibodies (MSH-6 and PMS-2) is possible, with addition of the respective partner antibody (MSH2 or MLH1) in case of negative results.  Immunohistochemical analysis of MMR proteins should be supplemented by molecular pathological methods (MLH-1 promoter methylation, MSI-PCR) according to the indication.  The sole use of molecular pathological methods should not be performed.  Combined analysis by immunohistochemistry and molecular pathology should not be performed routinely.

4.38

new

Every newly diagnosed endometrial carcinoma should be screened for MMR defect/MSI regardless of age and histological subtype.     MMR/MSI analysis thus also serves to identify patients who should be offered human genetic counseling.

4.39

new

In all histologically diagnosed primary endometrial carcinomas, immunohistochemical determination of p53 as well as MMR proteins should be performed.

4.40

new

In G3 or high intermediate, high risk and intermediate risk endometrial cancer, mutational analysis of the exonuclease domain of POLE should be performed.

4.41

new

Molecular classification (P53 and MMR deficiency) should be performed preoperatively, i.e., on the abradate or endometrial biopsy.

4.42

new

POLE mutation analysis can alternatively be performed postoperatively.

4.43

new

In low risk endometrial cancer, IHC determination of L1CAM can be performed.

4.44

new

Molecular typing of endometrial carcinoma should be performed on optimally fixed tissue, i.e. preferably on the abradate. Due to a high concordance rate between abradate and hysterectomy, a repeat determination on the surgical specimen should not be performed if no additional tumor component is detectable on the hysterectomy specimen.

4.34

4.45

modified

As part of the pathological workup of an omentectomy specimen in endometrial carcinoma, at least one representative kerosene block should be examined in the case of macroscopic tumor infiltration.  In the absence of macroscopic tumor infiltration, four to six kerosene blocks (embedding of multiple specimens in one block is possible) should be examined.  Any additional abnormal findings (e.g., intraomental lymph nodes) should be described macroscopically and examined histologically.

At least one kerosene block should be examined from omentectomy specimens with macroscopic tumor infiltration in endometrial carcinoma.  In the case of macroscopically absent tumor infiltration, four to six kerosene blocks (embedding of several specimens in one block is possible) should be examined.  Any additional abnormal findings (e.g., intraomental lymph nodes) should be described macroscopically and examined histologically.

4.36

4.47

modified

Lymph nodes up to approximately 0.3 cm maximum extent should be embedded in toto, and larger lymph nodes should be bisected or lamellated along their long axis and also completely embedded.

Lymph nodes up to approximately 0.2 cm maximum extent should be embedded in toto, and larger lymph nodes should be bisected or lamellated along their short axis and also embedded completely.

4.49

new

Isolated tumor cells in the sentinel LC (<0.2mm) (pN0 (i+) are per se not an indication for adjuvant radiotherapy and/or chemotherapy. This is only recommended in case of corresponding additional risks (e.g. p53 mutation, type II EC, LVSI).

4.50

new

For micrometastases (>0.2 mm, <2mm) (pN1(mi)), adjuvant radiotherapy and/or chemotherapy should be given.

4.39

4.51

modified

The sentinel lymph nodes harvested in studies of endometrial carcinoma are to be fully embedded and examined in staged sections. In addition, immunohistochemical examinations should be performed on sentinel lymph nodes that are negative in HE morphology (so-called ultrastaging).

Sentinel lymph nodes in endometrial carcinoma should be lamellated parallel to their short axis and fully embedded and examined in staged sections. Sentinel lymph nodes that are negative in the hematoxylin-eosin stain should additionally be examined by immunohistochemistry (so-called ultrastaging).

5.1

5.1

modified

Endometrial hyperplasia without atypia should not be treated by hysterectomy.

Simple endometrial hyperplasia without atypia should not be treated by hysterectomy.

5.2

new

Hysterectomy may be considered for complex endometrial hyperplasia without atypia.

5.4

modified

In the presence of atypical hyperplasia, the ovaries may be left in place when performing hysterectomy and bilateral salpingectomy in premenopausal women, provided there is no evidence of a hereditary predisposition to ovarian cancer (e.g., BRCA mutation or certain forms of Lynch syndrome).

5.11

5.12

modified

In the presence of endometrioid EC G1, G2 pT1a, the ovaries may be left in place when performing hysterectomy and bilateral salpingectomy in premenopausal women, provided there is no evidence of hereditary predisposition to ovarian cancer (e.g., BRCA mutation, e.g., Lynch syndrome) and the patient is informed of the risk.

