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Low Mitotic Count Is an Independent Predictor of Survival in Women With Recurrent Uterine Leiomyosarcoma

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Key Points

  • A retrospective study of 115 women with recurrent or persistent uterine leiomyosarcoma was conducted to identify prognostic factors that may influence outcomes in this patient population.
  • Although low number of mitoses at the time of diagnosis, time to relapse, and surgical treatment were found to affect the 5-year survival rate post relapse, only low mitotic count was an independent predictor of overall survival.
  • These study findings may shed some light on identifying patients who may be spared toxic therapeutic options that have little chance of substantial clinical benefit.

Although low mitotic count, surgery, and disease-free interval of more than 6 months were associated with improved survival in women with recurrent or persistent uterine leiomyosarcoma, only low number of mitoses was identified as an independent predictor of survival post relapse, according to study findings presented by Rauh-Hain et al in the International Journal of Gynecological Cancer. Further studies in a homogeneously treated group of patients are required before using these parameters to predict survival, guide treatment decisions, and craft appropriate clinical trial designs, the investigators noted.

Although uterine leiomyosarcoma is a rare malignancy, it is well known for its aggressive nature. About half of women with this type of uterine cancer will present with disease confined to the uterus, but many patients will experience disease recurrence. The prognosis is generally poor for patients with recurrent or persistent uterine leiomyosarcoma.

Treatment choices for these women depend on previous therapy, the site of and time to tumor recurrence, as well as performance status. With no specific risk-stratification tool available at the time of tumor recurrence, the investigators performed a retrospective study intended to identify prognostic factors that may influence outcomes in women with recurrent or persistent uterine leiomyosarcoma.

Study Details

From the pathology archives and tumor registry database of three participating institutions, 115 patients with recurrent (75) or persistent (40) uterine leiomyosarcoma were identified. Between January 1, 2000, and December 31, 2010, these women had received treatment for their uterine cancer consisting of chemotherapy, radiotherapy, and/or surgery if accessible. The investigators reviewed the clinical records of these women for demographics, treatment, and outcome parameters.

The median age at diagnosis was 56 years (range = 41–83 years). Approximately 40% of these women had stage I disease initially, and 40% had stage IV disease initially. More than 90% of these tumors were grade 3. Forty-one women (36%) underwent no initial adjuvant therapy. Treatment at the time of tumor recurrence included chemotherapy (57%), chemotherapy plus radiotherapy (26%), and surgery (47%).

In this study, the disease-free interval was defined as the time from the end of primary therapy until a proven tumor recurrence. Computed tomography findings and histopathologic confirmation were used to diagnose tumor recurrence, which was classified as vaginal/pelvic, abdominal, lung, or distant (central nervous system, bone, or extra-abdominal lymph nodes). Among the sites of relapse or persistent disease, about 60% were in the lungs; between 40% and 44% were in the vagina, pelvis, or abdomen; and 48% were in multiple sites.

Women With a Low Mitotic Count Fared Better Post Relapse

At a median follow-up of 24.9 months, 23% of the patients were alive. The investigators reported a 5-year survival rate of 15% post relapse, which did not significantly differ between women with recurrent or persistent disease (16% vs 13%, P = .1).

Certain variables were found to affect survival, whereas others did not. On univariate analysis, the factors identified as affecting the 5-year survival rate post relapse were low number of mitoses at the time of diagnosis (< 25, 25% vs 5%, P = .002), time to relapse from original diagnosis (≤ 6 vs > 6 months, 8% vs 22%, P = .003), and surgical treatment (17% vs 12%, P = .01). However, on multivariate analysis, the only independent predictor of overall survival post relapse was low number of mitoses at initial presentation (hazard ratio = 0.5, 95% confidence interval = 0.3–0.8, P = .02).

In contrast, the factors that were not associated with survival were age at diagnosis, stage of tumor at diagnosis, chemotherapy at the time of original diagnosis, chemotherapy at the time of relapse, site of tumor recurrence, and single vs multiple sites of tumor recurrence.

Closing Thoughts

There is limited information available regarding prognostic factors at the time of recurrence of uterine leiomyosarcoma, and the influence of mitotic count on prognosis has been a controversial topic. However, these study findings, which reportedly reflect one of the largest retrospective series of patients with recurrent or persistent uterine leiomyosarcoma, may shed some light on identifying those patients who may be spared toxic therapeutic options that have little chance of substantial clinical benefit.

“Although this is a retrospective analysis, the data presented are especially valuable, as they reflect relatively recent management practice for this disease, with this large group of patients all treated within a 10-year period,” concluded the investigators.

Marcela G. del Carmen, MD, MPH, of the Division of Gynecologic Oncology, Vincent Obstetrics and Gynecology, Massachusetts General Hospital, Boston, is the corresponding author of this article in the International Journal of Gynecological Cancer.

The authors reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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