Endometrial Cancer Treatment

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief:  Ogechukwu Hannah Nnabude, MD

## Treatment

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Surgery

About 90% of women with endometrial cancer are treated with some form of surgery. [1] It is most often the initial treatment for endometrial cancer. Surgical treatment typically consists of hysterectomy with bilateral salpingo-oophorectomy, which is the surgical removal of the uterus, ovaries, and Fallopian tubes. In the United States,lymphadenectomy is routinely performed for all stages of endometrial cancer, However, in the United Kingdom, the lymph nodes are typically only removed with disease of stage II or greater. [2] The benefit of lymphadenectomy in stage I disease is still being contested. [3] Women who undergo lymphadenectomy are at risk of morbidity related to surgery or formation of lymphoedema/lymphocyst. [4] In stage III and IV cancers, cytoreductive surgery is often the management of choice, [5] and omental biopsy may also be performed. [6] Surgery can be done as part of palliative therapy in patients with stage IV disease in which there is distant metastasis. [3] The prognosis for stage III, stage IV, and recurrent endometrial cancers may be improved with maximum surgical debulking, especially if it is performed till tumor is > 1 cm. [7] [8] [9] [10] [11] [12] [13] [14] [15] While laparotomy is the traditional surgical procedure, laparoscopic surgery is associated with reduced operative morbidity and similar overall and disease free survival and is the preferred method in patients that are suspected to have early stage primary endometrial cancer. [6] Contraindications to surgery occur in about 5–10% of cases and include: [3]

* inoperable tumor
* massive obesity
* high-risk operations
* desire to preserve fertility

The side effects of surgical treatment include temporary incontinence, lymphedema and sexual dysfunction.

Adjuvant Therapies

The use of other therapies after surgery is called adjuvant therapy.[5] These include radiation therapy and chemotherapy. One or both may be used and is often considered in cases of high-risk or high-grade cancers.

Radiotherapy

Adjuvant radiotherapy is often used in stage I and stage II endometrial cancer. It can be delivered via external beam radiotherapy or via vaginal brachytherapy, which is the preferred route due to its lower toxicity. External beam radiotherapy can be used to treat cancer remnants in the pelvis following surgery, while vaginal brachytherapy is used to treat cancer remnants that are located in the vagina. Although external beam radiotherapy significantly reduces the rate of relapse in the pelvis, overall survival and metastasis rates are not improved. [16] Overall, vaginal brachytherapy provides a better quality of life than external beam radiotherapy. [3] Brachytherapy and/or external beam radiotherapy can also be used when hysterectomy is contraindicated. [3]

Chemotherapy

This often involve the use of a combination of paclitaxel (or other taxanes like docetaxel), doxorubicin (and other anthracyclines), and platins (particularly cisplatin and carboplatin). Adjuvant chemotherapy has been found to increase survival in stage III and IV cancer more than added radiotherapy. [5] [3] [1] Mutations in mismatch repair genes, like those found in Lynch syndrome, can lead to resistance against platins. [17] Side effects of chemotherapy include neutropenia, alopecia, and gastrointestinal disturbances. [5] Palliative chemotherapy may also be used in patients in which surgical treatment is either not feasible or helpful. Use of chemotherapy at higher doses is associated with longer survival. [5] [1]

Hormonal therapy

Previously thought to be useful in most cases, hormonal therapy is now considered to helpful in only certain types of endometrial cancer. [16] [5] About 25% of metastatic endometrioid cancers show a response to progestins. Since endometrial stromal sarcomas typically have estrogen, progestin receptors, or both, they may be treated with with hormonal agents. Progestin receptors function as tumor suppressors in endometrial cancer cells. [18] Preliminary research and clinical trials have shown these treatments to have a high rate of response even in metastatic disease. [19]

Monitoring

CA-125 is a tumor marker that can be monitored for elevation in endometrial cancer and can be used to determine the response to therapy, especially in serous cell cancer or advanced disease. [20] Periodic MRIs or CT scansmay be beneficial in advanced disease. Pelvic examinations are recommended to be conducted every three to four months for the first two years following treatment, and every six months for the next three years. [3] PET/CT scanning is recommended if there is a suspicion of recurrence. [3]

