Endometrial Stromal Sarcoma: Etiology, Prognosis and Treatment Options
Neoplasms, Glandular and Epithelial
Uterine sarcomas comprise 2-3% of all uterine malignancies. Tumors in this category are, in order of decreasing incidence, carcinosarcoma, leiomyosarcoma, endometrial stromal sarcoma, and adenosarcoma. Endometrial stromal sarcomas are divided into low- and high-grade according to tumor cell morphology and mitotic rate. Low-grade tumors are characterized by a slow growth pattern, presence of estrogen and/or progesterone receptors, and an indolent clinical course with late recurrences. Despite this indolent course, 37-60% of patients with early-stage disease experience recurrent disease. High-grade stromal sarcomas, on the other hand, exhibit more aggressive biological behavior and poor outcome. The standard treatment for localized endometrial stromal sarcomas is total abdominal hysterectomy and bilateral salpingo-oophorectomy. Adjuvant radiation therapy appears to reduce locoregional failure, although its benefit in terms of overall survival is unknown. Progestogens have been considered first-line therapy in recurrent low-grade tumors, with durable response rates of approximately 50%. Some authors also favor their use in the adjuvant setting, although no clear data exist to support this indication as a standard approach. Other hormonal approaches such as aromatase inhibitors may provide an alternative to progestogens in light of a more favorable toxicity profile and similar antitumor activity. Chemotherapy, including anthracyclines, is generally reserved for recurrent low-grade tumors that progress on hormonal therapies and for high-grade lesions that usually lack hormone receptors. The combination of chemotherapy and hormones may be considered in highly symptomatic patients or in those with high-volume, life-threatening disease. In summary, endometrial stromal sarcoma of the uterus is a rare disease that should be treated with radical surgery. Prognostic factors according to tumor stage, mitotic count, and tumor grade can, to some extent, predict biologic tumor behavior and prognosis. The role of postoperative radiation therapy and adjuvant progestogens, particularly for low-grade disease, remains to be defined. Recurrent or metastatic disease should be treated with systemic therapy, and the choice between hormonal therapy and chemotherapy should be based on histologic characteristics including mitotic count, cell morphology, and estrogen and progesterone receptor status. Salvage surgery and/or radiation have been associated with some long-term remissions, and can be considered as part of the multimodality approach in selected cases. New prognostic markers and specific therapeutic targets are clearly needed in this rare disease.