In the presence of endometrioid endometrial carcinoma G1, G2 pT1a, the ovaries may be left in place when performing hysterectomy and bilateral salpingectomy in premenopausal women, provided there is no evidence of hereditary predisposition to ovarian cancer (e.g., BRCA mutation, certain forms of Lynch syndrome) and the patient is informed of the risk.

5.12

5.13

modified

In women with incomplete family planning and endometrial cancer and a desire for fertility preservation, the uterus and adnexa may be left in place if the patient has been informed that the standard treatment almost always leading to cure is total hysterectomy and the patient temporarily forgoes curative treatment of a malignancy on her own responsibility, knowing the potentially fatal consequences (progression of the disease, metastasis), even if a pregnancy is carried to term.

In women with incomplete family planning and endometrioid cT1a without myometrial infiltration, G1, p53-wt and L1CAM-negative endometrial carcinoma and a desire for fertility preservation, the uterus and adnexa can be left in place if the patient has been informed, that the standard treatment almost always leading to cure is total hysterectomy and that the patient temporarily forgoes curative treatment of a malignancy on her own responsibility, knowing the potentially fatal consequences (progression of the disease, metastasis) even if a pregnancy is carried to term.

5.13

5.14

modified

If uterus preservation is desired, the uterus and adnexa can be preserved in the presence of early endometrial carcinoma if the patient has been recommended a consultation with a reproductive physician to assess the chances of fulfilling a childbearing desire.

If uterus preservation is desired, the uterus and adnexa can be preserved in the presence of endometrioid cT1a, without myometrial infiltration G1, p53-wt, and L1CAM-negative endometrial carcinoma if the patient has been recommended a consultation with a reproductive physician to assess the chances of fulfilling a childbearing desire.

5.14

5.15

modified

In cases of desire for uterine preservation and early endometrial cancer, the uterus and adnexa may be left in place if the patient agrees to close monitoring and has been informed of the need for hysterectomy after fulfillment or abandonment of the desire to have children.

If uterus preservation and endometrioid cT1a, without myometrial infiltration G1, p53-wt and L1CAM-negative endometrial carcinoma are desired, the uterus and adnexa can be left in place if the patient agrees to close monitoring and has been informed of the need for hysterectomy after fulfillment or abandonment of the desire to have children.

5.15

5.16

modified

In cases of early endometrial cancer and desire for fertility preservation, the uterus and adnexa may be left in place if a diagnosis of well-differentiated (G1) endometrioid EC expressing progesterone receptors has been made by hysteroscopy with targeted biopsy or with abrasion and evaluation by a pathologist experienced in gynecologic pathology.

In endometrioid cT1a without myometrial infiltration, G1 , p53-wt and L1CAM- negative endometrial carcinoma and desire for fertility preservation, the uterus and adnexa may be left in place if a diagnosis of well-differentiated (G1) endometrioid EC expressing progesterone receptors has been made by hysteroscopy with targeted biopsy or with abrasion and evaluation by a pathologist (m/f/d) experienced in gynecologic pathology.

5.16

5.17

modified

In early endometrial cancer (pT1a, G1) and desire to preserve fertility, the uterus and adnexa can be left in place if laparoscopy with vaginal ultrasound or with MRI has ruled out adnexal involvement or myometrial infiltration as much as possible.

In endometrioid cT1a without myometrial infiltration, G1, p53-wt, and L1CAM-negative endometrial cancer and desire for fertility preservation, the uterus and adnexa may be left in place if laparoscopy with vaginal ultrasound or with MRI has ruled out adnexal involvement or myometrial infiltration as much as possible.

5.17

5.18

modified

In early endometrial cancer and desire for fertility preservation, the uterus and adnexa can be left in place if sufficient drug treatment with medroxyprogesterone acetate or megestrol acetate or a levonorgestrel IUD is given.

In endometrioid cT1a without myometrial infiltration, G1, p53-wt, and L1CAM-negative endometrial cancer and desire for fertility preservation, the uterus and adnexa can be left in place if sufficient drug treatment is given with medroxyprogesterone acetate 200-250 mg/d/p.o.) or megestrol acetate (160-200 mg/d/p.o.)or a levonorgestrel IUD (52 mg).

5.19

5.20

modified

EC patients (pT1a without myometrial infiltration, G1) without a current desire to have children should receive maintenance therapy (levonorgestrel-IUD, oral contraceptives, cyclic progestins) and have an endometrial biopsy every 6 months.

