Adjuvant Management of Uterine Leiomyosarcoma
Illustrative Case Series
Adjuvant Management of Uterine Leiomyosarcoma
A 78-year-old female had been generally well with no known chronic medical conditions and was taking no medications when she presented to her primary care physician with lower abdominal pain and urinary frequency of one month's duration. Physical examination at the time revealed a well-appearing woman with normal vital signs and no abnormal physical findings except a palpably enlarged uterus by bimanual pelvic examination. CT scan confirmed the presence of a uterine mass suspicious for malignancy. She was referred to a gynecologic oncologist and had a total abdominal hysterectomy and salpingo-oophorectomy with partial infracolic omentectomy and pelvic debulking of what appeared to be a large (15 cm) tumor mass. Final pathology was high-grade leiomyosarcoma with microscopic invasion of the colon and bladder.
Following an uneventful postoperative course and just prior to hospital discharge, an oncology opinion is requested regarding recommendations for additional management. The gynecologic oncologist noted that although all gross tumor was resected, he remained suspicious of residual microscopic disease.
At the time of consultation, the patient appears better than what might be expected. There is slight pallor, but vital signs were normal, and for the most part, she was free of pain and ambulating without assistance. Cardiac and pulmonary examinations were normal. Laboratory studies revealed her hemoglobin to be 10.4 g/dL and her white blood count was 12,800 per cu mm. Serum electrolytes, creatinine, and liver function tests were all within normal limits. The patient lives with her family and has an excellent network of support within the nearby community.
Discussion
In general, uterine sarcomas are minimally sensitive to chemotherapy and the role for adjuvant systemic treatment has not been established. Nonetheless, leimyosarcomas are particularly aggressive with very high recurrence rates both locally and at distant sites.1,2 It appears the risk of recurrence at distant sites relates directly with the size of the primary tumor.3
In an effort to reduce local recurrence, various radiation approaches have been examined,4-7 but to date there has been no clearly demonstrated improvement in survival. In fact, in an EORTC trial, adjuvant RT was disappointing in that treatment resulted in neither improved survival nor local control.8 Thus, it remains unclear whether adjuvant radiation is of value for patients with leiomyosarcoma; typically, it is reserved for patients with high likelihood of local recurrence, such as those with large primary tumors.
There is, however, stronger rationale for adjuvant systemic therapy based on the high rate of recurrence at distant sites. A number of observational studies suggest that single agents or combinations thereof afford some improvement in overall survival,9,10 whereas others have suggested no benefit.11 In one prospective trial of gemcitabine and docetaxel administered to 25 patients with high-grade uterine leiomyosarcoma (stages I-IV), there was a 2-year progression-free survival rate of 40%,12 a rate comparing favorably to historic controls and providing rationale for further investigation of this combination or others in the adjuvant setting.
Recommendations
Although the current patient is 78 years old, she previously had been healthy and remained physiologically intact throughout recent major surgery. The tumor resected was large, high-grade, and with demonstrable invasion into surrounding tissue including colon and bladder. It would appear the chance of local and or distant recurrence would be close to 100%. With this in mind, my recommendation would be to undertake a course of adjuvant radiation followed by systemic chemotherapy. Depending on performance status after radiation, I would either recommend gemcitabine alone or in combination with docetaxel. In light of the lack of strong evidence for this approach, it also would be perfectly reasonable to suggest supportive care alone, acknowledging the very high likelihood of recurrence with or without treatment and thereby avoiding the possible treatment associated toxicity. As always, I would look to the patient and family for guidance, formulating a final treatment plan based upon informed goals and expectations.
References
1. Abeler VM, et al. Uterine sarcomas in Norway. A histopathological and prognostic survey of a total population from 1970 to 2000 including 419 patients. Histopathology 2009;54:355-364.
2. Major FJ, et al. Prognostic factors in early-stage uterine sarcoma. A Gynecologic Oncology Group study. Cancer 1993;71:1702-1709.
3. Giuntoli RL, 2nd, et al. Retrospective review of 208 patients with leiomyosarcoma of the uterus: Prognostic indicators, surgical management, and adjuvant therapy. Gynecol Oncol 2003;89:460-469.
4. Chauveinc L, et al. Uterine sarcomas: The Curie Institut experience. Prognosis factors and adjuvant treatments. Gynecol Oncol 1999;72:232-237.
5. Gadducci A, et al. Uterine leiomyosarcoma: Analysis of treatment failures and survival. Gynecol Oncol 1996;62:25-32.
6. Sorbe B. Radiotherapy and/or chemotherapy as adjuvant treatment of uterine sarcomas. Gynecol Oncol 1985;20:281-289.
7. Vongtama V, et al. Treatment, results and prognostic factors in stage I and II sarcomas of the corpus uteri. AJR Am J Roentgenol 1976;126:139-147.
8. Ferrer F, et al. Impact of radiotherapy on local control and survival in uterine sarcomas: A retrospective study from the Grup Oncologic Catala-Occita. Int J Radiat Oncol Biol Phys 1999;44:47-52.
9. Odunsi K, et al. Efficacy of adjuvant CYVADIC chemotherapy in early-stage uterine sarcomas: Results of long-term follow-up. Int J Gynecol Cancer 2004;14:659-664.
10. Riddle PJ, et al. Retrospective study of management of uterine sarcomas at Oxford 1990-1998: Role of adjuvant treatment. Clin Oncol (R Coll Radiol) 2002;14:54-61.
11. Benoit L, et al. The role of surgery and treatment trends in uterine sarcoma. Eur J Surg Oncol 2005;31:434-442.
12. Hensley ML, et al. Adjuvant gemcitabine plus docetaxel for completely resected stages I-IV high grade uterine leiomyosarcoma: Results of a prospective study. Gynecol Oncol 2009;112:563-567.
A 78-year-old female had been generally well with no known chronic medical conditions and was taking no medications when she presented to her primary care physician with lower abdominal pain and urinary frequency of one month's duration. Physical examination at the time revealed a well-appearing woman with normal vital signs and no abnormal physical findings except a palpably enlarged uterus by bimanual pelvic examination. CT scan confirmed the presence of a uterine mass suspicious for malignancy. She was referred to a gynecologic oncologist and had a total abdominal hysterectomy and salpingo-oophorectomy with partial infracolic omentectomy and pelvic debulking of what appeared to be a large (15 cm) tumor mass. Final pathology was high-grade leiomyosarcoma with microscopic invasion of the colon and bladder.Subscribe Now for Access
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