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Endometrial Cancer- Diagnosis and Treatment

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What is Uterine Cancer (Endometrial Cancer)?

Endometrial cancer or uterine cancer refers to the abnormal growth of the epithelial cells, resulting in a tumor. It further invades the local tissue and spreads or metastasizes to distant sites or organs. This type of cancer begins in the layer of cells that form the uterus’ lining (endometrium). 

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The uterus is a pear-shaped organ in the pelvic cavity. The main function is to carry the fetus until it develops enough to be delivered out into the world. It is a muscular organ that is lined by epithelium, known as the endometrium. In the endometrium, the zygote is implanted and successively develops into an embryo and then a fetus. Beneath lays the myometrium, made of smooth muscle cells. Myometrium provides the power for contraction during childbirth. It is covered on the outside by a fibrous tissue known as the serosa.

Endometrial cancer is the third most common cancer in Indian women. But the incidence of this cancer in India is much lower than in the West. The most common type of endometrial cancer is endometrioid carcinoma. It contributes to around 80 % of the country’s endometrial cancer cases. Endometrial cancer is often detected in the early stages as it causes abnormal vaginal bleeding.

Uterine Cancer Symptoms

  • Abnormal uterine bleeding may be in-between menses, spotting of blood in the inner garments, or irregular menstrual periods. In post-menopausal women, any bleeding is abnormal.
  • Any abnormal vaginal discharge may range from pink and watery to thick, brown, and foul-smelling.
  • Pelvic pain.
  • Loss of appetite.
  • Fatigue and Exhaustion.
  • Abdominal cramping and bloating.
  • A quick feeling of satiety on eating.
  • An enlarged uterus is detected during the pelvic exam.

Uterine Cancer Stages

Uterine or endometrial cancer is often diagnosed in the early stages itself owing to its symptoms. Based on the extent of spread of cancer, endometrial cancer is categorized into different stages as follows :

  • Stage I – cancer is confined to the uterus and has not spread to the other parts of the body. It is localized to the endometrium and one-half of the myometrium.
  • Stage II – Cancer has spread from the uterus to the cervix but not to the other parts of the body.
  • Stage III – Cancer has spread beyond the uterus to the tissues of the fallopian tubes, ovaries, vagina, regional pelvic lymph nodes, or para-aortic lymph nodes. In this stage, the tumor cells are confined to the pelvic region.
  • Stage IV – Cancer has spread to the other parts of the body like the rectum, bladder, lymph nodes in the groin area, bone, or lungs.

Uterine Cancer Types

Most of the cases of endometrial cancers are adenocarcinomas. These are cancers that develop from the glandular tissue. Other less common types of endometrial or uterine cancer are :

  • Uterine carcinosarcoma – It is a highly aggressive and rare cancer that displays the histological features of both endometrial carcinoma and sarcoma when viewed under a microscope. The chances of developing this cancer are high if the patient has been previously exposed to pelvic radiation.
  • Squamous cell carcinoma of the endometrium – It is uncommon cancer that is either primary or secondary to cervical cancer. In this type, the squamous cell carcinoma spreads superficially to the uterus’s inner surface and replaces the endometrium with the carcinoma cells. It usually occurs in postmenopausal women. 
  • The endometrium’s small cell carcinoma is a type of malignant neuroendocrine tumor that arises most commonly in the cervix. This carcinoma metastasizes to other distant organs much more frequently than the other carcinomas. Visual impairment and kidney membranous glomerulonephritis are associated with this carcinoma as it increases the hormones or serum antibody levels in the body.
  • Transitional cell carcinoma of the endometrium is a scarce type of carcinoma commonly in the ovary.
  • Serous carcinoma of the endometrium – It is an aggressive type of endometrial cancer that is poorly diagnosed and has a 5-year survival rate as low as 55 %.

Endometrial cancers are broadly classified into two main types, as shown below :

  • Type 1 – Cancer is relatively slow-growing and doesn’t spread to the other tissues quickly. It accounts for more than 80 % of the reported cases and is often associated with hormonal imbalance.
  • Type 2 – Cancer is more aggressive and tends to spread outside the uterus. It accounts for around 20 % of the reported cases but has a poor prognosis than type 1 endometrial cancer.

