Uterine Cancer: Risk Factors, Diagnosis and Management
Dr. Ainhoa Madariaga
Consultant Medical Oncologist, 12 de Octubre University Hospital (Madrid, Spain).
Uterine cancer, also called endometrial cancer (EC), is a gynecological malignancy that arises from the inner lining of the uterus which is medically known as endometrium. It is more common in North America and Western Europe due to lifestyle risk factors, whereas in India the incidence rate is low (2.4 cases per 100,000 women population) (1,2). Fortunately, most of these cancers present at an early stage and are associated with a good prognosis.
The most common symptom is abnormal vaginal bleeding which may include a change in the periods, bleeding between periods or bleeding after menopause. EC usually occurs after menopause, but it may also appear around the time menopause begins and during the menopausal transition. Experiencing an unusual vaginal bleeding, pain in the pelvic area or during sex should be brought to the doctor’s attention.
EC is often a hormone-sensitive disease thought to commonly arise in the context of excessive oestrogenic stimulation (3). Oestrogen is a female hormone mainly produced in the ovaries whose imbalance may cause changes in the endometrium and, eventually, lead to cancer. Classically, EC has been categorized in two types: type I (hormone-dependant) and type II (not oestrogen driven). The last subtype is less frequent, representing 10-20% of all EC; however, it is a more aggressive form that implies a poorer survival (4).
Risk factors for hyperoestrogenism include obesity, hormone therapy (such as tamoxifen, a medication commonly used for breast cancer treatment), polycystic ovarian syndrome and early menstruation/commencing menopause at a later age (5,6). Women who have never conceived fall also under the higher risk category (7). However, there are factors that provide protection against EC such as parity or oral contraceptive use, which reduces the risk of EC by 30 to 40% (8). On the other hand, little is known about risk factors for type II tumours, but may share risk factor profiles with oestrogen dependant tumours (4,9).
Additionally, around 3% of all EC depends on genetic factors related to mutations that are passed on from parents to offspring. Here, the Lynch syndrome (LS) plays a role. LS is a type of inherited cancer syndrome associated with a genetic predisposition to different cancer types such as EC or colorectal cancer. When familial history is highly suspicious of LS, genetic counselling is recommended (10). Therefore, those with several cases of these types of cancer in the same family should seek medical assistance.
The standard diagnostic work-up includes a physical examination and transvaginal ultrasonography with or without hysteroscopy (11). The hysteroscope is a lighted, flexible and thin camera device that allows for a visual examination of the inside cervix and uterus. Magnetic resonance imaging may be able to provide additional information on endometrial thickening or structural abnormalities as well as on surgical management. In addition, if an advanced stage is suspected, a computed tomography scan should be carried out.
In any case, the definitive diagnosis requires an endometrial tissue sample, usually obtained by curettage (12). This procedure involves cervical dilation with scraping of the endometrial lining. Once the diagnosis is reached, treatment should be carried out according to the patient´s condition. Surgery is the mainstay of the initial management and staging is based on pathological evaluation after surgery.
For the early-stage disease (stages I and II), surgery is the primary treatment. For most patients, the current surgical approach includes laparoscopic or robotic removal of the uterus (hysterectomy), cervix, fallopian tubes and ovaries (salpingo-oophorectomy) without vaginal cuff resection, and a lymph-node evaluation (10,13). Depending on the stage of disease and other risk factors, preventive radiotherapy and/or chemotherapy can be used to reduce risk of recurrence.
In the advanced-disease context (stages III and IV), surgery may be considered when complete resection is feasible with an acceptable side-effect and quality of life profile. Systemic therapy for advanced EC may include chemotherapy based on intravenous drugs (carboplatin/paclitaxel) or hormonal therapy, depending on the tumour characteristics. Currently, molecular characterization (a fingerprint of the tumour looking at gene and protein alterations) may be helpful to tailor treatment for early, advanced and recurrent disease.
Post-treatment surveillance is recommended for early detection of recurrent disease. The Society of Gynecologic Oncology (SGO) recommends follow-up symptom surveillance and pelvic examinations every three to six months for two years post-treatment, then every six months for three years, and annually thereafter (14).
