Stage I Uterine Leiomyosarcoma
Short summary
38-year-old female was diagnosed with stage I uterine leiomyosarcoma with high mitotic count and infiltrative-type growth margins. The expert recommends to give her adjuvant chemotherapy after the surgery - 6 courses of Adriamycin + Ifosfamide chemotherapy and consider radiotherapy afterwards for local control. An alternative treatment is with the combination of Gencitabine + Taxotere. Her prognosis depends on recurrence.
Patient's questions
1. Recommended therapy
2. Alternative therapies
3. Prognosis
Medical Background
This is a 38 year-old woman diagnosed with stage I uterine leiomyosarcoma. The tumor measured 6 cm with 15 /10 HPF mitotic figures. There was no evidence of necrosis or lymph-vascular space involvement in the tumor. There was no evidence of intraperitoneal, retroperitoneal or distant metastases according to the surgical and imaging studies.
Medical opinion
Although the tumor was confined to the uterus, it is still a very malignant and aggressive tumor. Even if diagnosed at an early stage like in this case there is up to 60% chance of recurrence. Favorable prognostic factors include premenopausal status, tumor confinement within a myoma, low mitotic count and absence of necrosis. This patient is young and there was no necrosis in the tumor but there was a high mitotic count and as described there were infiltrative-type growth margins. Furthermore, if recurrence occurs, the prognosis is poor and response to chemotherapy is limited in recurrent disease.
For these reasons we usually do advocate adjuvant chemotherapy after the surgery, especially since sarcomas tend to spread via the hematogenous rout and send distant metastasis outside of the operated field. In our institution we usually administer 6 courses of Adriamycin and Ifosfamide every 3 weeks. In most of our patients that were diagnosed at an early stage we also add radiotherapy to the pelvis for local control.
It should be noted that uterine leiomysarcoma is a rare disease and the role of adjuvant chemotherapy in an early stage disease has not been defined. There is only one GOG study published in 1985 that compared adriamycin treatment to no treatment in completely resected stage I and II leiomysarcoma. Although there was no statistically significant difference in survival between the two groups, the recurrence rate was 61% in the no treatment compared to 44% in the adriamycin group. The median survival was also longer in the treatment arm. Combination chemotherapy of adriamycin and ifosfamide has better response rates compared to single agent chemotherapy although data is lacking for early stage disease.
Adjuvant irradiation increases the rate of pelvic local control but again does not increase overall survival.
Response to questions:
1. In view of the aggressive nature of the tumor in a young patient like the present one it is my belief that everything should be done in order to decrease the risk of recurrence. My advice is to give her the 6 courses of Adriamycin + Ifosfamide chemotherapy and consider radiotherapy afterwards.
2. Other alternatives are:
a. Not to give any adjuvant treatment (as long as the patient understands that she is in high risk for recurrence).
b. Offer her only radiotherapy to the pelvis for local control. This option is inferior in view of the fact that sarcomas tend to send distant metastases.
c. Recently there are several studies indicating that the combination of Gencitabine + Taxotere can achieve 53% response rate in unresectable leiomysarcoma. Considering the cardiac side effects of adriamycin, may be this regimen can also be offered to the patient although there is no data about its affectivity in early stage disease.
3. Her prognosis depends on recurrence and is difficult to expect. There is no definite data. According to different studies I would assume a 5 year-survival of 63-83%.
