Endometrial cancer is a malignancy that begins in the lining of the uterus (endometrium). It is the most common gynecologic cancer in the United States and most often affects women after menopause. When detected early — as it frequently is, because abnormal bleeding prompts evaluation — endometrial cancer has an excellent prognosis, with overall five-year survival rates exceeding 80%.
Endometrial cancer develops in a hormonal and structural context that overlaps with several other gynecologic conditions. Chronic unopposed estrogen exposure — the central driver of most endometrial cancers — is also responsible for uterine fibroids and contributes to adenomyosis, conditions that can cause similar symptoms of abnormal uterine bleeding and pelvic fullness. Polycystic ovarian syndrome (PCOS) is an independent risk factor for endometrial cancer through its associated chronic anovulation and unopposed estrogen. Lynch syndrome — a hereditary mismatch repair deficiency — significantly elevates both endometrial and ovarian cancer risk and should be considered in younger patients or those with a strong family history of colorectal or gynecologic cancers.
Causes
Hormonal factors.
Approximately 80% of endometrial cancers are Type I tumors — endometrioid adenocarcinomas — that are directly driven by prolonged exposure of the uterine lining to estrogen without the balancing effect of progesterone. This "unopposed estrogen" state causes the endometrium to proliferate abnormally, progressing through a spectrum from simple hyperplasia to complex hyperplasia with atypia — a recognized precursor lesion — and ultimately to invasive carcinoma. Sources of unopposed estrogen include endogenous estrogen from adipose tissue (particularly in obese women, where peripheral conversion of androgens to estrogen is increased), exogenous estrogen-only hormone replacement therapy, tamoxifen (which acts as an estrogen agonist in the uterus despite being an estrogen antagonist in the breast), and chronic anovulation as seen in PCOS. Type II tumors — including serous and clear cell carcinomas — are less common, are not estrogen-driven, tend to occur in older and thinner women, and carry a significantly worse prognosis.
Other risk factors.
Obesity is the single strongest modifiable risk factor for endometrial cancer — women with a BMI over 40 have approximately 6 times the risk of normal-weight women, reflecting the role of adipose-derived estrogen. Type 2 diabetes and hypertension are independently associated risk factors, possibly reflecting shared metabolic pathways with obesity. Early menarche, late menopause, nulliparity, and prior pelvic radiation increase risk. Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC) is the most important hereditary risk factor and accounts for approximately 3–5% of all endometrial cancers — affected women have a 40–60% lifetime risk and require earlier and more intensive surveillance. Most sporadic cases occur in women between ages 55 and 70.
Symptoms
The most common and diagnostically important symptom is abnormal uterine bleeding — in postmenopausal women, any vaginal bleeding whatsoever is abnormal and requires prompt evaluation regardless of amount. This symptom leads to early diagnosis in the majority of cases, which explains the overall favorable prognosis of endometrial cancer compared to other gynecologic malignancies. Premenopausal women may notice unusually heavy or prolonged periods, bleeding between cycles, or unusual vaginal discharge. Pelvic pain, pressure, or a sense of fullness develop as the tumor enlarges or spreads beyond the uterus, and typically indicate more advanced disease. Weight loss and fatigue are constitutional symptoms of advanced malignancy.
Diagnosis
Evaluation begins with transvaginal ultrasound to measure endometrial thickness — a threshold of greater than 4–5 mm in postmenopausal women is the standard for further investigation. Endometrial biopsy, which can be performed in the office without anesthesia, is the definitive diagnostic test and establishes histologic type and grade.
An MRI of the pelvis is the primary imaging modality for staging endometrial cancer once the diagnosis has been confirmed by biopsy. MRI is uniquely accurate for the two staging determinations that most directly affect surgical planning: the depth of myometrial invasion — less than 50% (Stage IA) vs. 50% or greater (Stage IB) — and the presence of cervical stromal invasion (Stage II), which changes the surgical approach. The junctional zone — the dark inner myometrial layer visible on T2-weighted MRI — serves as the critical landmark for assessing invasion depth, and disruption of this layer is the key MRI finding of myometrial invasion. Diffusion-weighted imaging (DWI) improves accuracy for detecting lymph node involvement and parametrial spread. MRI also identifies ovarian or adnexal involvement and guides the decision for sentinel lymph node mapping or full lymphadenectomy. CT of the chest, abdomen, and pelvis is typically added for higher-grade tumors to assess for distant metastatic disease.