What Causes Uterine Cancer?

The exact etiology of endometrial cancer remains unknown. Doctors believe that hormonal imbalances due to estrogen and progesterone levels affect the endometrium and facilitate the endometrial cells to multiply without any check. Genetics also play a role in developing endometrial cancer.

Genetic mutations in the MLH1, PMS2, MSH2, and MSH6 genes are responsible for Lynch syndrome, and these mutations run in the family. Women whose first-degree relatives are diagnosed with Lynch syndrome are more often diagnosed with endometrial cancer than those whose mothers are not diagnosed with Lynch syndrome. 

What are the Risk Factors?

The non-modifiable risk factors of endometrial cancer are :

  • Age – Older women, especially those between 45 and 74, are at a higher risk than younger women.
  • Genetics – Females with MLH3, MSH6, TGBR2, PMS1, PMS2, BRCA 1, and BRCA 2 mutation are more at risk for developing endometrial cancers.
  • Lynch Syndrome – The risk of developing endometrial cancer for women with Lynch syndrome lies around 20 % to 50 %.
  • Family History – The risk of endometrial cancer is increased by 82 % if the patient’s mother, sister, or daughter was diagnosed with endometrial cancer.
  • Increased menstrual cycles – Early beginning of menstruation before age 12 and late menopause increases the number of menstrual cycles in a woman’s lifetime. This is considered a risk factor for endometrial cancer.
  • Ovarian tumors – Granulosa cell tumor is a type of ovarian tumor that releases estrogen at higher levels. This creates a hormone imbalance that stimulates the endometrium and eventually causes endometrial cancer.
  • Polycystic ovarian syndrome (PCOS) – Women with PCOS have abnormal hormone levels such as high androgen and estrogen levels and lower progesterone levels. This, in turn, increases the likelihood of developing endometrial cancer. 

The modifiable risk factors of endometrial cancer are :

  • Pregnancy – Late pregnancy, having no child, and infertility poses a higher risk as this elevates the levels of estrogen in the woman. One or more full-term pregnancies reduce the risk, causing the hormone balance to shift more towards progesterone.
  • Lack of breastfeeding – Exclusive breastfeeding for at least 6 months reduces the risk of developing endometrial cancer by 11 %.
  •  Hormone Replacement Therapy – The symptoms of post menopause are treated using estrogen, which increases the risk of endometrial cancer. Women taking progesterone alone are not at risk of developing endometrial cancer.
  • Diet and exercise – A high-fat diet leads to an increased risk of hyperplasia and endometrial cancer development. Lack of physical activity and women who spend more time sitting have a higher risk than women who exercise regularly.
  • Obesity – Endometrial cancer is twice as common in overweight women as women who maintain a healthy weight. Gaining weight with age and weight cycling are linked to a higher risk of endometrial cancer after menopause.

How Is Endometrial Cancer Diagnosed? 

The gynecologist will first question the patient about her medical history and symptoms experienced. Following this, a pelvic exam will be conducted to look for abnormalities in the uterus and other reproductive organs. Other commonly used diagnostic tests are :

