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.

Endometrial%20cancer Diagnosis

Classification

Types of Endometrial Cancer

Type 1 - Endometrioid (Adenocarcinoma of the Endometrium)

  • More common (80-90% of cases)
  • Grouped into 3 cases based on the degree of differentiation:
    • G1: ≤5% of a nonsquamous or nonmorular solid growth pattern; well-differentiated
    • G2: 6-50% of a nonsquamous or nonmorular solid growth pattern; moderately differentiated
    • G3: >50% of a nonsquamous or nonmorular solid growth pattern; poorly differentiated or undifferentiated 

Type 2 - Non-endometrioid

  • Serous, clear-cell, undifferentiated carcinomas, carcinosarcoma, sarcoma, malignant-mixed Mullerian tumour
  • Comprises 10-20% of incidence rate

Staging

  • Staging is based on imaging studies, histological results, and surgery
  • Determines the extent of cancer upon diagnosis
  • Important factor in the choice of treatment and can also predict prognosis

American Joint Committee on cancer (AJCC) TNM and International Federation of Gynecology and Obstetrics (FIGO) Surgical Staging Systems for Endometrial Cancer

  • Developed in 2018 by the International Federation of Gynecology and Obstetrics (FIGO) and the American Joint Committee on Cancer (AJCC)
TNM FIGO Surgical-Pathologic Findings
Primary Tumor (T)
TX - Primary tumor cannot be assessed
T0 - No evidence of primary tumor
Tis1 - Carcinoma in situ (pre-invasive carcinoma)
T1 I Tumor limited to the corpus uteri, including endocervical glandular involvement
T1a IA Tumor limited to the endometrium or occupies <½ of the myometrium
T1b IB Tumor occupies ≥½ of the myometrium
T2 II Tumor invades cervical stroma, but no extension beyond the uterus2
 T3  III Local and/or regional spread of the tumor 
T3a IIIA Tumor invades serosa of the corpus uteri and/or adnexa
T3b IIIB Vaginal involvement and/or parametrial involvement
IIIC3 Pelvic area and/or para-aortic lymph node metastasis present
 -  IV  Bladder and/or bowel mucosa tumor invasion present, and/or distant metastases 
T4 IVA Bladder and/or bowel mucosa tumor invasion present
Regional Lymph Nodes (N)4
NX Regional lymph nodes cannot be assessed
N0 Regional lymph node metastasis absent
N0(i+)1 Isolated malignant cells in regional lymph nodes ≤0.2 mm
N1 IIIC1 Pelvic lymph node metastasis present
N1mi IIIC1 Regional lymph node metastasis >0.2 mm but ≤2 mm in diameter to pelvic lymph nodes
N1a IIIC1 Regional lymph node metastasis >2 mm in diameter to pelvic lymph nodes
N2 IIIC2 Para-aortic lymph nodes metastasis present, with or without pelvic lymph node metastasis
N2mi IIIC2 Regional lymph node metastasis >0.2 mm but ≤2 mm in diameter to para-aortic lymph nodes, with or without positive pelvic lymph nodes
N2a IIIC2 Regional lymph node metastasis >2 mm in diameter to para-aortic lymph nodes, with or without positive pelvic lymph nodes
Distant Metastasis (M)
 MX  -  Distant metastasis cannot be assessed 
M0 - Distant metastasis absent
M1 IVB Distant metastasis present, including intra-abdominal, lung, liver or bone metastases and/or inguinal nodes

1No longer included in FIGO staging
2Endocervical glandular involvement only to be considered as Stage I
3IIIC1: Pelvic nodes positive for metastasis; IIIC2: Para-aortic nodes positive for metastasis with or without pelvic lymph node involvement
4Suffix (sn) added in metastasis identified only by sentinel lymph node biopsy

Evaluation

Prognostic Groups

  • Developed by the American Joint Committee on Cancer (AJCC) in 2017
Stage T N M
I T1 N0 M0
 IA T1a  N0 M0 
 IB T1b  N0 M0 
 II T2  N0  M0 
 IIIA T3a N0 M0 
 IIIB T3b N0 M0 
 IIIC T1-3 N1 M0 
 IVA T4 Any N M0 
 IVB  Any T Any N M1 

Risk Groups

  • Defined based on International Federation of Gynecology and Obstetrics (FIGO) staging and used as a guide for decision to prescribe adjuvant therapy
Risk Group Description
Low Stage I endometrioid, grade 1-2, <50% myometrial invasion, negative lymph node involvement
Intermediate Stage I endometrioid, grade 1-2, ≥50% myometrial invasion, negative lymph node involvement
High-Intermediate Stage I endometrioid, grade 3, <50% myometrial invasion, regardless of lymph node involvement or Stage I endometrioid, grade 1-2, positive lymph node involvement, regardless of depth of invasion
High Stage I endometrioid, grade 3, ≥50% myometrial invasion, regardless of lymph node involvement
Cervical stromal involvement (Stage II)
Non-endometrioid histology
Advanced Stage III residual disease and Stage IVA
Metastatic Stage IVB

