Endometrial cancer: advanced stages and targeted treatment

Written in association with: Professor Susana Banerjee
Published: | Updated: 18/11/2024
Edited by: Jessica Wise

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, Dr Susana Banerjee, 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 Dr Banerjee today via her Top Doctors profile.

By Professor Susana Banerjee
Medical oncology

Prof Susana Banerjee is a highly-regarded, leading London consultant medical oncologist and research lead for the Gynaecology Unit at The Royal Marsden. She specialises in treating patients with ovarian cancer and other gynaecological cancers, such as advanced endometrial cancer and cervical cancer. Additionally, she is a professor in Women’s Cancers and team leader at the Institute of Cancer Research.

Prof Banerjee graduated with a first-class from St John’s College, University of Cambridge, and completed her medical training at Royal Free Medical School where she was a University of London gold medal finalist. She was awarded an Avon Breast Cancer Crusade Clinical Fellowship for laboratory research and gained a PhD from The Institute of Cancer Research, University of London. Upon completing specialist training at The Royal Marsden, she was appointed as a consultant in 2011. Dr Banerjee offers private consultation for patients nationally and internationally for expert opinions and treatment.

In addition to her clinical work, Prof Banerjee has been involved in multiple national and international specialist groups including the National Cancer Research Institute (NCRI) Gynaecological Cancers Clinical Studies Group, European Organisation for Research and Treatment of Cancer (EORTC) Executive Steering Committee for Gynaecological Cancers, ESGO (European Society of Gynaecological Oncology) Congress Faculty, and International Gynecologic Cancer Society Scientific Program Committee.

Dr Banerjee served on the European Society of Medical Oncology (ESMO) Executive Board as director of membership (2020-2022) and was also part of the Women for Oncology Committee. She chairs the ESMO Resilience Task Force. She was track chair for Gynaecological Cancers for the ESMO Congress 2018, scientific co-chair for ESMO Asia 2018, and co-chair of the ESMO Gynaecological Cancers Congress 2021-2024.

Prof Banerjee is global lead of several international clinical trials, national chief investigator for more than 30 clinical studies and has over 180 peer-reviewed publications including in New England Journal of Medicine, Lancet Oncology, and Nature Communications. In addition to being a chief investigator on numerous national and international clinical trials, she is on the advisory board for the international journal Nature Reviews Clinical Oncology and on the editorial boards of Cancer Treatment Reviews and ESMO Open. She has acted as a NICE clinical expert and currently is a medical advisor for the Ovacome UK Charity.

Dr Banerjee was awarded the San Antonio Breast Cancer Symposium Novartis Oncology Basic Science Award for her research in 2007 and has given several international presentations. Other prizes include the Association of Cancer Physicians McElwain Prize and the Sir Antony Driver Prize. She was also highly commended for the Pfizer British Oncology Association Young Investigator Award. In 2023, Prof Banerjee received the Fellow of ESMO (FESMO) Award.

She received research funding from Lady Garden Foundation, Royal Marsden Cancer Charity, and Wellbeing of Women Charities. She is a fellow of the Royal College of Physicians (FRCP) and President Elect of the Royal Society of Medicine Oncology section.

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