Patients with endometrioid cT1a without myometrial infiltration, G1, p53-wt, and L1CAM-negative endometrial cancer without a current desire to have children should receive maintenance therapy (levonorgestrel-IUD, oral contraceptives, cyclic progestins) and have an endometrial biopsy every 6 months.

5.21

5.22

modified

If uterus preservation is desired, uterus and adnexa can be left in the presence of endometrioid adenocarcinoma of the endometrium cT1A, G1 without evidence of myometrial infiltration, with expression of the progesterone receptor, if the following conditions are met:   * information that the standard treatment almost always leading to cure is total hysterectomy, * consent with close follow-up, * education about the need for hysterectomy after fulfillment or abandonment of the desire to have children, * for confirmatory diagnosis hysteroscopy with targeted biopsy or abrasion, * Laparoscopy with vaginal ultrasound or with MRI to rule out adnexal involvement/myometrial infiltration, * Diagnosis made or confirmed by a pathologist experienced in gynecologic pathology, * Treatment with MPA or MGA or LNG-IUD, * After 6 months, repeat hysteroscopy with abrasio as well as imaging. If no response, hysterectomy, * if complete remission, aim for pregnancy (reproductive physician), * if no current desire to have children: maintenance therapy and endometrial biopsy every 6 months, * after fulfillment or abandonment of desire to have children: recommend total hysterectomy and bilateral adnexal extirpation.  

 If uterus preservation is desired, uterus and adnexa may be left in the presence of endometrioid endometrial cancer (cT1a, G1, p53-wt and L1CAM-negative) if the following conditions are met:  * information that the standard treatment almost always leading to cure is total hysterectomy, * consent with close follow-up, * education about the need for hysterectomy after fulfillment or abandonment of the desire to have children, * for confirmatory diagnosis hysteroscopy with targeted biopsy or abrasion, * Laparoscopy with vaginal ultrasound or MRI to exclude adnexal involvement/myometrial infiltration, * Diagnosis made or confirmed by a pathologist (m/f/d) experienced in gynecologic pathology, * Treatment with MPA or MGA or LNG-IUD (52 mg), * After 6 months, repeat hysteroscopy with abrasio as well as imaging. If no response, hysterectomy, * if complete remission, strive for pregnancy (reproductive physician (m/f/d)), * if currently no desire to have children: maintenance therapy and endometrial biopsy every 6 months, after fulfillment or abandonment of the desire to have children: recommend total hysterectomy and bilateral adnexexstirpation.

6.1

6.1

modified

In endometrial carcinoma cT2 or pT2 (with histologic evidence of involvement of the cervical stroma) without clinical suspicion of parametrial infiltration, radical hysterectomy (parametrial resection) should not be performed.

In endometrial carcinoma cT2 or pT2 (with histologic evidence of involvement of the cervical stroma) without clinical suspicion of parametrial infiltration, radical hysterectomy (parametrial resection) should not be performed.

6.2

modified

In patients with endometrial carcinoma (all stages and histologies), the LK that appear enlarged on laparoscopic or open inspection of the abdominal cavity and/or are palpatorily conspicuous ("bulky nodes") should be removed.

6.4

new

When surgical LK staging is performed in patients with endometrial cancer, it should be performed as a systematic LNE or sentinel node biopsy rather than sampling.

6.4

6.5

modified

In type I endometrial carcinoma (ICD-0: 8380/3, 8570/3, 8263/3, 8382/3, 8480/3) pT1a, G1/2, systematic lymphadenectomy should not be performed for clinically unremarkable LK.

In low risk type I endometrial carcinoma pT1a, G1/2, no bulky nodes, systematic lymphadenectomy should not be performed.

6.6

new

If pT1a (without myometrial infiltration), G1/G2, a p53 mutation (intermediate risk), or L1CAM overexpression (high-intermediate risk) is present in a type I endometrial carcinoma, a sentinel node biopsy can be performed, followed by systematic LNE if necessary.

6.7

new

If type I endometrial carcinoma cT1a, G3, or cT1b, G1/2 and no p53 mutation (i.e., at least one intermediate risk endometrial carcinoma) is present preoperatively, sentinel node biopsy can be performed, followed by systematic LNE if necessary. Primary systematic LNE should be omitted.

6.8

new

In endometrial cancer type I, cT1b, G3 (high-intermediate risk group), surgical LK staging - sentinel LNE or (sentinel-assisted) systematic LNE) should be performed.

6.9

new

If type I endometrial carcinoma cT1a, G3, or cT1b, G1/2 and a p53 mutation (high risk) are present preoperatively, surgical LK staging (sentinel LNE and/or (sentinel-assisted) systematic LNE) should be performed.