  • Pelvic ultrasound – A transducer is moved over the abdomen’s skin to get good pictures of the uterus, ovaries, fallopian tubes, and bladder. To get clear images of the bladder, it must be full, and for this purpose, the patient is asked to drink lots of water before the exam.
  •  A transvaginal ultrasound exam is a type of pelvic ultrasound in which the doctor inserts an ultrasound probe into the vagina. This probe produces sound waves that help transmit pictures of the inside of the pelvis onto a monitor. The ultrasound features that are unique to endometrial cancer are irregular endometrial thickening and intrauterine fluid collection.
  •  Saline infusion sonogram or Hysterosonogram – A small tube is used to put saline or saltwater into the uterus before the ultrasound. This helps the doctor to see the uterus more clearly.
  • Endometrial biopsy – A small piece of tissue from the uterus’s lining is removed and sent to the pathologist for further analysis. This procedure is used to identify the cause of heavy or irregular menstrual bleeding and also to check if the hormone levels are balanced or not.
  •  Dilatation and Curettage (D&C) – In this procedure, the doctor uses small instruments or medications like misoprostol to dilate the cervix and then uses a curette ( a surgical instrument) remove the uterine tissue. The patient is anesthetized before this test. This procedure is usually done if the biopsy results are unclear.
  • Hysteroscopy – In this procedure, a hysteroscope or a thin, lighted tube is inserted into the vagina to examine the cervix and the inside of the uterus. It provides a good visualization of the whole uterine cavity without any cervical dilation and anesthesia. It is often combined with endometrial biopsy for the diagnosis of endometrial cancer with high diagnostic accuracy.

Screening Tests to determine if cancer has spread or not :

  • CA-125 blood test – CA-125 (Cancer Antigen – 125) is a protein released into the bloodstream by most endometrial and ovarian cancers. High levels of CA-125 in women diagnosed with endometrial cancer suggest that cancer has spread beyond the uterus. This test is not a diagnostic test and hence is not done for all patients with endometrial cancer.
  • Complete blood count – Lower red blood cell counts indicate endometrial cancer as this cancer causes bleeding.
  • Chest x-ray – This is done to determine if cancer has spread to the chest or not.
  • Computed Tomography (CT) Scan – This scan provides detailed images of the inside of the body. It is done to ascertain the recurrence of cancer and determine the extent to which cancer has spread.
  • Magnetic resonance imaging (MRI) scan helps determine how far cancer has spread within the uterus and to find any enlarged lymph nodes.
  • Positron Emission Tomography (PET) scan is done for advanced cases of endometrial cancer to determine the exact location of cancer spread.

Treatment: how is it treated?

The standard treatments available for endometrial or uterine cancer are as follows:

  • Surgery is the most common treatment for endometrial cancer and involves removing the uterus and ovaries, and fallopian tubes. The surgical procedures that are often used for this purpose are:
  • Total hysterectomy – Removal of the uterus along with the cervix either via the vagina ( vaginal hysterectomy) or via the abdomen (abdominal hysterectomy) or by using a laparoscope (total laparoscopic hysterectomy).
  • Radical hysterectomy – The uterus, cervix, and part of the vagina are removed. The nearby lymph nodes, fallopian tubes, and ovaries may also be removed.
  • Lymph node dissection – Lymph nodes in the pelvic region are removed for therapeutic or diagnostic purposes. A sample of tissue from these lymph nodes is analyzed to check for the presence of cancerous cells.
  • Chemotherapy is not used for stage I or II endometrial cancers but is used for advanced-stage cancers. The drugs commonly used include paclitaxel, carboplatin, doxorubicin, cisplatin, and docetaxel. These drugs are given orally or intravenously for a few cycles to kill the cancer cells that have spread beyond the endometrium to other parts of the body.
  • Radiation therapy High energy x-rays or other radiations are used to kill the cancer cells or keep them from growing. External radiations or internal radiations may be used to elicit this action. This therapy is also used to improve the quality of life and relieve the symptoms of endometrial cancer.
  •  Targeted Therapy causes less harm to normal cells than radiation therapy or chemotherapy and uses monoclonal antibodies, mTOR inhibitors, and signal transduction inhibitors to treat endometrial cancer. These are often used to treat stage III, stage IV, and recurrent endometrial cancer. Monoclonal antibodies like bevacizumab are given by infusion and attach to the specific target on the cancer cells to block their growth and keep them from spreading. mTOR inhibitors like Everolimus and ridaforolimus control cancer cells’ cell division and prevent new blood vessels’ growth that the tumor cells need for growing. Signal transduction inhibitors like metformin are currently being studied as they can block the transduction of signals from one molecule to another inside the cell.
  • Immunotherapy – In this therapy, immune checkpoint inhibitors like Pembrolizumab are used. This inhibitor targets the PD-1 protein present on the immune cells like the T-cells. By blocking this protein, it boosts the immune response against cancer cells. It is used in women with endometrial cancer linked to genetic mutations. This therapy is often used in combination with targeted therapy.
  • Hormone Therapy – In this treatment, hormones and hormone-blocking drugs like progestin, tamoxifen, aromatase inhibitors, and luteinizing hormone-releasing agonists are used to treat advanced and recurrent endometrial cancer. Progestin is the main hormone used for treating endometrial cancer as it slows down the growth of the cancer cells. The commonly used progestins are Medroxyprogesterone acetate (injection or pill) and Megestrol acetate (pill or liquid). Tamoxifen controls the growth of the cancer cells by acting against estrogen. Luteinizing hormone-releasing agonists like Goserelin and leuprolide are given as shots every 1 to 3 months to lower the estrogen levels in women whose ovaries have not been removed during surgery. Aromatase inhibitors like letrozole, anastrozole, and exemestane stop estrogen production by the fat tissues in the body and are used in women who cannot undergo surgery.

