What is the management of grade 1 (Endometrial Cancer)?

Management of Grade 1 Endometrial Cancer

For grade 1 endometrial cancer, total hysterectomy with bilateral salpingo-oophorectomy is the definitive treatment, with adjuvant therapy decisions based entirely on surgical staging and specific risk factors—most low-risk patients (stage IA/IB, grade 1, endometrioid histology) require no adjuvant therapy after surgery. 1

Primary Surgical Management

All patients with grade 1 endometrial cancer should undergo comprehensive surgical staging as the cornerstone of treatment. 1

The minimal surgical procedure must include:

• Total hysterectomy with bilateral salpingo-oophorectomy 1
• Peritoneal fluid or washings for cytology 1
• Thorough exploration of the abdominal cavity, pelvic and para-aortic nodal areas 1
• Pelvic and para-aortic lymph node assessment (though the survival benefit of routine lymphadenectomy remains unclear, it provides critical staging information) 1, 2

The pathologic evaluation must document: depth of myometrial invasion, cervical involvement, tumor size and location, lymphovascular space invasion, and nodal status when resected. 1

Risk Stratification After Surgery

Grade 1 endometrial cancer patients are stratified into risk categories that determine adjuvant therapy:

Low-Risk Disease (Stage IA/IB, Grade 1, Endometrioid Histology)

No adjuvant therapy is required—observation alone is the standard of care. 1, 2

This applies specifically to:

• Stage IA or IB disease 1
• Grade 1 endometrioid histology 1
• Less than 50% myometrial invasion 2
• No lymphovascular space invasion 2

Intermediate-Risk Disease

If grade 1 disease has additional risk factors (age ≥60 years, deeper myometrial invasion, or lymphovascular space invasion), vaginal brachytherapy alone is the preferred adjuvant treatment. 2, 3

Pelvic radiotherapy significantly reduces pelvic/vaginal relapses but does not improve overall survival, so it should be reserved for patients with multiple intermediate-risk factors. 1

Stage II Disease (Cervical Involvement)

• Stage IIA (endocervical glandular involvement only): Vaginal brachytherapy if myometrial invasion is <50% 2
• Stage IIB (cervical stromal invasion): External pelvic radiotherapy with brachytherapy boost 2

Fertility-Sparing Treatment (Exceptional Circumstances Only)

Fertility-sparing treatment with high-dose progestins is NOT standard of care but may be considered in highly selected young patients who meet ALL of the following criteria: 1, 4, 5

• Well-differentiated (grade 1) endometrioid adenocarcinoma confirmed by expert pathology review 1
• Disease limited to the endometrium on MRI (preferred) or transvaginal ultrasound 1
• No myometrial invasion 1, 4
• Absence of suspicious or metastatic disease on imaging 1
• Strong desire for fertility preservation 1, 4

The treatment regimen consists of:

• Medroxyprogesterone acetate 500-600 mg daily OR megestrol acetate 160 mg daily 6, 7, 4, 5
• Re-evaluation with dilation and curettage at 3 months 4
• Median time to response is 12 weeks (range 4-60 weeks) 5
• 76% of patients respond to treatment, but 24% of responders will recur (median time to recurrence 19 months) 5

Critical caveats for fertility-sparing treatment:

• Patients must undergo extensive counseling that this approach is NOT standard of care 1
• There is a documented risk of concurrent or subsequent ovarian cancer, even in young patients 8
• Hysterectomy with bilateral salpingo-oophorectomy should be performed after childbearing is complete 4
• Close surveillance every 3-6 months is mandatory 1, 4

Advanced Disease (Stage III-IV)

For the rare grade 1 tumor that presents at advanced stage:

• Optimal surgical debulking remains the initial approach 2
• Combination chemotherapy with cisplatin and doxorubicin OR carboplatin and paclitaxel significantly improves progression-free and overall survival compared to radiation alone 1, 2
• External radiotherapy with or without brachytherapy may be added 2

Common Pitfalls to Avoid

Do not assume all grade 1 tumors are low-risk—surgical staging is essential because grade alone does not determine prognosis. 1

Do not offer fertility-sparing treatment without MRI confirmation of disease limited to endometrium—myometrial invasion is an absolute contraindication. 1, 4

Do not preserve ovaries in young women undergoing fertility-sparing treatment without extensive genetic counseling—there is documented risk of synchronous or metachronous ovarian cancer. 8

Notable nuclear atypia raises the grade by one—a grade 1 tumor with significant nuclear atypia should be treated as grade 2. 1