Uterine Cancer
Epidemiology and Etiology
Uterine cancer is the most common gynecologic cancer in the US, with an increasing incidence estimated to account for 65,620 new cases and 12,590 deaths in 2020.1 Risk factors include obesity, early menarche, late menopause, nulliparity, diabetes mellitus, use of tamoxifen, and hereditary disorders such as Lynch syndrome.
The risk is reduced with parity and the use of oral contraceptives. Most patients are perimenopausal or postmenopausal.Pathology
Approximately 95% of uterine tumors arise in the lining of the uterus and are termed endometrial carcinomas. Endometrial carcinomas may be subdivided into endometrioid and nonendometrioid, with the former accounting for approximately 80% of cases and related to relative estrogen excess, whereas the latter are hormone-independent and usually occur in older postmenopausal women. Nonendometrioid endometrial carcinoma includes serous carcinoma, clear-cell carcinoma, and carcinosarcoma. Nonendometrial uterine tumors may include sarcomas and lymphomas.
Clinical Presentation
The most common presentation is vaginal bleeding, usually occurring in postmenopausal women. Of note, the severity of the bleeding does not correlate with the risk of malignancy.
Diagnostic Testing
Premenopausal women with irregular vaginal bleeding and risk factors for endometrial cancer and all postmenopausal women with any vaginal bleeding should be evaluated for endometrial cancer with pelvic examination, transvaginal ultrasound, and endometrial biopsy. Patients with endometrial thickness less than 4 mm on transvaginal ultrasound may not need endometrial biopsy in the absence of additional bleeding episodes.
Staging
The TNM and FIGO staging systems are both used in uterine cancer. In general, FIGO stage I is similar to T1 disease, with tumor confined to the uterus.
FIGO stage II is similar to T2 disease, with tumor invading the cervix but not otherwise extending beyond the uterus. FIGO stage IIIA/B is similar to T3 disease, with tumor involving serosa, adnexa, vagina, or parametrium. FIGO stage IIIC is similar to N1-2 disease. FIGO stage IVA is similar to T4 disease, with tumor involving bladder or bowel. FIGO stage IVB is similar to M1 disease, with distant metastatic disease.TREATMENT
• The primary treatment modality is surgery with additional therapy depending on the surgical staging. Patients with stage IA (limited to the endometrium or invading less than half of the myometrium) usually do not require additional therapy, although select patients with higher risk disease may be treated with vaginal brachytherapy. Patients with surgically staged IB-IV disease are treated with radiation therapy, primarily vaginal brachytherapy in stage IB and external beam radiation in stages II to IV (with or without the addition of brachytherapy). Patients with stage III or IV disease should also receive systemic therapy.
• The most commonly used chemotherapy regimen carboplatin plus paclitaxel. Trastuzumab may be added to chemotherapy in patients with HER2+ tumors. Patients with ER+ tumors and an indolent course may be treated with endocrine therapy, such as AIs or tamoxifen. Additional treatment options may include pembrolizumab with or without lenvatinib, as well as several other chemotherapeutic and/or targeted agents.27