Fertility sparing treatment for endometrial cancer

Endometrial (uterine) cancer develops when cells grow and multiply abnormally in the endometrium, the inner lining of the uterus. Endometrial cancer is the most common gynaecological cancer and is diagnosed in approximately 3,000 women in Australia each year. Of these, about 10% of women who are diagnosed are under 40 years of age.

The standard treatment for endometrial cancer is surgery to remove the uterus, which is called hysterectomy; which always results in infertility. While fertility is not a big issue for some women, it may be a big issue for others and patients who want to preserve fertility may prefer a conservative treatment.

To be eligible for conservative treatment the endometrial cancer must be early-stage and the patient assessed to meet the following criteria:

1. Early stage cancer confined to the endometrium (it has not entered the myometrial (middle) layer of the uterus or only superficially entered it (Stage 1A). This is investigated by MRI, CT scan and pelvic ultrasound (trans-abdominal, trans-vaginal).

2. The endometrial cancer is not serous or clear cell type.

3. Well-differentiated cancer cells (A cancer cell that closely resembles the structure of the tissue it started in is well-differentiated. If cancer cells are poorly differentiated, it can complicate identifying the tissue they started in. i.e. it is clear the cancer originated in the endometrium).

4. No pelvic and para-aortic lymph node involvement.

5. No ovarian cancer.

6. No contraindications to medical treatments. A contraindication is when a medication, procedure, or surgery should not be used because it may be harmful to the patient. 

7. Patient strongly wishes to preserve fertility.

Conservative hormone treatments

Previously, the most common conservative treatment option for early stage endometrial cancer was hormone treatment with tablets (high dose oral progestins such as megestrol and medroxyprogesterone).

The majority of endometrial cancers develop because of an oversupply of oestrogen. Progestin in hormone treatment is known to suppress the oestrogen-triggered growth of endometrial cancer. Oral progesterone treatment may include side effects such as changes in appetite, acne, weight gain, headache, fluid retention, liver injury, depression, breast discomfort, or irregular bleeding. 

GnRH is another therapeutic hormonal approach in endometrial cancer. GnRH therapy decreases production of the hormone estrogen, to the levels women have after menopause for as long as it is taken. This may lead to regression of the cancer.

The most common treatment is through an intrauterine device (IUD) that slowly and steadily releases a progestin called levonorgestrel. Limited evidence also exists regarding treatment with metformin (an anti-diabetes drug that may also be a powerful anti-cancer drug). A clinical trial, called the feMMe trial, at the Queensland Centre of Gynaecological Research is currently investigating the use of IUD or metformin in early stage endometrial patients. An IUD provides very high doses of progestin to the local endometrium without serious system adverse effects that are experienced with oral progestins. 

Conservative surgery

Hysteroscopic resection, combined with hormone therapy, is another type of conservative treatment. Hysteroscopic resection involves resection of the tumour (cancerous cells), and a small layer of the myometrium underlying the tumour, and of the endometrium adjacent to the tumour.

Experimental treatments

A highly complex and rare surgical procedure is a uterus transplantation which involves removing the donor uterus and attaching the organ's veins and arteries to the transplant recipient. The patient who receives the donor organ needs to take oral immunosuppressant drugs and before the operation their eggs are fertilised through IVF. This procedure is pioneered in Sweden and still in the clinical research phase (around 60 procedures performed worldwide) and not yet offered in Australia.

Conservative treatment of endometrial cancer should be offered to young patients with early stage 1 endometrial cancer who wish to preserve fertility. There is no one type of hormone treatment that has been found to be superior therefore patients should discuss all their options with their gynaecological oncologist. Regular follow-up after conservative treatment is essential to monitor disease stability, progression or cancer recurrence.

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