6.5

6.10

modified

For endometrial carcinoma type I, pT1a, G3, pT1b, G1/2, systematic lymphadenectomy can be performed.

If extensive lymphatic vessel invasion (at least high-intermediate risk group) is present in endometrial carcinoma type I stage I, pT1a G1-G3, pT1b G1/G2, a systematic LNE should be performed, even if no other risk factors are present. If a negative sentinel is present, LNE can be omitted.

6.7

6.11

modified

B For endometrial carcinoma type I, pT2 to pT4, M0, G1-3, systematic lymphadenectomy should be performed if macroscopic tumor clearance can be achieved.

In endometrial carcinoma type I, pT2 to pT4, M0, G1-3, (sentinel-assisted) systematic lymphadenectomy should be performed if macroscopic tumor clearance can be achieved.

6.12

new

If bulky nodes are present in patients with endometrial cancer (all stages, all histologies), sentinel node biopsy is no longer informative.

6.9

6.13

modified

In type II endometrial carcinoma, systematic lymphadenectomy should be performed when macroscopic tumor freedom can be achieved.

In endometrial carcinoma type II, (sentinel-assisted) systematic lymphadenectomy should be performed if tumor freedom can be achieved macroscopically.

6.10

6.15

modified

If lymphatic vessel invasion is present in endometrial cancer, even in the absence of other risk factors, LNE may be performed.

For carcinosarcomas of the uterus, (sentinel-assisted) systematic LNE should be performed.

6.12

6.16

modified

Sentinel lymph node biopsy alone for endometrial cancer should be performed only in controlled trials.

The combination of systematic LNE and sentinel biopsy (that is, sentinel-assisted LNE) may improve the detection of positive lymph nodes.

6.17

new

If sentinel node biopsy is performed, it should be performed according to the following algorithm: 1. laparoscopy and visualization of the situs (adhesiolysis if necessary) 2. intracervical injection of ICG 3. post-injection of ICG, if necessary 4. If despite post-injection of ICG only unilateral visualization of a sentinel is possible, a systematic pelvic LNE should be performed on the ICG-negative side (except in pT1a/G1-2) 5. Work-up of the sentinel LK by ultrastaging (see background text for details).

6.14

6.19

modified

Robotic-assisted laparoscopic procedures can be used in the same manner as conventional laparoscopy for EC surgery.

Robotic-assisted laparoscopic procedures can be used in the same manner as conventional laparoscopy for endometrial cancer surgery. They may offer advantages in morbidly obese patients.

6.21

new

For advanced primary unresectable endometrial cancer, neoadjuvant platinum-containing chemotherapy followed by cytoreductive surgery may be considered.

7.1

new

In all stage I and II endometrial carcinomas with POLE mutation, adjuvant radiotherapy and/or chemotherapy can be omitted in R0 situation, even if risk factors are present.

7.1

7.2

modified

In stage pT1a, pNX/0, G1 or G2, endometrioid EC (type I), after hysterectomy with or without lymph node dissection, neither brachytherapy nor percutaneous irradiation should be performed.

In stage pT1a, pNX/0, G1 or G2, endometrioid endometrial carcinoma (type I), p53-wt and L1CAM negative, no extensive LVSI after hysterectomy with or without lymph node dissection, neither brachytherapy nor percutaneous irradiation should be performed.

7.2

7.4

modified

In stage pT1a, pNX/0 without involvement of the myometrium, G3, endometrioid EC (type I), vaginal brachytherapy may be performed to reduce the risk of vaginal recurrence.

In stage pT1a, pNX/0 without involvement of the myometrium, G1-3, p53-abn or L1CAM positive (each POLE wild type), endometrioid endometrial carcinoma (type I), adjuvant vaginal brachytherapy or percutaneous radiotherapy can be performed, if necessary in combination with chemotherapy.

7.3

7.5

modified

In stage pT1b, G1 or G2 pNX/0 and in stage pT1a (with myometrial involvement), G3 pNX/0, endometrioid EC (type I), vaginal brachytherapy alone should be performed postoperatively to reduce the risk of vaginal recurrence.

In stage pT1b, G1 or G2 pNX/0 and in stage pT1a (with myometrial involvement), G3 pNX/0, endometrioid endometrial carcinoma (type I), p53-wt, L1 CAM negative, no extensive LVSI, vaginal brachytherapy alone should be performed postoperatively.

7.6

new

In stage pT1b, G1-3 pNX/0 and in stage pT1a (with myometrial involvement), G1-3 pNX/0, endometrioid endometrial carcinoma (type I), p53- abn and/or L1CAM positive and/or extensive LVSI, percutaneous irradiation should be performed postoperatively.

