para>This malignancy is not associated with pregnancy.
EPIDEMIOLOGY
Incidence
- Endometrial cancer is the most common gynecologic malignancy; fourth most common cancer in women and eighth leading cause of cancer-related death in women worldwide.
- In the United States, it is estimated that endometrial cancer will account for 54,870 new cases and 10,170 deaths in 2015 (2)[C].
Prevalence
500,000 women in the United States
ETIOLOGY AND PATHOPHYSIOLOGY
Continuous estrogen stimulation unopposed by progesterone
- Endometrial: unopposed estrogen
- Estrogen replacement therapy without concomitant progesterone increases the risk. Addition of progesterone decreases risk to that of general population.
- Sarcomas: etiology unknown
Genetics
- Endometrial: Lynch syndrome (hereditary nonpolyposis colorectal cancer)
- Sarcoma: African American, higher incidence of leiomyosarcoma, childhood retinoblastoma survivors
RISK FACTORS
- Early menarche/late menopause
- Nulliparity
- Personal or family history of colon or reproductive system cancer
- Obesity
- Diabetes mellitus
- Hypertension
- Polycystic ovarian syndrome
- Estrogen-secreting tumor
- Endometrial hyperplasia
- Unopposed estrogens
- Tamoxifen use
- Increasing age
GENERAL PREVENTION
- In young women who are obese or anovulatory, the risk of endometrial cancer can be reduced by taking oral contraceptive pills, permanently losing weight, or taking cyclic progesterone to prevent unopposed estrogen's effects on the uterus (3)[A].
- Estrogen replacement therapy should always include progesterone unless the woman has had a hysterectomy (3)[A].
- Cigarette smoking has been associated with a lower risk of type I endometrial cancer; however, it is not recommended secondary to its many health risks and increase risk of type II endometrial cancer.
COMMONLY ASSOCIATED CONDITIONS
- Endometrial hyperplasia: 1-25% will progress to endometrial adenocarcinoma:
- Simple without atypia
- Complex without atypia
- Simple with atypia
- Complex with atypia
- 43% with complex hyperplasia with atypia have concurrent endometrial cancer.
- Endometrial cancer patients should be screened regularly for breast and colon cancer because of an increased risk of these cancers.
- Patients who have breast or colon cancer are at increased risk for endometrial cancer.
- Granulosa cell tumors of the ovary produce estrogen; these patients will have an increased risk of endometrial cancer.
DIAGNOSIS
HISTORY
- Endometrial cancer
- Postmenopausal bleeding is the most frequent sign. Any spotting or abnormal discharge mandates evaluation.
- Premenopausal patients with history of anovulation and heavy, irregular, or prolonged periods that fail multiple medical managements mandate evaluation.
- Sarcoma
- Mixed m ¼llerian sarcoma: bleeding and prolapsing tissue, pain (2)[C]
- Leiomyosarcoma: pelvic pain, pressure, uterine mass, abnormal bleeding
PHYSICAL EXAM
Pelvic exam: enlarged, fixed
DIFFERENTIAL DIAGNOSIS
- Atypical complex hyperplasia: a premalignant lesion of the endometrium
- Cervical cancer
- Ovarian cancer invading the uterus
- Endometriosis
- Adenomyosis
- Leiomyoma
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Liver and renal function tests
- Transvaginal ultrasound usually shows increased endometrial thickness (>4 mm in postmenopausal patients or in patients with irregular or heavy periods if >35 years of age). (1)[A]
- Levels of cancer antigen 125 (CA-125) may be elevated when intra-abdominal disease is present (1)[A].
- Chest x-ray (CXR): Most common site of metastases is the lungs.
- Mammogram and colonoscopy: Endometrial cancer is associated with breast and colon cancer.