Ways to lower the risk of endometrial cancer:

There are no definite ways to prevent endometrial cancer. However, managing a healthy weight and maintaining regular physical activity is lowers the risk of developing endometrial cancer. 

Abnormal vaginal bleeding and other indicative signs must be reported to the doctor at the earliest. Proper consultation must be done before going for hormone replacement therapy. The pros and cons of using estrogen alone versus estrogen combined with progesterone must be kept in mind before opting for the therapy. Genetic testing for Lynch syndrome may be done if the patient has a family history of this syndrome. If the patient is diagnosed with Lynch syndrome, the doctor usually suggests removing the uterus, fallopian tubes, and ovaries to prevent cancer. 

Obesity, hypertension, and diabetes can contribute to long-term health risks for women with type 1 endometrial cancer. Proper diet and lifestyle modifications must be done to keep these conditions in check.

FAQs :

1. Is it curable?

  • Endometrial cancer is curable as the symptoms manifest in the early stages itself. However, if cancer has spread to the other parts of the body, as in stage IV cancer, then the chances of complete recovery are greatly reduced.

2. What are the survival chances of endometrial cancer?

  • The 5- year survival rates for endometrial cancer are 95 % if cancer has not spread outside the uterus, 69 % if cancer has spread to the nearby structures and lymph nodes, and 17 % if cancer has metastasized or is categorized as stage IV cancer.

3. What is the cost of treatment for endometrial cancer in India?

  • The average cost of endometrial cancer surgery is around 2 lakhs, while radiation therapy costs around 2.5 lakhs for two cycles.

4. Which are the hospitals to get cancer treatment in India?

  1. Asian Institute of Oncology
  2. S.L.Raheja Hospital, Raheja Hospital Road, Mahim, Mumbai 
  3. Cancer Institute (WIA),  Adyar, Chennai
  4. Jaslok hospital research Centre, Mumbai
  5. Dharamshila Cancer Hospital & Research Centre, Vasundhara Enclave, New Delhi
  6. Dr. B. Borooah Cancer Institute, Gopinath Nagar, Guwahati
  7. Dr. Rai Memorial Cancer Institute 562, Anna Salai, Chennai, Tamil Nadu
  8. Rajkot Cancer Society, Mr. N.P. Cancer Institute, Raiya Road, Rajkot, Gujarat
  9. Regional Cancer Centre, Medical College Campus, P.B.2417, Thiruvanthapuram, Kerala.
  10. Tata Memorial Centre, Dr. Ernest Borges Marg, Parel, Mumbai
  11. The Gujarat Cancer & Research Insitute, M.P. Shah Cancer Hospital, New Civil Hospital Compound Asarwa, Ahmedabad
  12. Rajiv Gandhi Cancer Hospital & Research Institute, Sector 5, Rohini, Delhi
  13. Bhagwan Mahaveer Cancer Hospital & Research Centre, Jawaharlal Nehru Marg, Jaipur