History

Signs and Symptoms
  • Vaginal bleeding (90%)
  • Abdominal symptoms: Pain, bloatedness, distention, change in bowel function
  • Pelvic pain
  • Early satiety
  • Change in bladder function

Physical Examination

  • Pelvic exam and full body examination should be performed
  • Palpate the uterus and adnexa for unusual masses

Laboratory Tests

Tumor Markers

  • Eg CA-125, carcinoembryonic antigen (CEA), vimentin, estrogen receptor (ER), progesterone receptor (PgR), p16 by immunohistochemistry
  • CA-125 may be used to assess therapeutic response, but false positive results in the presence of peritoneal inflammation, radiation injury, and normal levels in vaginal metastasis render this test unreliable
  • Hormone receptor status (eg PgR, ER) may help with treatment decision-making especially if considering initiation of hormone therapy

Histopathology

Endometrial Biopsy

  • Gold standard in evaluating endometrial neoplasia
  • Used as an initial diagnostic study and to help in determination of appropriate management strategy
  • Recommended for patients with ovarian cancer undergoing fertility-sparing treatment

Lymph Node Biopsy

  • Not routinely used but may be useful in disease staging

Others

  • Pregnancy test should be conducted in all patients of childbearing age
  • CBC and prothrombin time should be done in patients experiencing heavy vaginal bleeding
  • A PAP smear may be considered to rule out other abnormal histologies

Imaging

  • Initial studies depend on symptomatology and risk for metastatic disease
  • Highly recommended for patients suspected of extrauterine disease

Magnetic Resonance Imaging (MRI)

  • Contrast-enhanced pelvic MRI is used to establish the origin and extent of the tumor, and to evaluate for myometrial invasion and cervical involvement
  • Sensitivity for myometrial invasion: 80-90%; for cervical invasion: 57-100%
  • Best radiologic modality compared to CT scan or PET scan for detection of lymph node metastases
  • Preferred imaging modality in patients who wish to preserve their fertility

Pelvic Ultrasound

  • 1st-line imaging study used to evaluate the etiology of vaginal bleeding in women suspected to have endometrial cancer or hyperplasia
  • Imaging study option if MRI is contraindicated in patients still desiring pregnancy
  • Pelvic transvaginal ultrasound (TVUS) is preferred in evaluating myoinvasion and disease extent

Hysteroscopy

  • Used to evaluate the endometrial lining for lesions causing vaginal bleeding
  • This procedure is often done together with dilation and curettage (D and C) or for biopsy

Positron Emission Tomography (PET) Scan

  • Confirmatory test in patients suspected of metastatic disease

Sentinel Lymph Node (SLN) Mapping

  • A strategy in staging endometrial cancer, used to help detect lymph node metastasis and with promising potential as an alternative to complete lymphadenectomy
  • SLN mapping with ultrastaging is preferred instead of lymphadenectomy in a patient with uterine-confined malignancy that is negative for metastasis in imaging studies or during exploration but may need further assessment for pelvic lymph node involvement, especially those with low- to intermediate-risk for metastases and those intolerant of standard lymphadenectomy
  • Involves injection of a dye (ie indocyanine green, Tc-99 radiocolloid) into the cervix, which travels to the sentinel nodes
  • Contraindicated in patients with uterine sarcoma

Chest Radiography

  • Should be performed in all patients as part of the initial assessment
  • Prompts the need for chest CT scan if with positive findings

Computed Tomography (CT) Scan

  • May be used to confirm the presence of metastasis especially if with positive findings in chest xray

Advanced-Stage, Metastatic, or Recurrent Endometrial Cancer

  • Diagnostic tests to consider:
    • Whole body PET/CT if considering surgery or locoregional therapy
    • Abdominal/pelvic/chest CT scan depending on patient’s symptoms and physical exam evaluation
    • Pelvic MRI may be considered in patients who refused to undergo hysterectomy

Screening

  • Not routinely recommended unless in symptomatic women and those at increased risk for endometrial cancer
    • Annual screening of high-risk women may be considered
    • For patients with Lynch syndrome, the following are recommended:
      • Annual screening (with gynecological exam, transvaginal ultrasound, aspiration biopsy) for individuals ≥35 years old
      • Local progesterone therapy via Levonorgestrel intrauterine device
      • Premalignant tumors should be treated
      • Prophylactic option eg total hysterectomy-bilateral salphingo-oophorectomy (TH-BSO) should be discussed
  • Women of menopausal age should be advised to report any history of vaginal bleeding or spotting
  • Biopsy and transvaginal ultrasound are used for screening
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