7.7

new

Radiation should be given in combination with chemotherapy in this situation (7.6.).  See chapter System therapy.

7.8

new

Patients with endometrioid endometrial carcinoma (type I) stage pT1b pN0 G3 (without LVSI and p53-wt and L1CAM negative) should undergo vaginal brachytherapy.

7.9

new

Patients with stage pT2 pNX with additional risk factors (G3 or > 50% myometrial infiltration or LVSI) should receive percutaneous radiotherapy.

7.4

7.10

modified

Patients with stage pT1b pNX G3 or stage pT2 pNX, endometrioid EC (type I), should receive vaginal brachytherapy; alternatively, percutaneous radiotherapy may be performed.

For patients with stage pT1b pNX G3 (without LVSI, p53-wt, L1CAM negative), endometrioid endometrial cancer (type I), vaginal brachytherapy or percutaneous radiotherapy should be performed

7.4

7.11

modified

Patients with stage pT1b pNX G3 or stage pT2 pNX, endometrioid EC (type I), should receive vaginal brachytherapy; alternatively, percutaneous radiotherapy may be performed.

For patients with stage pT2 pNx, G1/G2, (less than 50% myometrial infiltration, without LVSI, p53-wt, L1CAM negative), endometrioid EC (type I), vaginal brachytherapy or percutaneous radiotherapy should be performed.

7.12

new

Patients with endometrioid endometrial carcinoma (type1) stage pT1b and pT2 p53-abn, POLE-wt should receive percutaneous radiotherapy in combination with chemotherapy (PORTEC 3 regimen).

7.13

new

For patients with stage pT2 pNX G3 or > 50% myometrial infiltration or LVSI, radiation may be given in combination with chemotherapy.

7.14

new

In patients with endometrioid endometrial carcinoma (type I) stage pT2 pN0 (without other risk factors such as G3, > 50% myometrial infiltration or LVSI and p53-wt AND L1CAM negative), endometrioid EC (type I), vaginal brachytherapy should be performed.

7.15

new

Patients with endometrioid endometrial carcinoma (type I) pT2 pN0 with risk factors (> 50% myometrial infiltration or LVSI or L1CAM positive) should undergo percutaneous pelvic radiotherapy.

7.16

modified

For patients with positive LK, involvement of the uterine serosa, adnexa, vagina, bladder, or rectum (i.e., stages III to IVA overall) with endometrioid EC (type I), postoperative external pelvic irradiation may be performed in addition to chemotherapy to improve local control.

7.17

Patients with endometrioid EC (type I) and positive LK, involvement of the uterine serosa, adnexa, vagina, bladder, or rectum (stages III-IVA) may alternatively receive adjuvant chemotherapy followed by percutaneous radiotherapy.

Patients with endometrioid endometrial carcinoma (type I) and positive LK, involvement of the uterine serosa, adnexa, vagina, bladder, or rectum (stages III-IVA) should receive adjuvant percutaneous radiotherapy followed by simultaneous chemotherapy or, alternatively, chemotherapy alone in combination with vaginal brachytherapy.

new

7.18

new

If simultaneous radiochemotherapy followed by chemotherapy is chosen, the regimen used in the PORTEC-3 trial should be applied.

7.19

new

When chemotherapy is combined with vaginal brachytherapy alone, brachytherapy may be given after or between chemotherapy administrations.

7.8

7.20

modified

In the presence of specific risk factors for vaginal recurrence (stage II or stage IIIB-vaginal, each with close or positive incision margins), additional vaginal brachytherapy may be performed as a boost after postoperative external pelvic irradiation after hysterectomy due to endometrioid EC.

In the presence of specific risk factors for vaginal recurrence (stage II or stage IIIB-vaginal or LSVI or close vaginal resection margin, additional vaginal brachytherapy may be performed as a boost after postoperative pelvic irradiation after hysterectomy due to endometrioid endometrial carcinoma.

7.9

7.21

modified

The indication for postoperative vaginal brachytherapy or external pelvic irradiation for type II carcinoma (serous or clear cell) should be based on the recommendations for type I carcinoma (endometrioid) of grade G3 of the same stage.

Patients with serous endometrial carcinoma and patients with p53-mutated endometrial carcinoma of all stages should receive vaginal brachytherapy (stage I) or adjuvant percutaneous radiotherapy (stage II and above).

7.10

7.22

modified

To improve local control, postoperative radiotherapy should be given for carcinosarcoma in the presence of stage FIGO I or II.