Other reputed Cancer Hospitals and Institutes in India:

  1. Regional Centre for Cancer Research, Adyar, Chennai.
  2. Regional Centre for Cancer Research and Treatment, Mangalabag, Cuttack – 753 007.
  3. Rotary Cancer Centre, 117/K/11, Gutaiya, G.T.Road, Kanpur  – 208 002, India
  4. Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Sector 22, Kharghar, Navi Mumbai – 410 210
  5. Amala Cancer Research Centre, Amalangar, Trichur.
  6. Bose Institute
  7. Cancer Treatment & Research Centre, Lion District 324 C-1, Seethammadhara North Extn., Visakhapatnam – 530 013 (AP).
  8. Chittaranjan Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700026
  9. Christian Cancer Centre, Kakinada Pithapuram Road, Kakinada – 533 003, Andhra Pradesh
  10. All India Institute of Medical Sciences, Ansari Nagar, New Delhi – 110016.
  11. Dr. Bhubaneshwar Barooah Cancer Institute, Gopinath Nagar, Guwahati – 781 016, Assam.
  12. G.V.N. Cancer Centre, No.16, Kiledar Street, Tiruchirapalli – 620 002, Tamil Nadu.
  13. Goa Cancer Society, GM Cancer Hospital & Research Institute, Dr. E. Borges Road, Dona Paula – 403 004, Goa.
  14. Indian Rly. Cancer Institute & Research Centre, N.E. Railway, Lahartara, Varanasi – 221 002, Uttar Pradesh.
  15. Institute of Cytology & Preventive Oncology, I-7, Sector 39, P.O.Box No. 544, Near Degree College, Opposite City Centre, Noida – 201 301, Uttar Pradesh.
  16.  International Cancer Centre,  Neyyoor,  Tamilnadu  – 629 802.
  17. International Network for Cancer, Treatment, & Research Room No. 127A, Sir Gangaram Hospital, Rajinder  Nagar, New  Delhi -110 060.
  18. J.K. Cancer Institute (C.S.V.M. Medical College), Kanpur  – 208 002, Uttar Pradesh.
  19. Jagdish Cancer & Research Centre, 3-6-20, Tirumala Apts. Skyline Lane, Basheer Bagh, Hyderabad.
  20. Jawaharlal Nehru Cancer Hospital, & Research Centre, Idgah Hills, PB No. 32 Bhopal – 462 001.
  21. Mohan Das Oswal Cancer Treatment & Research Centre, G.T. Road, Sherpur, Ludhiana – 141 009, Punjab.

Cancer Specialists

Top 20 Cancer Specialists in India

  1. Dr. Suresh H. Advani
  2. Dr. Harit Chaturvedi
  3. Dr. Kapil Kumar 
  4. Dr. Ashok Vaid
  5. Dr. Aruna Chandrasekaran
  6. Dr. Rajesh Mistry
  7. Dr. S Hukku
  8. Dr. Bidhu K Mohanti
  9. Dr. Vinod Raina
  10. Dr. Sabyasachi Bal
  11. Dr. Hari Goyal
  12. Dr. Tejinder Kataria
  13. Dr. Rajesh Jindal
  14. Dr (Col.) R Ranga Rao
  15. Dr. Jyoti Wadhwa
  16. Dr. Sandeep Mehta
  17. Dr. Sunil Kumar Gupta
  18. Dr. Sankar Srinivasan
  19. Dr. PL Kariholu
  20. Dr. Subodh Chadra Pnndea

5. Is endometrial cancer hereditary?

  • Around 5 % of the endometrial cancer cases in the world are hereditary. Lynch syndrome and Cowden syndrome are two inherited syndromes known to increase the risk of endometrial cancer in women. These syndromes are due to genetic mutations and are passed on in the family.  

6. Is abnormal vaginal bleeding a sign of endometrial cancer?

  • Abnormal vaginal bleeding ranging from watery and blood-streaked flow to a flow that contains more blood, is an early sign of endometrial cancer. This is due to a hormonal imbalance as a result of too much estrogen in the body.

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