Endometrial Cancer (Malignant Diseases of the Uterus)

Endometrial Cancer (Malignant Diseases of the Uterus)

Endometrial Cancer

(Malignant Diseases of the Uterus)

Endometrial cancer is a malignant disease of the uterus accounting for 30% of all of all other gynecological malignancies. For its quick understanding, we also have to keep in mind the anatomy of the uterus and endometrium especially.

Background

Uterus is the structure of female anatomy present in the pelvic girdle. It consists of three separate layers i-e endometrium, myometrium and perimetrium from inside to outside respectively. Malignant diseases of the uterus can present in any of these layer but endometrium is the most commonly effected layer.
Endometrium is the inner most glandular epithelial lining of the uterus so the malignancy arising from it mostly presents in abnormal glandular pattern so termed as adenocarcinoma (adeno means glandular, carcinoma means malignancy).
Adenocarcinoma of endometrium is of two type i-e endometrioid adenocarcinoma (type 1) and serous papillary carcinoma (type 2). Clinically these are entirely two different entities. Let’s clear our vision.

Differences Endometrioid Adenocarcinoma Serous Papillary Carcinoma
Incidence 90 % 10 %
Age of involvement Younger females Elderly females
Estrogen dependency Dependent Independent
Prognosis Good prognosis Poor prognosis

Rarely endometrial malignancy can present in fashion other than abnormal glandular pattern (adenocarcinoma) so must be kept in mind during evaluation. Like clear cell carcinoma also arise from endometrium.

Rarely endometrial malignancy can present in fashion other than abnormal glandular pattern (adenocarcinoma).

Incidence

Endometrial cancers cover 30% of all gynecological malignancies. These cancers can be found throughout the reproductive life of women but most cases are reported around 54 years of age (after menopause & average age of menopause is > 52 years). 25 percent of the cases occur before menopause. Lifetime risk of developing endometrial cancer is one in 90. Age related incidence is 95 per 100,000.

Aetiology

As for aetiology, no pin point cause is identified yet but there is confirmed association of high circulating estrogen level with endometrial cancer. The proof comes by the fact, oral contraceptive pill (OCP) and progesterone only pill reduce the incidence up to 50%. More of that, smoking also decreases the risk of endometrial cancer possibly by tobacco’s anti-estrogenic effects. So any factor leading to high circulating estrogen level may be responsible for endometrial caner. Certain risk factor are;

Risk Factor Possible Explanation
Obesity Androgens are converted to estrogen in peripheral adipose tissue
Diabetes/p> Insulin & insulin like growth factor in diabetics stimulate estrogen interaction
Nulliparous Estrogen remains unopposed and elevated throughout the reproductive age just due to lack of pregnancy
Late menopause For more life span, endometrium is exposed to estrogen
Unopposed estrogen therapy (You are welcome to explain here)
Tamoxifen Therapy As selective estrogen receptor modulator (SERM), prevents breast cancer by selectively blocking estrogen receptors in breast but increases its circulating level on other side and increases risk by factor of 2.5
Hormone replacement therapy (HRT) (You are welcome to explain here)
Family history of colorectal or ovarian cancer (You are welcome to explain here)

Clinical Presentation

Clinically two types of patients you may confront either post-menopausal or pre-menopausal ones. So clinical presentation for both of them should be in mind. The classical and common symptom for both is abnormal vaginal bleeding (in 90% of cases).
Pre-menopausal women commonly present with inter-menstrual bleeding (IMB), blood stained vaginal discharge, heavy menstrual bleeding (HMB), lower abdominal pain or dyspareunia.
Post-menopausal women with vaginal bleeding should be investigated for malignancy as incidence of gynecological malignancies is 10% in post-menopausal women.

Abnormal vaginal bleeding is the classic and common symptom both for pre-menopausal and post-menopausal women.

10% of the cases have unusual presentation and are more prone to be misdiagnosed and advance to complications. In advanced cancer, fistula formation, bony metastases, altered liver functions and respiratory symptoms may be evident.
Abnormal glandular cytology found at the time of cervical smear merit further investigations which may reveal endometrial cancer but such a case is very rare.

Diagnosis

Cancers are finally diagnosed by the histological examination of the biopsy samples but what triggers to take biopsy in such patients is the question. The array should be such, the patient comes to you with abnormal vaginal bleeding and you would start with proper history and examination.
Then speculum examination reveals the blood arising from the cervix. Now you perform the bimanual examination of the uterus which shows its enlargement. It is the time to seek help from investigations to confirm your findings, the mainstays of which are ultrasound scanning, hysteroscopy and endometrial biopsy.
Transvaginal ultrasound scans (TVS) tells quick and accurate assessment of endometrial thickness. Cancer is very unlikely to be present if endometrium is less than 4 mm thickened. If measurements are more than 4 mm, we have to perform hysteroscopy (usually done in general anaesthesia) which allow direct visualization of the endometrium. We can pick biopsy sample during hysteroscopy directly with the help of Pipelle or curettage.
Now the histological report confirms whether the uterus is malignant or not? It tells us clearly about the grade and stage of the tumor so we manage it accordingly.
Following a diagnosis of endometrial cancer, MRI is performed to declare extent of disease (stage) and its involvement of the structures surrounding the uterus.

Staging & Management

FIGO classification is a surgical classification to stage the endometrial cancer.

<td “> 4

Stage Explanation
1 Confined to uterine body
1a Less than 50% invasion
1b More than 50% invasion
2 Tumor invading cervical stroma
3 Local and / regional spread of tumor
3a Invades serosa of uterus
3b Invades vagina and / parametrium
3c Metastases to pelvic and / para-aortic nodes
4 Tumor invades bladder +/- bowel +/- distant metastases

Management of endometrial cancer depends upon the stage at at the time of presentation. Surgery is the most common treatment for endometrial cancer in most instances.

Surgery

Majority of the patients present with stage 1 disease so surgery is the most acceptable treatment for such scenarios. The extent of surgery will depend upon a number of factors including grade of disease, MRI stage and patient’s co-morbidities.
The standard surgery is total hysterectomy & bilateral salpingectomy. These procedures can be performed abdominally or laparoscopically (total, vaginally or robotically). If patient is low grade (grade 1-2) or MRI suggests disease less than stage 1B, this surgery is adequate. If MRI suggests cervical involvement, a radical hysterectomy with pelvic node dissection can be performed. If the tumor is high grade (grade 3) or papillary serous, many centres will perform pelvic and para-aortic node dissection as the risk of nodal disease (to pelvic or para-aortic chain) can be as high as 30%.

Adjuvant Treatment

Postoperative radiotherapy reduces the local recurrence rate but it does not influence survival rate. Different strategies for treatment for treatment include local radiotherapy to vaginal vault given over a short period of time (high dose radiotherapy, HDR), external beam radiotherapy given for locally advanced disease (stage 3) in combination with HDR. Chemotherapy is also useful for metastatic disease to combat the risk of distant spread of the cancer.

Prognosis

Five-year survival rate for endometrial cancer is 80% but considerable variation is there depending upon tumor type, stage and grade of tumor.

Stage 5-Year Survival rate (%)
1 88 (66-93)
2 75
3 55
4 16

Adverse prognostic features for survival include advanced age (more than 70 years), high BMI, grade 3 tumors, papillary serous or clear cell histology, lymphovascular space involvement, nodal metastases and distant metastases.

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Endometrial Cancer (Malignant Diseases of the Uterus)

Endometrial Cancer (Malignant Diseases of the Uterus)

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