Endometrial cancer: advanced stages and targeted treatment

Endometrial cancer, also known as uterine or womb cancer, is a cancer of the uterus that is formed by abnormal cell growth inside the tissue of the womb, called the endometrium. In its later stages, it can be difficult to treat, but targeted therapies may be able to provide new hope for patients in their fight against the cancer. In this article, a leading medical oncologist explains the stages of endometrial cancer and how targeted treatment can be used against it.

What are the causes and signs of endometrial cancer?

It is most common in those who have gone through menopause, and is more likely in those who have a high level of oestrogen – which could be due to hormone replacement therapy (HRT), never having given birth, or polycystic ovary syndrome (PCOS). Those who have a family history of gynaecological cancers, diabetes, or have had radiotherapy on their pelvis also have a higher risk of developing endometrial cancer.

The symptoms of endometrial cancer include:

• Bleeding or spotting outside of regular periods, or after menopause
• Unusually heavy periods
• Changes to discharge (smell, texture, colour)
• A lump or swelling in the abdomen or pelvis
• Pain in the pelvis
• Pain during sex

What are the stages of endometrial cancer?

The progression of cancers tends to be grouped into four stages, often written with Roman numerals. This is used to describe the size of tumours and the extent of the spread of cancer.

1. Stage I of endometrial cancer means that the tumour is still isolated to the womb, and is growing into the muscle wall (myometrium). This is the earliest stage and the easiest to treat. Surgery is the first line of treatment for this stage because it can remove the tumour and any nearby cancerous cells in one fell swoop. In the case of endometrial cancer, this surgery is a hysterectomy, which is the removal of the uterus and cervix. It can be done in conjunction with a bilateral salpingo-oophorectomy (BSO) which removes the ovaries and fallopian tubes, as an extra precaution against the cancer, but will incite menopause immediately within the patient. Of course, a hysterectomy means that the patient will no longer be able to get pregnant. If the patient is looking to have children borne from pregnancy, there are medication options to stall the need for a hysterectomy whilst they try to get pregnant or freeze their eggs for future possibilities.
2. Stage II means that the cancer has spread from the main body of the uterus and is growing into the supporting connective tissue of the cervix, but hasn’t spread any further. Again, surgery is recommended as a first step, in this case a radical hysterectomy, where the uterus, nearby tissues, and the upper portion of the vagina are removed. It may be combined with a BSO. Surgery is often followed by radiation therapy to kill any dispersed cancerous cells.
3. Stage III means that the cancer has spread out beyond the uterus but still remains in the pelvic tissues, like the vagina. The same technique for treatment as above applies, but they may do radiation therapy or chemotherapy (or both) before any surgery in order to shrink the tumours before trying to remove them in a hysterectomy, which may include the removal of the pelvic and para-aortic lymph node (LND).
4. Stage IV means that the cancer has grown into the bladder, rectum, bowels, or even beyond the pelvis, like the liver, lungs, or other organs. At this point, surgery may not be sufficient to get out all of the cancerous tissues and cells, so radiation and chemotherapy are employed to slow it down and allow patients some more time. However, there are innovations in the treatment of endometrial cancer, such as targeted therapy.

What is targeted therapy?

Targeted therapy for endometrial cancer is still new, so many times it is utilised as part of clinical trials or to treat cancer that has recurred. These are treatments that are designed to attack or halt cancer cells specifically, whilst sparing normal healthy cells as much as possible. These therapies use drugs that can identify the proteins, receptors, or genes that are typical of cancer cells and tissues.

• Monoclonal antibodies (MABs), which are synthetic copies of antibodies that target intruder proteins (antigens), stopping them from dividing, transporting cancer drugs or radiation to cancer cells, or assisting the body’s own antibodies find and kill cancer cells. On the market currently are trastuzumab, pertuzumab, bevacizumab, rituximab. This are administered through intravenous infusion or injection.
• Cancer growth blockers, which stop cancer cells from dividing and growing by disrupting growth factor chemicals in the body, such as tyrosine kinase, proteasome, and mTOR. These tend to be administered as tablets that are swallowed a couple of times a day, but there are also options in the form of intravenous infusions and injections.
• Drugs that block cancer blood vessel growth (anti-angiogenics) stop tumours from forming blood vessels, which helps to ensure that they do not get nutrients from the body’s blood and inhibits their growth, maybe even shrinking them. Tyrosine kinase inhibitors can be used for this purpose, such as sunitinib, sorafenib, and axitinib. These can be administered mainly as tablets or intravenous infusion.
• Poly-ADP ribose polymerase (PARP) inhibitors, which stops the PARP protein from doing its job of healing damaged cells, so that cancer cells that are damaged die instead of repairing. This is thought to be the most effective for those with a mutation of their BRCA1 or BRCA2 genes, which makes them more at risk for certain cancers. The cancerous cells within these gene mutations are already faulty so PARP inhibitors are particularly effective against them in these kinds of patients, such as olaparib, niraparib, rucaparib, and alazoparib.These are administered orally as tablets.

Targeted therapy can be very effective, but only if it works. It is not a suitable treatment for every patient, or every case of endometrial cancer. The side effects can be quite abrasive, such as nausea, diarrhoea, dry skin, heart damage, and greying hair.

If you would like more information about endometrial cancer and targeted therapy, consult with a specialist today via Top Doctors.