Follow-Up Tests & Special Considerations
- Endometrial Cancer is mostly localized to the uterus, therefore preop evaluation for metastasis is not needed unless metastasis is already suspected.(2)[A]
- CT scan, PET/CT, MRI, CA-125: not part of the routine evaluation but may be needed if metastasis is suspected; patient is a poor operative candidate or pathology returns high grade (G3 endometroid, papillary serous, clear cell, carcinosarcoma) (2)
- MRI has been reported to show the depth of myometrial penetration accurately but is not always cost-effective. (4)[A]
Diagnostic Procedures/Other
- Office endometrial biopsy (90% accurate): If negative with high suspicion for cancer or patient continues to have bleeding, a dilation and curettage (D&C) is necessary. (2)[B] Endometrial stromal sarcoma and leiomyosarcoma rarely are diagnosed preoperatively. Any patient with history of irregular, heavy, or prolonged periods should undergo endometrial biopsy prior to endometrial ablation procedures.
- Fractional D&C is 99% accurate except in cases of sarcoma.
- If surgical approach is favored, D&C with hysteroscopic guidance is recommended over D&C alone, due to its ability to pick up discrete lesions. (2)[A]
Test Interpretation
- Federation of Gynecology and Obstetrics Staging System: revised 2009
- Stage I (confined to corpus uteri)
- A: no or <1/2 myometrial invasion
- B: invasion ≥1/2 the myometrium
- Stage II: Tumor invades cervical stroma but does not extend beyond the uterus.
- Stage III: local and/or regional spread
- A: uterine serosal and/or adnexal invasion
- B: vaginal and/or parametrial involvement
- C: metastases to pelvic and/or para-aortic lymph nodes
- IIIC1: +pelvic nodes
- IIIC2: +para-aortic lymph nodes positive pelvic lymph nodes
- Stage IV: Tumor invades bladder and/or bowel mucosa and/or distant metastases:
- A: Tumor invades bladder and/or bowel mucosa.
- B: distant metastases, including intra-abdominal metastases and/or inguinal lymph nodes (1)[A]
- Uterine sarcoma criteria for diagnosis: mitotic index, cellular atypia, and areas of coagulative necrosis separated from tumor (5)[C]
TREATMENT
GENERAL MEASURES
- Main treatment for uterine cancer is surgery.
- Radiation is used to prevent tumor recurrence at the vaginal cuff.
MEDICATION
First Line
- Endometrial
- Chemotherapy for advanced or recurrent disease incurable with surgery and radiation
- Paclitaxel + carboplatin (2)[B]
- Doxorubicin + cisplatin + paclitaxel
- Hormonal therapy
- Medroxyprogesterone acetate: for recurrence or metastases
- Megestrol (Megace) 160 mg/day for at least 2 months for women with premalignant lesions, atypical complex hyperplasia, or well-differentiated endometrial cancer in patients desiring fertility. Follow with D&C to determine cancer resolution.
- Levonorgestrel-containing intrauterine device: as mentioned earlier for patients who desire future fertility (3,6,7)[A]
- Sarcoma
- Chemotherapy
- Doxorubicin as single agent or in combination (5)[A]
- Hormonal
- Tamoxifen or aromatase inhibitors; not fully studied
- Progesterones (3)[A]
ADDITIONAL THERAPIES
Radiation therapy
- Nonoperative candidates: radiation therapy alone
- Low risk: no adjuvant radiation therapy
- Intermediate risk: Consider adjuvant vaginal brachytherapy; reduces local recurrences but has no effect on overall survival
- High risk: chemotherapy and radiation therapy in some cases (4,8)[A]
SURGERY/OTHER PROCEDURES
Surgical staging
- Extrafascial hysterectomy and bilateral salpingo-oophorectomy
- Cytologic washings
- Pelvic and para-aortic lymph node dissection
- Omental sampling, as indicated
- Optimal tumor debulking (1)[A]
Geriatric Considerations
Older (and obese) patients may be at high risk for surgery. Alternative radiation therapy can be considered.
INPATIENT CONSIDERATIONS
Admission-Criteria/Initial Stabilization
- Excessive vaginal bleeding
- Preoperative stabilization
Nursing
Routine; ensure postoperative pain is controlled.
