General Medical Information

Uterine Cancer Treatment

Neville F. Hacker

Surgery
The only treatment of any proven curative value for the frankly malignant uterine sarcomas is surgical excision. This typically involves total abdominal hysterectomy and bilateral salpingo-oophorectomy, although in young patients it may be reasonable to preserve the ovaries in a patient with a leiomyosarcoma, particularly if the tumor has arisen in a fibroid (186). Lissoni et al. (187) reported eight young patients with a diagnosis of leiomyosarcoma after myomectomy who were followed conservatively. All were nulliparous and all had no evidence of disease on ultrasonography, hysteroscopy, chest radiography, and pelvic and abdominal CT scan or MRI. The mean mitotic count of the leiomyosarcomas was 6 per 10 HPF, with a range of 5 to 33. With a median follow-up of 42 months, three live births were recorded, but one patient recurred and died. Surgical staging offers prognostic information, but there is no evidence that the information can be used to improve survival.

Radiation Therapy
Although the value of adjuvant radiation is controversial, most authors suggest that it improves tumor control in the pelvis without influencing final outcome. These findings are based on clinical staging and would be expected because of the high incidence of disease beyond the uterus at the time of laparotomy.

Two reports suggest that for patients with surgical stage I or II disease, pelvic radiation does improve survival. A report from Vienna suggested that pelvic radiation for all uterine sarcomas was an effective treatment with regard to disease-specific survival in patients with early-stage disease, and increased local control even in patients with advanced disease). A retrospective review of 43 patients with mixed mullerian tumors from Vanderbilt University revealed a significant survival advantage for patients with surgical stage I or II disease treated with surgery plus pelvic irradiation. This report noted that 29% of patients with clinical stage I or II disease were upstaged at laparotomy.

It is not known whether extended-field or whole-abdomen radiation after surgical staging can influence prognosis, although whole-abdomen radiation has been reported to prevent abdominal relapse.

Chemotherapy
A number of chemotherapeutic agents are active against uterine sarcomas, but a large study of 1,042 patients with uterine sarcomas reported to the Cancer Registry of Norway from 1956 to 1992 reported no change in 5-year survival rate after the introduction of chemotherapy into the treatment protocols.

The most important drugs are doxorubicin, cisplatin, and ifosfamide. Unfortunately, most responses are partial and of short duration. For cisplatin (50 mg/m2 every 3 weeks), the GOG reported a complete response rate of 8% and a partial response rate of 11% among 63 patients with advanced or recurrent mixed mesodermal tumors who had received no prior chemotherapy. Among 33 patients with leiomyosarcomas, there was only 1 partial response (3%)By contrast, leiomyosarcomas appear to be more responsive to doxorubicin. In the GOG trials, the response rate for leiomyosarcomas was 25% (7 of 28), compared with 10% (4 of 41) for mixed mesodermal sarcomas. Ifosfamide also has good activity against mixed mesodermal sarcomas, the GOG demonstrating 9 responses among 28 patients (31.2%). For leiomyosarcomas, the response rate for ifosfamide was 17.2% (6 of 35), and all responses were partial.

Peters et al. treated 11 patients with advanced or recurrent uterine stromal sarcomas or mixed mesodermal tumors with cisplatin 100 mg/m2 and doxorubicin 40 to 60 mg/m2 every 3 to 4 weeks for six cycles and reported a response in eight patients (73%). Three patients had a negative second-look procedure and two were alive and free of disease for more than 24 months.

Because of the propensity for early hematogenous spread, adjuvant chemotherapy after hysterectomy to eliminate micrometastases is an attractive concept. However, in a randomized GOG study of doxorubicin after total abdominal hysterectomy and bilateral salpingo-oophorectomy for stage I or II uterine sarcoma, neither survival nor progression-free interval was prolonged by the adjuvant chemotherapy. In a nonrandomized study, Peters et al. reported 17 patients with high-risk clinical stage I uterine stromal sarcomas or mixed mesodermal tumors who were treated with six cycles of cisplatin and doxorubicin, as described previously. Fourteen of the patients had invasion to the outer third of the myometrium, seven had documented lymph node metastases, and five had positive peritoneal washings. With a median follow-up of 34 months, there were only four recurrences, giving a projected 5-year survival rate of 75%. This combination certainly justifies further study in a phase III trial of adjuvant chemotherapy