endometrial%20cancer
ENDOMETRIAL CANCER

Endometrial cancer is also known as uterine cancer, cancer of the corpus uteri, uterine corpus cancer, endometrical carcinoma.

It is the 6th most common malignancy worldwide.

Management of endometrial cancer should be divided based on risk, disease stage & patient's desire for fertility.

Principles of Therapy

  • Management of endometrial cancer should be divided based on risk, disease stage and patient's desire for fertility
  • Cytoreduction therapy, which includes debulking with surgery and chemotherapy or radiation therapy, improves survival rate and helps reduce recurrence in patients with intra-abdominal disease
  • Surgical approach should include extrafascial hysterectomy-bilateral salphingo-oophorectomy (TAH-BSO), lymphadenectomy, pelvic washing cytology

Adjuvant Therapy

  • May be considered depending on the extent, risk group and staging

Low-Risk

  • Adjuvant therapy is not recommended in patients with low-risk endometrial cancer
    • No improvement in overall survival was seen in patients given adjuvant brachytherapy or pelvic external beam radiotherapy (EBRT), and may otherwise increase morbidity and mortality risk of patients

Intermediate-Risk

  • Adjuvant vaginal brachytherapy may be considered and is optional for patients <60 years of age

High-Intermediate-Risk

  • Adjuvant vaginal brachytherapy may be considered
  • For patients who did not undergo surgical nodal staging, adjuvant EBRT is recommended
    • May consider adjuvant brachytherapy for those with grade 3 tumors but negative for lymphovascular space invasion 
  • Participation in clinical studies should be encouraged

High-Risk

  • Adjuvant EBRT with limited fields should be considered for high-risk stage I endometrial cancer patients if surgical nodal staging was performed and confirmed negative for node involvement; adjuvant brachytherapy is an alternative treatment if EBRT cannot be tolerated
  • For high-risk stage I endometrial cancer patients who did not undergo surgical nodal staging, adjuvant EBRT is recommended and sequential adjuvant chemotherapy may be considered
  • For high-risk patients with stage II endometrial cancer who underwent simple hysterectomy, surgical nodal staging and confirmed node-negative:
    • Vaginal brachytherapy is recommended
    • Limited field EBRT is recommended for grade 3 patients or those positive for lymphovascular space invasion may also consider brachytherapy and chemotherapy 
  • For high-risk patients with stage II endometrial cancer who underwent simple hysterectomy but did not undergo surgical nodal staging, EBRT is recommended, and brachytherapy is recommended
    • Sequential adjuvant chemotherapy should be considered in patients with grade 3 tumor 
  • EBRT and chemotherapy are recommended for patients with high-risk stage III endometrial cancer without residual disease
    • Combination EBRT-chemotherapy with or without vaginal brachytherapy is recommended in patients with stage IIIA, IIIB & IIIC1 FIGO classes
    • Chemotherapy & extended field EBRT with or without vaginal brachytherapy is recommended in patients with stage IIIC2 FIGO classification 
  • For patients with high-risk non-endometrioid cancer with serous & clear cell type based on staging, chemotherapy should be given
    • Vaginal brachytherapy may be considered in patients with stage IA lymphovascular space invasion-negative disease
    • Chemotherapy plus EBRT may be considered in patients with stage ≥IB, especially in patients positive for node invasion 
  • For patients with high-risk non-endometrioid cancer and undifferentiated tumors based on staging, chemotherapy is recommended, and ERBT and participation in clinical trials are encouraged

Neoadjuvant Therapy

  • May benefit patients expected to have residual disease after primary debulking surgery

Uterine Cavity-Limited Disease

  • After surgical confirmation, endometrial cancer confined within the uterine walls are best managed by surgery
  • It is recommended that surgery includes total EH-BSO and lymphadenectomy with pelvic washing cytology
  • Sentinel node mapping may also be considered

Cervical Involvement Suspected or Confirmed

  • For operable patients with cervical involvement, extrafascial hysterectomy or radical hysterectomy with bilateral salphingo-oophorectomy, pelvic washing cytology, lymphadenectomy is recommended
    • Radical or modified radical hysterectomy are options to EH-BSO
    • Adjuvant EBRT ± brachytherapy after EH-BSO is recommended 
  • For patients with uterine-confined disease with contraindications to surgery, EBRT and/or brachytherapy is preferred, and may be given with or without systemic therapy
    • Patients with endometrioid-type endometrial cancer may also be given systemic therapy (eg estrogen- and progesterone-based therapy, Tamoxifen with alternating Megestrol) 
  • For patients with gross cervical involvement with contraindications to surgery, EBRT and/or brachytherapy is preferred
    • Systemic therapy alone may also be considered, then followed by adjuvant EBRT and brachytherapy 

Suspected Extrauterine Disease

  • Neoadjuvant systemic therapy may be considered
  • Goal of surgical treatment is to eradicate all residual disease, thus debulking is recommended
  • For patients with extrauterine disease who are not candidates for surgery, EBRT with brachytherapy and systemic therapy is recommended
    • Systemic therapy alone may also be considered 
  • For patients with distant visceral metastasis, systemic therapy and EFRT and/or hormone therapy are recommended
  • Palliative EH-BSO may also be considered

