Treatment of patients with sarcoma of the uterus

In the present series of 156 patients with sarcomas of the uterus the therapeutic modalities employed were evaluated. The 5-year survival rate of 51.3% was obtained for this series including 41.2% for leiomyosarcomas, 57.1% for endometrial stromal sarcomas, 50.0% for mixed mesodermal tumors and 40.0% for carcinosarcomas. The prognostic significance of the extent of disease, histological type and the age of patients is emphasised. Clinical features of uterine sarcomas specific for different histological types were shown: leiomyosarcomas were characterized by a rapid tumor growth while uterine bleeding in the background of neuroendocrine disturbances similar to those observed in endometrial carcinomas were related to endometrial stromal sarcomas and mixed mesodermal tumors. In respect to early diagnosis of sarcomas an ultrasonic pelvic examination and studies of aspirate specimens taken from the uterine cavity are recommended to be performed for the groups at high risk. An individual treatment policy was developed for each sarcoma patient depending on the histological type, the stage of disease and general condition of the patient. Surgical approach varied ranging from a total hysterectomy and adnexectomy, done for leiomyosarcomas, to an extended hysterectomy and pelvic lymphadenectomy for mixed mesodermal tumors and endometrial stromal sarcomas. Postoperative distant and/or endovaginal radiation are indicated for all histological types of sarcomas excepting leiomyosarcomas. Application of adjuvant chemotherapy with carminomycin or adriamycin improves the results of treatment.     

复发性子宫肉瘤的诊治

子宫肉瘤是罕见的女性生殖道恶性肿瘤,从组织学类型可分为子宫平滑肌肉瘤、子宫内膜间质肉瘤和恶性混合性中胚叶瘤。复发率高,治疗以手术、化疗等综合治疗为主,放疗效果不确切,可以协助控制局部复发,抗雌激素治疗也有一定效果。影响预后的因素很多,主要是临床期别和肿瘤大小。     

Solid malignant uterine tumours

Uterine sarcomas are a rare group of uterine tumours. The majority consist of leiomyosarcomas, endometrial stromal and mixed mesodermal sarcomas. The most important treatment for this tumour group is removal of the uterus. Radiotherapy is of use in reducing the incidence of local relapse but its effect on the 5-year survival is not proven. Trials are currently evaluating chemotherapy for advanced or recurrent disease the most active agents being ifosfamide and doxirubicin.     

The role of lymphadenectomy in uterine leiomyosarcoma: review of the literature and recommendations for the standard surgical procedure

Uterine sarcomas are rare and aggressive gynaecologic malignancies with poor prognosis, arising from myometrial or endometrial tissue. These rare cancers can be aggressive, and account for a greatly disproportionate amount of deaths from uterine cancers. The histological uterine sarcomas classification includes carcinosarcomas (malignant mesodermal mixed tumors), accounting for 40% of cases, leiomyosarcomas (40%) and endometrial stromal sarcomas (10–15%). Each group of these tumors presents differences in diagnosis, prognostic factors, treatment, and outcome. Uterine leiomyosarcomas typically affects women in their sixth decade of life, presenting with atypical symptoms such as abnormal uterine bleeding and abdominal pain. The optimal treatment of uterine leiomyosarcomas is surgery, including total abdominal hysterectomy and bilateral salpingooophorectomy. The aim of this study was to conduct a systematic review of the literature regarding the standard surgical procedure of uterine leiomyosarcomas and investigate whether lymphadenectomy affects the 5-year DSS, as well as other relevant clinical outcomes, in women with uterine leiomyosarcomas. For this purpose, MEDLINE, EMBASE, and the Cochrane Library databases were reviewed, and a critical account of the management strategies of these tumors is presented.     

Primary sarcoma of the adult vagina: a clinicopathologic study

Combination chemotherapy has dramatically improved the results of treatment for embryonal rhabdomyosarcoma of the vagina in children, but little attention has been directed toward vaginal sarcomas in adults. This report of 17 cases of primary sarcoma of the adult vagina includes ten leiomyosarcomas, four mixed mesodermal tumors, one undifferentiated sarcoma, one stromal sarcoma, and one neurofibrosarcoma. The leiomyosarcomas, mixed mesodermal tumors, and the stromal sarcoma were morphologically similar to their uterine counterparts. Thirty-five percent of the patients had received pelvic irradiation for carcinoma of the cervix. Three of four patients treated by pelvic exenteration are alive and disease free after 84 to 161 months of observation. All 13 patients who received other forms of primary therapy died of recurrence. The pelvis was the first site of recurrence in all treatment failures and the only site of failure in 50%.     

