Cancer of the Uterus - Treatment

Contents

Treatment Types

Surgery

Surgical removal of all macroscopic tumour is the primary aim in the treatment of endometrial cancer. This can be achieved by an abdominal total hysterectomy. A bilateral salpingo-oophorectomy (TAH/BSO; removal of both ovaries and fallopian tubes) is performed because the ovaries and fallopian tubes are a preferred site for tumour spread. A pelvic lymphadenectomy can be omitted in patients with well differentiated tumours invading less than half of the myometrium as well as in patients with moderately differentiated tumours not invading the myometrium. The risk of lymph node involvement is less than 1 per cent in these patients. All other patients should undergo a bilateral pelvic lymphadenectomy. The risk of developing lymphoedema due to lymphadenectomy depends on the extent of the lymphadenectomy and ranges from 10 to 20 per cent.

Radiotherapy

Endometrial cancer is generally considered radiosensitive. Therefore radiotherapy has a role as adjunct therapy, as a treatment option for recurrent disease and for palliation. To prevent local recurrence, radiotherapy is usually applied in the form of vaginal cylinders (vaginal vault brachytherapy) with or without external beam radiation to the pelvis. Morbidity due to vaginal vault brachytherapy is usually very low and includes vaginal stenosis and dyspareunia due to shrinkage of the vagina. Radiotherapy given to the pelvis is associated with an increase risk of side effects to the bladder and rectum (sterile cystitis, proctisis) and sometimes to the intestine (diarrhoea, cramps). Severe side effects are very rare and can be treated with diet or with bowel resection.

Hormone Therapy

Endometrial cancer cells frequently express hormone receptors and are thus considered hormone receptor-positive. A clinical response to progestins can be expected only if hormone receptors are expressed on the cancer cells. The risk of thromboembolic complications due to progestin therapy is slightly increased. At present, there is no role for adjuvant therapy with progestins when a patient is considered tumour free after surgery. Progestins are mainly used in the palliative setting, in which a cure cannot be achieved. However, in 20 per cent of these patients a temporary response to treatment, and consequently a better quality of life, can be achieved.

Chemotherapy

No form of chemotherapy has been shown to be effective in the adjuvant (post-operative) setting. Chemotherapy (Adriamycin, cisPlatin, Paclitaxel) may be considered for palliation or in patients with uterine serous-papilary carcinoma (UPSC).

Endometrial Hyperplasia

Endometrial hyperplasia (EH) is a pre-malignant condition only if cytologic atypia is present (complex hyperplasia with cytologic atypia). EH with cytologic atypia usually does not respond to progestins and therefore a standard hysterectomy should be performed. EH without cytologic atypia usually responds to progestins and does not progress to invasive cancer.

Stage I Endometrial Cancer (or occult stage II)

Since the surgical removal of all macroscopic tumour is of major prognostic importance, an extrafascial total hysterectomy and a bilateral salpingo-oophorectomy is considered the standard treatment for early stage endometrial cancer. Peritoneal washings should be taken for staging reasons. Usually, the uterus is sent for frozen section examination. The decision to perform a bilateral pelvic lymphadenectomy is based on this result. In patients with well differentiated tumours invading none or less than half of the myometrium, a pelvic lymphadenectomy can be omitted. The risk of lymph node involvement is less than 1 per cent in these patients. All other patients should undergo a bilateral pelvic lymphadenectomy if there is invasion of the myoemtrium.

Clinical Stage II Endometrial Cancer

Since the surgical removal of all macroscopic tumour is of major prognostic importance, a modified radical hysterectomy (which takes the uterus and tissue from beside the cervix) and a bilateral salpingo-oophorectomy with bilateral pelvic lymphadenectomy and post-operative radiotherapy (vaginal vault brachytherapy ± external beam radiotherapy) is recommended by most authors.

For medical reasons, some patients are considered not fit for advanced surgery because the surgical and anaesthetic risks are too great. Primary radiotherapy can be offered to these patients and achieves acceptable local control with minimal risks. However, this treatment is not the standard for Stage II endometrial cancer because:

Clinical Stage III Endometrial Cancer

Surgical removal of all macroscopic tumour is of major prognostic importance. Post-operative radiation therapy will be recommended by most authors. If biopsy at laparotomy reveals endometrial cancer and a surgical removal of all macroscopic tumour seems impossible, primary radiotherapy (external beam and brachytherapy) and/or therapy with progestins may be considered.

Stage IV Endometrial Cancer

Therapy should mainly consider local control (e.g. bleeding) in the pelvis. Only limited data address the value of systemic treatment. Chemotherapy has a role in the palliative setting in order to treat cancer-related symptoms, but a cure for the cancer cannot be achieved. Local control (bleeding) might be achieved by surgery and/or radiation therapy and/or progestins.

Recurrent Disease

Three quarters of all recurrences are detected in the first three years after diagnosis. One third of these patients are free of symptoms when their recurrence is diagnosed. Most recurrences occur in the vagina and may be suitable for surgery with post-operative radiotherapy. If the recurrence is only one metastasis in the vagina, a cure from the cancer may be achieved. Patients with distant metastases might benefit from hormonal treatment (progestin) rather than from chemotherapy, as only one third of all patients show a response to chemotherapy.

Familial Risk

With rare exceptions, endometrial cancer is not hereditary. The only genetic syndrome associated with endometrial cancer is the Lynch II syndrome and involves a strong family history of adenocarcinoma in the colon, the ovaries, the female breast and the uterus. A geneticist should evaluate a careful family pedigree including the last three generations. In patients with proven Lynch II syndrome periodic mammography screening, colonoscopies and endometrial samples should be performed.

Hormone Replacement Therapy After Primary Treatment

In the past it has been argued that hormone replacement therapy might increase the risk of recurrence, as endometrial cancer cells often demonstrate hormone receptors. In contrast, retrospective analysis demonstrated that endometrial cancer patients who had HRT had a higher quality of life, had fewer recurrences and lived significantly longer than those who did not. Unfortunately, no good quality prospective data are available to confirm this. Patients with Stage I disease have such a good prognosis that the risk of osteoporosis and cardiovascular disease might exceed the risk of recurrence. Therefore, HRT is recommended by several authors for endometrial cancer patients.

Dr Andreas Obermair, MD
Associate Professor of Gynecology and Obstetrics,
University of Vienna
Clinical Fellow, Gynaecologic Oncology,Queensland Centre for Gynaecological Cancer.

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