Fertility-Preserving Treatments

  • Conservative treatments may also be considered for young women of childbearing age and those considering pregnancy in the future
  • Criteria for inclusion:
    • Pathologically-confirmed well-differentiated grade 1 endometrioid adenocarcinoma on dilatation and curettage
    • Disease limited to the endometrium as confirmed in MRI or transvaginal ultrasound
    • No metastasis or extrauterine involvement on imaging studies
    • No contraindications to medical therapy or pregnancy
    • Patients should have been informed that fertility-sparing therapies are not standard treatment for endometrial cancer and that close follow-up is required
  • After completion of childbearing, EH-BSO is recommended

Pharmacotherapy

Chemotherapy

  • Combination regimens are recommended for high-risk disease, recurrent or metastatic endometrial cancer
  • Single-agent therapy is used when multiagent regimens are contraindicated
  • Post-operative platinum-based chemotherapy may benefit patients with high-risk endometrioid disease (eg increased progression-free survival, overall survival

Recommended Combination Regimens

  • Carboplatin/Paclitaxel (preferred)
  • Cisplatin/Doxorubicin
  • Cisplatin/Doxorubicin/Paclitaxel
  • Cisplatin/Docetaxel
  • Ifosfamide/Paclitaxel
  • Cisplatin/Ifosfamide
  • Everolimus/Letrozole

Recommended Single-Agent IV Regimens

  • Cisplatin
  • Carboplatin
  • Doxorubicin
  • Liposomal Doxorubicin
  • Paclitaxel
  • Albumin-bound Paclitaxel
  • Topotecan
  • Docetaxel
  • New agents: Bevacizumab, Temsirolimus
    • Should be considered in patients previously given cytotoxic chemotherapeutic agents but are unresponsive to current therapy

Hormone Therapy

  • Treatment option for patients with metastatic, recurrent, or high-risk
    • May also be considered in patients with lower grade endometriod histology only with small or slow-growing tumors
  • Indicated for advanced (grade 1 or 2) endometrioid-type endometrial cancer
  • Preferred 1st-line systemic treatment for hormone-positive grade 1-2 tumors negative for rapid disease progression
  • Close monitoring with endometrial biopsy every 3-6 months is required if to undergo this management option

Recommended Hormone Therapy Regimens

  • Progestin-based agents
  • Alternating treatment with Megestrol and Tamoxifen
  • Aromatase inhibitors
  • Tamoxifen
  • Fulvestrant

Progestin-Based Therapy

  • Eg Megestrol acetate, Medroxyprogesterone acetate, intrauterine device-containing Levonorgestrel (LNG-IUD)
  • Conservative treatment in select patients with non-invasive disease, or young patients with endometrial hyperplasia, who wish to preserve their fertility
  • Contraindicated in patients at increased risk for breast cancer, stroke, myocardial infarction, pulmonary embolism, and/or deep vein thrombosis

Aromatase Inhibitors

  • Eg Anastrozole, Exemestane, Letrozole
  • May be used as alternative therapy for progestin-based agents and Tamoxifen in patients with asymptomatic or low-grade disseminated metastasis
  • Usually used in the management of breast cancer, but are being considered in endometrial cancer due to its interaction with estrogen and progesterone receptors
  • Further studies are needed to prove the efficacy and safety of aromatase inhibitors for the treatment of endometrial cancer

Tamoxifen

  • Used for metastatic or recurrent disease
  • Prevents estrogen-stimulated growth of oncologic cells

Radiotherapy

  • Radiotherapy may be considered in patients not qualified for surgery and those at moderate-high risk for recurrence

External Beam Radiotherapy (EBRT)

  • May be considered in intermediate to high-risk endometrial cancer patients with suspected or gross cervical involvement (grade 3 tumor, ≥50% myometrial invasion or cervical stroma invasion) following EH-BSO and surgical staging
    • Several studies have shown that adjuvant EBRT decreased recurrence rate and improved overall survival in patients with high-intermediate- or high-risk and those with grade 3 tumors 
  • Recommended for pelvic control in high-risk, stage I patients
  • Limited-field EBRT is recommended for patients with grade 3 tumors who are positive for lymph node involvement
  • May be considered for the palliation of symptoms in patients with painful node recurrences, bleeding, or bone metastasis

Vaginal Brachytherapy (Internal Radiation Therapy)

  • Adjuvant treatment of choice over whole pelvic radiation therapy in patients with intermediate-risk, and high-intermediate-risk patients for recurrence prevention
    • Same efficacy in patients with grade 1 or 2 tumors with 50% myometrial invasion or grade 3 tumors with <50% myometrial invasion 
  • May be considered as an alternative treatment in high-risk patients
  • Should be considered for patients after EH-BSO if with high-intermediate patients or low-risk patients but with signs of higher-risk disease
  • May provide locoregional control with competitive overall survival rates in the following patients:
    • >60 years old with intermediate to high-intermediate-risk
    • Endocervical glandular involvement present but disease confined to the uterus
    • Patients with high-intermediate-risk for recurrent endometrial cancer 
  • Should be initiated once vaginal cuff has healed, 6-8 weeks or <12 weeks post-surgery
  • Studies revealed lesser gastric toxic effects & better quality of life with vaginal compared to whole pelvic irradiation

Advanced-Stage, Metastatic, or Recurrent Endometrial Cancer

  • Radiotherapy may be considered in patients with localized vaginal relapse post-surgery
  • Chemoradiotherapy may be considered for patients with vaginal or pelvic node recurrence at high risk for systemic relapse
    • May provide the best outcome
  • Adjuvant systemic therapy or surgery prior to radiotherapy may be considered in select patients with bulky disease positive for vaginal or pelvic node recurrence
  • Repeat radiation therapy may be considered in select patients using specialized techniques
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