Endometrial Cancer

 Introduction and Epidemiology

Endometrial cancer is a common gynecological malignancy.

Epidemiology.

Prevalence in Kenya is unknown but hospital based data show that for every 30 cases of cervical cancer, there is one case of endometrial cancer.

 Lifetime risk of developing endometrial cancer is approximately 2%.

In USA, it causes approximately 6000 deaths.

About half of patients with endometrial cancer have risk factors for the disease, including;

  •  obesity
  •  unopposed estrogen exposure (exogenous or endogenous e.g. estrogen secreting ovarian tumours such as granulosa and theca cell tumors,
  • older age
  • chronic anovulation;
  • low parity/nulliparity
  • early menarche (onset below 12 years)
  • late menopause (above 52 years)
  • use of tamoxifen
  • diabetes mellitus
  • and history of breast or ovarian cancer.
     

 Diagnosis

Abnormal vaginal bleeding including postmenopausal bleeding/spotting occurs in 90% of patients.

Though most patients are postmenopausal, about a quarter of them are premenopausal with 5% below 40 years of age.

Majority of young patients are obese or have high levels of unopposed endogenous estrogen from chronic anovulation or from polycystic ovary disease.

Initial evaluation should include full physical examination, (pelvic examination noting the size, position and contour of the uterus).

Screening for cervical cancer should be performed.

Diagnosis requires histopathological evaluation of endometrial tissue.

One should consider primary endocervical adenocarcinoma or extension of cervical carcinoma into the endometrium.

Therefore, both endocervical and endometrial sampling should be performed.

Devices for use in the offi allow endometrial sampling and accurate diagnosis.

Hysteroscopic evaluation and biopsy may be performed where facilities are available.

Pelvic ultrasonography may be suggestive of disease. More than 90% of all cancers are endometroid in type.

Other types are serous, clear cell, mucinous, mixed cell, transitional cell and sarcomas.
 

Staging and risk assessment

Degree of Differentiation

Histological diffrentiation is important in determining treatment and prognosis.

Response to treatment decreases with increasing grade. WHO grading (grade 1: nonsquamous, non-morula solid growth pattern in ≤5% of tumour; grade 2: non-squamous, non-morula solid growth pattern in 5-50% of tumour; grade 3: non-squamous, non morula solid growth pattern in >50% of tumour).

Pre-operative Evaluation and Preparation.

• Laboratory investigations: total blood count, renal function tests, liver function    tests, blood sugar, others as necessary.

• Imaging: chest X-ray, pelvic ultrasonography (transvaginal), pelvic and abdominal CT scan, MRI scan (contrast-enhanced dynamic MRI) for uterine and pelvic spread
   

The most popular staging classifiation for endometrial cancer is the FIGO system. This is a surgical staging system.

FIGO Staging for Endometrial Carcinoma

STAGE DESCRIPTION


Stage
I


Confied to the uterus
IA: Confied to the endometrium
IB: Invasion to <50% myometrium
IC: Invasion to >50% myometrium

 

Stage
II

Extension to uterine cervix
IIA: Endocervical glandular involvement only
IIB: Cervical stromal invasion

 

Stage
III

Extension beyond the uterus
IIIA: Tumour invades serosa and/or adnexa positive
peritoneal cytology
IIIB: Vaginal involvement
IIIC: Metastasis to pelvic or para-aortic lymph nodes

 

Stage
IV

Spread to neighbouring organs or distant metastasis
IVA: Invasion to bladder and/or bowel mucosa
IVB: Distant metastasis including intraabdominal or
   inguinal lymph nodes

 

Prognostic Factors

  •  Surgical stage
  •  Histological grade
  •  Depth of myometrial invasion
  •  Histological type
  •  Tumour diameter
  •  Invasion of lymphovascular space
  •  Age of patient
  •  Endocervical stromal invasion
     
Risk Categorization for Endometrial Carcinoma

Low risk:
 

Stage IA/IB, grade 1 or 2, endometrioid histopathological type
 

Intermediate risk:

Stage IC, grade 1 or 2, endometrioid histopathological type
 

Stage IA/IB, grade 3, endometrioid histopathological type
 

High risk:

Stage IC, grade 3, endometrioid histopathological type
 

Stage IA/IB/IC, serous, clear cell, small cell or
undiffrentiated histopathological type

 

 Management

Surgery is the main stay of treatment.

This involves total abdominal hysterectomy (TAH) and bilateral salpingoopherctomy (BSO).

Chemotherapeutic regimens containing doxorubicin, cis-platin, carboplatin, paclitaxel, docetaxel, topotecan, ifosfamide, 5-florouracil, methotrexate.

These are usually administered in various combinations but single agents can also be administered.

High dose medroxyprogesterone acetate may also be included in steroid-receptor positive cases.
 

Pharmacological management

Cisplatin, carboplatin, paclitaxel, docetaxel, doxorubicin, topotecan, ifosfamide, vinorelbine, tamoxifen.

In resource limited settings, cisplatin with doxorubicin is the preferred treatment option.

Where resources are available taxane and a platinum compound are used.
 

Prognosis

Early stage presentation is curable with surgery alone.

 References

  1. .American Cancer Society. Cancer Facts and Figures 2009
  2. .Suh-Burgmann EJ, Goodman A. Surveillance for endometrial cancer in    women receiving tamoxifen. Ann Intern Med 1999;131:127-135.3.Randall ME, Filiaci VL, Muss H, et al.
  3. Randomized phase III trial of  whole-abdomianl irradiation versus doxorubicin and cis-platin chemotherapy in advanced endometrial carcinoma: A Gynaecologic   Oncology Group Study. J Clin Oncol 2006;24:36-44
  4. .Fleming GF, Brunetto VL, Cella D, et al. Phase III trial of doxorubicin  plus cis-platin with or without paclitaxel plus figrastim in advanced edometrial carcinoma; A Gynaecology Oncology Group Study . J Clin Oncol 2004;22:2159-2166

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