Discharge Criteria
Postsurgical criteria: pain controlled, tolerating diet, ambulating, and voiding
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Follow up visit with Speculum and rectovaginal exam every 3 to 6 months for 2 years, then every 6 months for 3 years, and then annually for life (2)[C]
PATIENT MONITORING
- Annual CXR is no longer recommended.
- CT scan or PET/CT scan of the chest, abdomen, and pelvis should be used only to investigate suspicion of recurrent disease, not routinely
DIET
As tolerated and according to comorbidities
PATIENT EDUCATION
After surgery:
- No intercourse for ~6 weeks
- No lifting >10 to 15 lb
- No driving until pain free
- Do not expect resumption of full activity for 6 weeks.
PROGNOSIS
5-year survival rates
COMPLICATIONS
- Surgical: excessive bleeding, wound infection, lymphedema, deep vein thrombosis (DVT), and damage to the urinary or intestinal systems
- Radiation: diarrhea, ileus, bowel obstruction or fistula, radiation cystitis, proctitis, vaginal stenosis, DVT
- Chemotherapy: per the drug given
REFERENCES
11 Creasman W. Revised FIGO staging for carcinoma of the endometrium. Int J Gynaecol Obstet. 2009;105(2):109.22 American College of Obstetricians and Gynecologists. ACOG practice bulletin, clinical management guidelines for obstetrician-gynecologists, number 149, April 2015: endometrial cancer. Obstet Gynecol. 2015;125(4):1006-1026.33 Polyzos NP, Pavlidis N, Paraskevaidis E, et al. Randomized evidence on chemotherapy and hormonal therapy regimens for advanced endometrial cancer: an overview of survival data. Eur J Cancer. 2006;42(3):319-326.44 Humber C, Tierney J, Symonds P, et al. Chemotherapy for advanced, recurrent or metastatic endometrial carcinoma. Cochrane Database Syst Rev. 2005;(4):CD003915.55 Gadducci A, Cosio S, Romanini A, et al. The management of patients with uterine sarcoma: a debated clinical challenge. Crit Rev Oncol Hematol. 2008;65(2):129-142.66 Bramwell VH, Anderson D, Charette ML. Doxorubicin-based chemotherapy for the palliative treatment of adult patients with locally advanced or metastatic soft tissue sarcoma. Cochrane Database Syst Rev. 2003;(3):CD003293.77 Fleming GF, Brunetto VL, Cella D, et al. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2004;22(11):2159-2166.88 Einhorn N, Trop © C, Ridderheim M, et al. A systematic overview of radiation therapy effects in uterine cancer (corpus uteri). Acta Oncol. 2003;42(5-6):557-561.
SEE ALSO
- Cervical Malignancy
- Algorithm: Pelvic Pain
CODES
ICD10
- C54.1 Malignant neoplasm of endometrium
- C55 Malignant neoplasm of uterus, part unspecified
- C54.2 Malignant neoplasm of myometrium
- C54.9 Malignant neoplasm of corpus uteri, unspecified
- C54.3 Malignant neoplasm of fundus uteri
- C54.8 Malignant neoplasm of overlapping sites of corpus uteri
- C54.0 Malignant neoplasm of isthmus uteri
ICD9
- 182.0 Malignant neoplasm of corpus uteri, except isthmus
- 179 Malignant neoplasm of uterus, part unspecified
- 182.8 Malignant neoplasm of other specified sites of body of uterus
- 182.1 Malignant neoplasm of isthmus
SNOMED
- 188192002 Malignant neoplasm of endometrium of corpus uteri (disorder)
- 254877001 sarcoma of uterus (disorder)
- 447389009 Leiomyosarcoma of uterus (disorder)
- 447266004 Sarcoma of endometrium (disorder)
CLINICAL PEARLS
- Most common presenting symptom is abnormal uterine bleeding.
- Any patient with history of irregular, heavy, or prolonged periods should undergo endometrial biopsy.
- Primary cause is unopposed estrogen.
- Endometrial thickness on transvaginal ultrasound of <5 mm makes endometrial cancer very unlikely.
- Primary treatment is with surgery, with possible chemotherapy ± radiation.