Primary Treatment for Endometrial Stromal Sarcoma
The primary treatment for endometrial stromal sarcoma is total abdominal hysterectomy with bilateral salpingo-oophorectomy, due to the hormonal sensitivity of these tumors. 1, 2
Surgical Management
Total abdominal hysterectomy (TAH) with bilateral salpingo-oophorectomy (BSO) is the definitive standard surgical approach for all stages of endometrial stromal sarcoma. 1, 2 This differs from other uterine sarcomas where BSO remains controversial—for endometrial stromal sarcoma, removing the ovaries is essential because these tumors are hormone-sensitive and estrogen exposure drives disease progression. 1
What NOT to Do Surgically
Lymphadenectomy is NOT routinely indicated for endometrial stromal sarcoma, as lymph node involvement occurs in less than 5% of cases. 2, 3 While older guidelines suggested lymphadenectomy might be an option given possible nodal involvement 1, the most recent evidence from 2025 clearly states it is not indicated. 2
Do NOT perform lymphadenectomy unless there is macroscopic nodal involvement. 1
Critical Post-Operative Restrictions
Patients must NOT receive hormone replacement therapy containing estrogens after surgery. 1, 2 This is an absolute contraindication because estrogen stimulates tumor growth in endometrial stromal sarcoma. 1
Tamoxifen is also contraindicated as it can have pro-estrogenic effects in these patients. 1, 2
Adjuvant Therapy for Localized Disease
Adjuvant pelvic radiotherapy is NOT routinely indicated for early-stage (FIGO stage I-II) endometrial stromal sarcoma because it has not been shown to improve survival or relapse-free survival. 1, 2 While retrospective studies suggested possible decreases in local relapses, a randomized trial failed to demonstrate survival benefit. 1
Adjuvant estrogen deprivation therapy is NOT indicated for early-stage disease. 2 Reserve hormonal therapy for advanced or metastatic disease only.
Treatment for Advanced/Metastatic Disease
For patients with advanced or metastatic endometrial stromal sarcoma, the treatment exploits their hormonal sensitivity through estrogen deprivation therapy. 1, 2
Hormonal Therapy Options (in order of use):
- Aromatase inhibitors (preferred for metastatic disease) 2
- Progestins (medroxyprogesterone acetate or megestrol) 1, 4
- GnRH analogues (for premenopausal patients) 1
These hormonal therapies achieve response rates of approximately 46% with an additional 46% achieving disease stabilization. 5
Surgical resection of isolated lung metastases is an option given the indolent natural history of endometrial stromal sarcoma. 1 These tumors have a tendency for late pulmonary recurrence that may be amenable to surgical resection.
Special Considerations
High-Grade Endometrial Stromal Sarcoma vs. Low-Grade
The treatment paradigm described above applies to low-grade endometrial stromal sarcoma (the classic form). 1
For high-grade endometrial stromal sarcoma and undifferentiated endometrial sarcoma, the treatment parallels that for adult-type soft tissue sarcomas rather than hormonal therapy, as these tumors are not hormone-sensitive. 1 These require chemotherapy regimens such as doxorubicin-based therapy or gemcitabine-docetaxel. 6, 7
Incidental Discovery
If endometrial stromal sarcoma is discovered incidentally after myomectomy or other uterine-sparing surgery, completion hysterectomy with bilateral salpingo-oophorectomy is recommended. 7
Follow-Up Protocol
High-grade sarcoma patients should be followed every 3-4 months in the first 2-3 years, then twice yearly up to year 5, then annually thereafter. 1 Regular chest imaging (X-ray or CT) is essential to detect pulmonary metastases, which are often asymptomatic when resectable. 1
For low-grade endometrial stromal sarcoma, follow-up can be every 4-6 months with chest imaging at more relaxed intervals in the first 3-5 years, then yearly. 1 These patients require prolonged surveillance as recurrences can occur late, with a median time to recurrence of approximately 34 months. 5
Common Pitfalls to Avoid
- Never prescribe estrogen-containing hormone replacement therapy—this is the most critical error to avoid as it will stimulate tumor growth. 1, 2
- Do not use tamoxifen for any indication in these patients. 1, 2
- Do not routinely perform lymphadenectomy—it adds morbidity without benefit in the absence of visible nodal disease. 2, 3
- Do not confuse low-grade with high-grade endometrial stromal sarcoma—they require completely different systemic treatment approaches (hormonal vs. chemotherapy). 1, 6