To improve local control, postoperative radiotherapy should be given in addition to chemotherapy for carcinosarcoma when stage FIGO I or II is present.

7.23

new

In the case of carcinosarcoma, an individualized radiation concept can be carried out if higher stages are present.

8.2

8.2

modified

Patients with endometrioid or other type I endometrial carcinoma (ICD-0: 8380/3, 8570/3, 8263/3, 8382/3, 8480/3) at stage pT1a/b G1 and G2 cN0/pN0 should not receive adjuvant chemotherapy.

Patients with primary type I endometrial carcinoma stage pT1a/b G1 and G2 cN0/ pNsn0, p53-wt, should not receive adjuvant chemotherapy.

8.3

8.3

modified

For patients with endometrioid or other type I endometrial carcinoma at stage pT1a G3 cN0 or pN0, there are insufficient data on the benefit of adjuvant chemotherapy.

For patients with endometrioid or other type I endometrial carcinoma at stage pT1a G3 cN0 or pN0, p53-wt, there are insufficient data on the benefit of adjuvant chemotherapy.

8.4

8.4

modified

Adjuvant chemotherapy can be given to patients with type II endometrial carcinoma and to patients with type I endometrial carcinoma G3 pT1b and stage pT2 (both pN0).

For patients with type I endometrial carcinoma G3 pT1b, without POLE mutation or stage pT2 (each pN0), adjuvant chemotherapy with 3 or 6 cycles (see Statement 8.13) may be considered as an adjunct to vaginal brachytherapy (see Radiation Therapy recommendation) or percutaneous radiotherapy alone without chemotherapy.

8.5

new

Patients with type I endometrial carcinoma G3 pT1b or stage pT2 (both pN0) with POLE mutation should not receive adjuvant chemotherapy.

8.6

new

In patients with serous endometrial carcinoma in FIGO stage I - III, adjuvant therapy should be performed according to the PORTEC III regimen (= radiochemotherapy followed by chemotherapy). For stage III serous endometrial carcinoma, adjuvant chemotherapy alone may be given as an alternative (carboplatin AUC 6 / paclitaxel 175 mg/m2).

8.7

new

Patients with type 1 endometrial carcinoma and abnormal p53 status on immunohistochemistry (type I endometrial carcinoma stage 1a or higher, with infiltration into the myometrium, or clear cell endometrial carcinoma) should be treated as patients with serous endometrial carcinoma.

8.5

8.8

new

Patients with stage pT3 and/or pN1 endometrial cancer should receive adjuvant chemotherapy.

Patients with stage pT3 and/or pN1 endometrial cancer should receive adjuvant chemotherapy or adjuvant therapy according to the PORTEC-3 regimen.

8.6

8.9

new

Patients with stage pT4a or M1 endometrial cancer who have undergone macroscopic tumor-free surgery or have a maximum postoperative residual tumor less than 2 cm should receive chemotherapy.

Patients with stage pT4a or M1 endometrial cancer who have undergone macroscopic tumor-free surgery or have a maximum postoperative residual tumor less than 2 cm should receive adjuvant chemotherapy, possibly in combination with radiotherapy.

8.7

8.10

modified

Adjuvant chemotherapy for endometrial cancer should be performed with carboplatin and paclitaxel.

8.11

If chemotherapy alone is contraindicated to paclitaxel or carboplatin, adriamycin and cisplatin may also be used.

Adjuvant chemotherapy for endometrial cancer should be given with carboplatin AUC 6 and paclitaxel 175 mg per square meter. After percutaneous radiotherapy, carboplatin AUC 5 should be dosed.

modified

8.8

8.12

modified

Patients with carcinosarcoma FIGO stage I or II may receive adjuvant chemotherapy with cisplatin/ifosfamide at a dose of ifosfamide 1.6 g/m2 i. v. day 1-4 and cisplatin 20 mg/m2 i. v. day 1-4 or carboplatin/paclitaxel at a dose of paclitaxel 175 mg/m2 day 1 and carboplatin AUC 5.

Patients with carcinosarcoma FIGO stage I or II may receive adjuvant chemotherapy with carboplatin/paclitaxel (at a dosage of paclitaxel 175 mg/m² day 1 carboplatin AUC 6 day 1) or cisplatin/ifosfamide (at a dosage of ifosfamide 1.6 g/m² day 1-4 and cisplatin 20 mg/m² day 1-4).

8.10

8.14

modified

Given the high toxicity of ifosfamide-containing combinations, the combination of carboplatin and paclitaxel may also be used as adjuvant chemotherapy in patients with carcinosarcoma.