Classification (FIGO staging)
Endometrial cancer is staged using the FIGO system, which is both surgical and pathologic. MRI provides the preoperative estimate of stage that guides the surgical plan.
- Stage IA: Cancer confined to the endometrium or invading less than half the myometrial thickness. Excellent prognosis — 5-year survival above 95% for low-grade tumors.
- Stage IB: Cancer invading half or more of the myometrial thickness but still confined to the uterus. Surgery alone is often sufficient for low-grade Stage IB tumors.
- Stage II: Cancer has invaded the cervical stroma but remains confined to the uterus. Requires modified radical hysterectomy at many centers.
- Stage III: Cancer has spread beyond the uterus to the fallopian tubes, ovaries, vagina, parametrium, or regional pelvic or para-aortic lymph nodes. Adjuvant radiation and/or chemotherapy is typically required.
- Stage IV: Cancer has spread to the bladder, bowel mucosa, or distant organs including the lungs or liver. Systemic chemotherapy is the primary treatment modality.
Tumors are also graded 1–3 based on the proportion of solid non-squamous growth pattern — Grade 1 is well-differentiated and carries the best prognosis; Grade 3 is poorly differentiated and behaves more aggressively regardless of stage.
Treatments
Treatment depends on FIGO stage, tumor grade, histologic type, patient age, and fitness for surgery.
Surgery: Total hysterectomy with bilateral salpingo-oophorectomy (removal of the uterus, fallopian tubes, and ovaries) is the primary treatment for most endometrial cancers. Lymph node assessment — via sentinel lymph node mapping with indocyanine green dye or full pelvic and para-aortic lymphadenectomy — is performed simultaneously in intermediate and high-risk cases to complete surgical staging. The majority of endometrial cancer surgeries are now performed minimally invasively (laparoscopic or robotic-assisted), which reduces blood loss, hospital stay, and recovery time compared to open surgery without compromising oncologic outcomes.
Radiation therapy.
Adjuvant radiation reduces the risk of local recurrence in intermediate and high-risk tumors following surgery. Vaginal brachytherapy — delivering radiation directly to the vaginal cuff — is the most targeted option and is used for Stage IB and high-grade Stage IA tumors. External beam pelvic radiation is added when lymph node involvement or parametrial spread is present. Radiation alone can be used as primary treatment in women who are medically unfit for surgery, with curative intent in early-stage disease.
Chemotherapy and targeted therapy.
Chemotherapy with carboplatin and paclitaxel is the standard systemic regimen for advanced or high-risk histologic subtypes (serous, clear cell, carcinosarcoma). Immune checkpoint inhibitors — particularly pembrolizumab for mismatch repair-deficient (MSI-high) tumors — have transformed the treatment of advanced and recurrent endometrial cancer and are now incorporated into first-line treatment protocols. Hormonal therapy with progestins (medroxyprogesterone acetate) can be used in young women with Grade 1, Stage IA disease who wish to preserve fertility, with close endometrial surveillance during treatment.
Follow-up.
After primary treatment, clinical follow-up with pelvic examination every 3–6 months for the first 2–3 years, then annually, is standard. Imaging with MRI or CT is obtained when symptoms suggest recurrence. The vaginal cuff is the most common recurrence site and is often detected early with routine examination and brachytherapy surveillance.
Get an MRI to Confirm Your Diagnosis
Before surgical planning or starting treatment, a clear MRI diagnosis ensures the right path forward. First Look MRI offers self-pay Pelvis MRI scans — no doctor's order or insurance required — at our locations in Georgia, Texas, and Colorado.