References

1. ↑ 1.0 1.1 1.2 Vale CL, Tierney J, Bull SJ, Symonds PR (2012). "Chemotherapy for advanced, recurrent or metastatic endometrial carcinoma". Cochrane Database Syst Rev (8): CD003915. doi:10.1002/14651858.CD003915.pub4. PMC 7104534 Check `|pmc=` value (help). PMID 22895938.CS1 maint: Multiple names: authors list (link)
2. ↑ Saso S, Chatterjee J, Georgiou E, Ditri AM, Smith JR, Ghaem-Maghami S (2011). "Endometrial cancer". BMJ. 343: d3954. doi:10.1136/bmj.d3954. PMID 21734165.CS1 maint: Multiple names: authors list (link)
3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Colombo N, Preti E, Landoni F, Carinelli S, Colombo A, Marini C | display-authors=etal (2013) Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 24 Suppl 6 ():vi33-8. DOI:10.1093/annonc/mdt353 PMID: 24078661
4. ↑ Frost JA, Webster KE, Bryant A, Morrison J (2017). "Lymphadenectomy for the management of endometrial cancer". Cochrane Database Syst Rev. 10: CD007585. doi:10.1002/14651858.CD007585.pub4. PMC 6485923. PMID 28968482.CS1 maint: Multiple names: authors list (link)
5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 Galaal K, Al Moundhri M, Bryant A, Lopes AD, Lawrie TA (2014). "Adjuvant chemotherapy for advanced endometrial cancer". Cochrane Database Syst Rev (5): CD010681. doi:10.1002/14651858.CD010681.pub2. PMC 6457820. PMID 24832785.CS1 maint: Multiple names: authors list (link)
6. ↑ 6.0 6.1 Galaal K, Donkers H, Bryant A, Lopes AD (2018) Laparoscopy versus laparotomy for the management of early stage endometrial cancer. Cochrane Database Syst Rev 10 ():CD006655. DOI:10.1002/14651858.CD006655.pub3 PMID: 30379327
7. ↑ Goff BA, Goodman A, Muntz HG, Fuller AF, Nikrui N, Rice LW (1994). "Surgical stage IV endometrial carcinoma: a study of 47 cases". Gynecol Oncol. 52 (2): 237–40. doi:10.1006/gyno.1994.1038. PMID 8314145.CS1 maint: Multiple names: authors list (link)
8. ↑ Bristow RE, Zerbe MJ, Rosenshein NB, Grumbine FC, Montz FJ (2000). "Stage IVB endometrial carcinoma: the role of cytoreductive surgery and determinants of survival". Gynecol Oncol. 78 (2): 85–91. doi:10.1006/gyno.2000.5843. PMID 10926785.CS1 maint: Multiple names: authors list (link)
9. ↑ Chi DS, Barakat RR (2001). "Surgical management of advanced or recurrent endometrial cancer". Surg Clin North Am. 81 (4): 885–96. doi:10.1016/s0039-6109(05)70172-9. PMID 11551132.
10. ↑ Bristow RE, Zahurak ML, Alexander CJ, Zellars RC, Montz FJ (2003). "FIGO stage IIIC endometrial carcinoma: resection of macroscopic nodal disease and other determinants of survival". Int J Gynecol Cancer. 13 (5): 664–72. doi:10.1046/j.1525-1438.2003.13385.x. PMID 14675352.CS1 maint: Multiple names: authors list (link)
11. ↑ Lambrou NC, Gómez-Marín O, Mirhashemi R, Beach H, Salom E, Almeida-Parra Z; et al. (2004). "Optimal surgical cytoreduction in patients with Stage III and Stage IV endometrial carcinoma: a study of morbidity and survival". Gynecol Oncol. 93 (3): 653–8. doi:10.1016/j.ygyno.2004.03.015. PMID 15196860.CS1 maint: Multiple names: authors list (link)
12. ↑ Awtrey CS, Cadungog MG, Leitao MM, Alektiar KM, Aghajanian C, Hummer AJ; et al. (2006). "Surgical resection of recurrent endometrial carcinoma". Gynecol Oncol. 102 (3): 480–8. doi:10.1016/j.ygyno.2006.01.007. PMID 16490236.CS1 maint: Multiple names: authors list (link)
13. ↑ Bristow RE, Santillan A, Zahurak ML, Gardner GJ, Giuntoli RL, Armstrong DK (2006). "Salvage cytoreductive surgery for recurrent endometrial cancer". Gynecol Oncol. 103 (1): 281–7. doi:10.1016/j.ygyno.2006.03.011. PMID 16631236.CS1 maint: Multiple names: authors list (link)
14. ↑ Shih KK, Yun E, Gardner GJ, Barakat RR, Chi DS, Leitao MM (2011). "Surgical cytoreduction in stage IV endometrioid endometrial carcinoma". Gynecol Oncol. 122 (3): 608–11. doi:10.1016/j.ygyno.2011.05.020. PMID 21664663.CS1 maint: Multiple names: authors list (link)
15. ↑ Papadia A, Bellati F, Ditto A, Bogani G, Gasparri ML, Di Donato V; et al. (2015). "Surgical Treatment of Recurrent Endometrial Cancer: Time for a Paradigm Shift". Ann Surg Oncol. 22 (13): 4204–10. doi:10.1245/s10434-015-4504-5. PMID 25777095.CS1 maint: Multiple names: authors list (link)
16. ↑ 16.0 16.1 Kong A, Johnson N, Kitchener HC, Lawrie TA (2012). "Adjuvant radiotherapy for stage I endometrial cancer". Cochrane Database Syst Rev (4): CD003916. doi:10.1002/14651858.CD003916.pub4. PMC 4164955. PMID 22513918.CS1 maint: Multiple names: authors list (link)
17. ↑ Guillotin D, Martin SA (2014). "Exploiting DNA mismatch repair deficiency as a therapeutic strategy". Exp Cell Res. 329 (1): 110–5. doi:10.1016/j.yexcr.2014.07.004. PMID 25017099.
18. ↑ Patel B, Elguero S, Thakore S, Dahoud W, Bedaiwy M, Mesiano S (2015). "Role of nuclear progesterone receptor isoforms in uterine pathophysiology". Hum Reprod Update. 21 (2): 155–73. doi:10.1093/humupd/dmu056. PMC 4366574. PMID 25406186.CS1 maint: Multiple names: authors list (link)
19. ↑ Sylvestre VT, Dunton CJ (2010) Treatment of recurrent endometrial stromal sarcoma with letrozole: a case report and literature review. Horm Cancer 1 (2):112-5. DOI:10.1007/s12672-010-0007-9 PMID: 21761354
20. ↑ Nithin KU, Sridhar MG, Srilatha K, Habebullah S (2018). "CA 125 is a better marker to differentiate endometrial cancer and abnormal uterine bleeding". Afr Health Sci. 18 (4): 972–978. doi:10.4314/ahs.v18i4.17. PMC 6354887. PMID 30766562.CS1 maint: Multiple names: authors list (link)