Given the high toxicity of ifosfamide-containing combinations, the combination of carboplatin and paclitaxel can also be used as adjuvant chemotherapy in patients with stage FIGO III or IV carcinosarcoma at a dosage of paclitaxel 175 mg/m2 day 1 and carboplatin AUC 6 or cisplatin/ifosfamide at a dosage of ifosfamide 1.6 g/m2 i. v. day 1-4 and cisplatin 20 mg/m2i. v. day 1-4.  

9.14

9.14

modified

Endocrine therapy with MPA (200 mg/d) or MGA (160 mg/d) can be given to women with recurrence after EC.

Endocrine therapy with MPA (200-250 mg/d) or MGA (160 mg/d) or tamoxifen (20 mg/d or 40 mg/d) or a combination of tamoxifen and MPA/MGA can be given to women with recurrence after endometrial cancer.

9.15

9.15

modified

In women with recurrence after EC, endocrine therapy with MPA results in higher response rates when progesterone receptor expression or estrogen receptor expression or good-to-moderate tumor differentiation (G1/G2) is detectable.

In women with recurrence after endometrial cancer, endocrine therapy with MPA or tamoxifen results in higher response rates when progesterone receptor expression or estrogen receptor expression or good-to-moderate tumor differentiation (G1/G2) is detectable.

9.16

9.16

modified

Systemic chemotherapy may be given to women with EC recurrence that cannot be treated locally or distant metastasis.

Chemotherapy may be given to women with EC recurrence that cannot be treated locally or distant metastasis.

9.17

9.17

modified

The superiority of a particular chemotherapy regimen in women with recurrence after EC has not been established. Platinum salts, anthracyclines, and taxanes are considered the most effective agents for chemotherapeutic therapy of advanced or recurrent EC. The combination of carboplatin with paclitaxel has been established as a relatively well-tolerated and safe therapy.

The superiority of a particular chemotherapy regimen in women with recurrence after endometrial carcinoma has not been established. The carboplatin/paclitaxel and doxorubicin/cisplatin/paclitaxel combinations have been shown to be equieffective agents for chemotherapeutic therapy of advanced or recurrent endometrial carcinoma. Because of better tolerability, carboplatin (AUC 6) should be used with paclitaxel (175 mg/m2).

9.18

new

Patients with locally advanced or recurrent serous endometrial carcinoma with her2/neu overexpression may receive systemic chemotherapy with carboplatin (AUC 5) and paclitaxel (175 mg/m2) combined with trastuzumab (8 mg/kg as initial dose, followed by 6 mg/kg as maintenance therapy).

9.19

new

Patients with recurrent or primary advanced endometrial cancer with microsatellite-stable/mismatch-repair functional tumor tissue and progression after at least one line of chemotherapy should receive combined immune and multikinase inhibitor therapy with pembrolizumab (200 mg i.v. d1, q21 or 400 mg i.v. d1, q42) and lenvatinib (20 mg p.o. 1 x daily). The high toxicity should be noted.

9.20

new

In patients with recurrent or primary advanced endometrial cancer with microsatellite unstable/mismatch-repair deficient tumor tissue (MSI-H or MMRd), immunotherapy with dostarlimab (4 cycles 500mg i.v. d1, q3w followed by 1000mg i.v. d1, q6w) or with pembrolizumab (200 mg i.v. d1, q21 or 400 mg i.v. d1, q42).

10.3

10.3

modified

If a hereditary form of endometrial cancer is suspected, the patient should present to a certified gynecologic cancer center.

If a hereditary form of endometrial cancer is suspected, the patient should present to a certified gynecologic cancer center or a center for hereditary tumor diseases.

10.4

10.4

modified

Already ill persons, carriers and persons at risk for monogenic hereditary diseases with increased risk for endometrial carcinoma and other malignancies should be informed about the possibility and benefit of psychosocial counseling and care.

People who already have the disease, carriers of the disease and people who have not yet been tested (persons at risk) from families with a hereditary tumor syndrome should be made aware of the possibility and benefit of psychosocial counseling and care.

10.6

10.6

modified

A (molecular) pathological examination with regard to Lynch syndrome in tumor tissue should be performed in case of endometrial carcinoma diagnosed before the age of 60.

If a suspicious finding is raised during routine testing for MMR deficiency (immunohistochemical testing of MMR genes or microsatellite analysis), education and, if necessary, counseling under the Genetic Diagnostics Act should be offered regarding diagnostic genetic testing for Lynch syndrome.