Authors: Macarena Rey1, Ainhoa Madariaga1
1 Medical Oncology Department, 12 de Octubre Hospital, Madrid, Spain.
July 01, 2022
Dr. Macarena Rey
2011-2017: Degree in Medicine (MD) Universidad Complutense de Madrid, Facultad de Medicina (Medical School), Madrid, Spain • 2011: Award in the national ranking of top100 admission marks to university studies • 2015: Erasmus+ grant for European exchange programme (destination: Manchester Royal Infirmary, UK).
2017-2023: Medical Residency program in Medical Oncology • Centre: University Hospital 12 de Octubre, Madrid, Spain • Mentor: Luis Paz-Ares MD, PhD.
2020-2021: Molecular Oncology Master (MOM) • Degree awarding entity: University Rey Juan Carlos, Madrid, Spain in collaboration with the Spanish National Centre for Cancer Research (CNIO).
- 1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209–49.
- 2. Maheshwari A, Kumar N, Mahantshetty U. Gynecological cancers: A summary of published Indian data. South Asian J Cancer. 2016 Sep;5(3):112–20.
- 3. Makker V, MacKay H, Ray-Coquard I, Levine DA, Westin SN, Aoki D, et al. Endometrial cancer. Nat Rev Dis Primers. 2021 Dec 9;7(1):88.
- 4. Setiawan VW, Yang HP, Pike MC, McCann SE, Yu H, Xiang YB, et al. Type I and II endometrial cancers: have they different risk factors? J Clin Oncol. 2013 Jul 10;31(20):2607–18.
- 5. Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K, et al. Body Fatness and Cancer–Viewpoint of the IARC Working Group. N Engl J Med. 2016 Aug 25;375(8):794–8.
- 6. Lee M, Piao J, Jeon MJ. Risk Factors Associated with Endometrial Pathology in Premenopausal Breast Cancer Patients Treated with Tamoxifen. Yonsei Med J. 2020 Apr;61(4):317–22.
- 7. Wu QJ, Li YY, Tu C, Zhu J, Qian KQ, Feng TB, et al. Parity and endometrial cancer risk: a meta-analysis of epidemiological studies. Sci Rep. 2015 Sep 16;5:14243.
- 8. Lu KH, Broaddus RR. Endometrial Cancer. N Engl J Med. 2020 Nov 19;383(21):2053–64.
- 9. Felix AS, Weissfeld JL, Stone RA, Bowser R, Chivukula M, Edwards RP, et al. Factors associated with Type I and Type II endometrial cancer. Cancer Causes Control. 2010 Nov;21(11):1851–6.
- 10. Santoro A, Angelico G, Travaglino A, Inzani F, Arciuolo D, Valente M, et al. New Pathological and Clinical Insights in Endometrial Cancer in View of the Updated ESGO/ESTRO/ESP Guidelines. Cancers. 2021 May 26;13(11):2623.
- 11. Larish A, Kumar A, Weaver A, Mariani A. Impact of hysteroscopy on course of disease in high-risk endometrial carcinoma. Int J Gynecol Cancer. 2020 Oct;30(10):1513–9.
- 12. Lago V, Martín B, Ballesteros E, Cárdenas-Rebollo JM, Minig L. Tumor Grade Correlation Between Preoperative Biopsy and Final Surgical Specimen in Endometrial Cancer: The Use of Different Diagnostic Methods and Analysis of Associated Factors. Int J Gynecol Cancer. 2018 Sep;28(7):1258–63.
- 13. Abu-Rustum NR, Yashar CM, Bradley K, Campos SM, Chino J, Chon HS, et al. NCCN Guidelines® Insights: Uterine Neoplasms, Version 3.2021. J Natl Compr Canc Netw. 2021 Aug 1;19(8):888–95.
- 14. Hamilton CA, Pothuri B, Arend RC, Backes FJ, Gehrig PA, Soliman PT, et al. Endometrial cancer: A society of gynecologic oncology evidence-based review and recommendations. Gynecol Oncol. 2021 Mar;160(3):817–26.