10.7

10.7

modified

In patients from families in which the Amsterdam criteria are fulfilled and whose tumor tissue does not show Lynch syndrome-typical abnormalities, Lynch syndrome cannot be excluded.     Therefore, genetic counseling should be performed for assessment and, if necessary, further diagnosis.

In patients from families in which the Amsterdam criteria are fulfilled and whose tumor tissue does not show Lynch syndrome-typical abnormalities, Lynch syndrome cannot be excluded.   Therefore, for assessment and, if necessary, further diagnostics, education and, if necessary, genetic counseling for diagnostic genetic testing should be offered in a center for familial tumor diseases with appropriate expertise.

10.8

10.8

modified

If Lynch syndrome is suspected based on an abnormal molecular pathology finding, the affected individual should be offered a germline mutation search in the likely affected MMR gene(s).

If there is evidence of MMR deficiency and suspicion of Lynch syndrome based on abnormal immunohistochemistry or molecular pathology (failure of MMR proteins) or high microsatellite instability (MSI-H), the affected individual should be offered education and, if appropriate, genetic counseling for germline mutation analysis in the likely affected MMR gene(s).

10.13

10.10

modified

Once the causative mutation is known to run in the family, the patient should be advised to inform family members who may be affected of the increased risk.

Once the causative mutation is known in the family, the patient should be advised to inform family members of the increased risk and the options for genetic counseling and (predictive) genetic testing.

11.9

11.8

modified

The communication of information and education of the patient should take place early and according to the basic principles of patient-centered communication, which enables participatory decision-making.

The communication of information and education of the patient should take place at an early stage and according to the basic principles of patient-centered communication, which enables participatory decision-making. This should include the following aspects:  * expression of empathy and active listening, * direct and empathetic addressing of difficult issues, * avoidance of medical terminology, explanation of technical terms when appropriate, * strategies to improve understanding (repetition, summary of important information, use of graphics, etc.), * encouragement to ask questions, * permission and encouragement to express feelings, * offering further help.

11.9

new

To improve patient education, physicians should complete quality-assured training on communication with patients.

11.12

11.12

modified

All patients should be offered palliative care after diagnosis of a non-curable cancer, regardless of whether tumor-specific therapy is used.

All patients should be offered palliative care (APV or SPV) after diagnosis of noncurable endometrial cancer, regardless of whether tumor-specific therapy is used.

11.13

new

For patients with noncurable endometrial cancer, the complexity of the palliative situation should be repeatedly assessed; this includes: the patient and family needs, the patient's functional status, and the disease phase.

11.12.2

deleted

Specialized palliative care should be integrated into oncology decision-making processes, e.g., through participation in interdisciplinary tumor conferences.

11.12.3

11.14

modified

Patients with a non-curable cancer and a high complexity of their situation should receive specialized palliative care.

Patients with noncurable endometrial cancer and high complexity of their situation should receive specialized palliative care.  S3 Guideline Palliative Care.<https://www.leitlinienprogramm-onkologie.de/leitlinien/palliativmedizin/>

11.17

new

Endometrial cancer patients should be informed about tumor-associated fatigue and screened systematically and repeatedly during the different treatment phases. Screening according to NCCN is recommended.

11.18

new

If there is a value > 3 in the screening, a diagnostic assessment should be performed for further clarification and specific counseling on fatiguemanagement and treatment if needed.

11.19

new

For moderate or severe fatigue, moderate strength and endurance training should be provided based on physical performance level

11.20

new

Psychoeducation or cognitive behavioral therapy should be offered for moderate or severe fatigue

11.21

new

For moderate or severe fatigue, mindfulness-based stress reduction (MBSR) and yoga may be offered.

11.22

new

Yoga should be recommended to reduce fatigue in these patients.

12.1

new

Treatment decisions for older patients should be based on current standard recommendations and modified by general status, life expectancy, patient preference, and an individual benefit-risk assessment.

12.2

new

Determination of general status in patients older than 75 years should be determined by geriatric assessment or by a screening/geriatric assessment algorithm especially if surgery with general anesthesia or chemotherapy is planned to minimize complications as well as improve treatment adherence, chemotherapy tolerance, and possibly survival.

12.3

new

The sole consideration of calendrical age does not do justice to the complexity and multi-layered nature of the general status. Rather, geriatric assessment and management should include therapy-relevant geriatric domains (especially functionality-associated parameters such as activities of daily living, mobility, cognition, falls, and morbidity-associated parameters such as multimedication, nutrition, fatigue, and number of comorbidities) to adjust therapy selection accordingly and initiate supportive measures.