Uterine sarcomas: the Curie Institut experience. Prognosis factors and adjuvant treatments

PURPOSE: With a retrospective study at a single institution, we propose to analyze the prognosis factors and adjuvant treatment for uterine sarcomas. MATERIALS AND METHODS: From 1975 to 1995, 73 uterine sarcomas were treated at the Institut Curie, corresponding to 61 T1, 5 T2, and 8 T4 tumors. Thirteen patients had metastatic disease at the time of diagnosis. The mean age was 58 years. In 71% of patients, the presenting sign was bleeding. This series consisted of 44% leiomyosarcomas (LMS), 19% endometrial stromal sarcomas (ESS), and 31% carcinosarcomas or mixed mesodermal sarcomas (MMS). For the grading classification, we used the classification of the Sarcoma Group of the French Federation of Cancer Centres for soft tissue sarcomas. Of the patients, 66% presented a high-grade tumor. RESULTS: The median overall survival was 42 months, with a 5-year survival of 45%. Histological grade, FIGO stage, histology types, and menopausal status were the four independent factors in multivariate analysis. Eighteen patients relapsed locally (25.7%), with 77% central pelvic sites. Patients with radiotherapy and ESS had better local control in multivariate analysis. Thirty-four patients developed metastases (48.6%), mainly pulmonary (58.8%). Eight patients presented with peritoneal disease. High grades and LMS had the worst survival without metastasis in multivariate analysis. CONCLUSION: This study validated our classification for sarcoma grading and confirmed the finding of worst prognosis for LMS and the importance of radiotherapy in local control.     

Prognostic factors and expression of p53 and mdm-2 in uterine sarcomas

Objectives: To evaluate the clinicopathologic prognostic factors of uterine sarcoma, and determine whether overexpression of p53 and mdm-2 proteins correlate with overall survival and prognostic factors. Methods: Thirty specimens from 43 patients with uterine sarcoma were available for slide review and evaluated by immunohistochemistry at Yonsei and Ajou University Medical Centers for the expression of p53 and mdm-2. Results: Overall survival was found to correlate to histologic type of uterine sarcoma, surgical stage, tumor grade, and mitotic index. Whereas 63% of the sarcomas expressed p53, with a significant correlation to overall survival, 60% expressed mdm-2, with a significant correlation to the mitotic index but not to overall survival. Conclusion: Histologic type, surgical stage, tumor grade, mitotic index, and p53 expression were prognostic factors of the overall survival of patients with uterine sarcoma.     

Uterine sarcomas: A clinicopathologic study, 1965–1981

Forty-six cases diagnosed as uterine sarcoma from 1965 to 1981 were analyzed. Using mitotic count, 7 of 21 leiomyosarcomas (LMS) were redesignated leiomyomas and all are NED. The actuarial survival rates for the 38 considered sarcomas were 55 and 27% at 2 and 5 years. (The 22 patients eligible for 5-year follow-up had a 27% absolute survival, with 3 of 22 NED.) Fourteen LMS patients had a superior 5-year actuarial survival (42%) than 18 malignant mixed mesodermal (MMM) patients (15%), but the difference disappears when only patients under 70 are considered. Stage and age were the most important prognostic indicators. Complete surgical resection was essential for long-term survival. Six resected patients given adjuvant chemotherapy (mostly VAC) had an improved actuarial survival (61 vs 15% for the 23 resected patients not receiving chemotherapy). Seventy percent of 23 recurrences occurred within 2 years and average survival post-recurrence was 7.6 months. Survival post-recurrence for 8 patients was not improved by chemotherapy. Seventy-eight percent of recurrences had a distal component, with lung being the most common site.     

Uterine Inversion as a Result of a Large Prolapsed Carcinosarcoma of the Uterus

BackgroundUterine inversion is most commonly seen in labour and delivery. However, it can be associated with uterine tumours, including gynaecologic malignancy.CaseIn a 66-year-old woman, uterine inversion identified at laparotomy that was found to be associated with uterine carcinosarcoma (malignant mixed mesodermal tumour) represents an unusual presentation. Surgical approach necessitated a vertical hysterotomy to amputate and deliver the uterine tumour.ConclusionUterine inversion in gynaecologic oncology may be associated with sarcoma or malignant mixed mesodermal tumour. This can represent a diagnostic and surgical challenge and should be considered.     

Systemic therapy for advanced uterine sarcoma: a systematic review of the literature

OBJECTIVE: To conduct a systematic review of the literature regarding the systemic treatment of advanced uterine sarcoma and provide an evidence-based summary of the available literature. METHODS: MEDLINE, EMBASE, and the Cochrane Library databases were searched. "Uterine sarcoma," "leiomyosarcoma," "mixed mesodermal tumor," "chemotherapy," and "systemic therapy" were combined with the search terms for study designs. RESULTS: Three randomized controlled trials and 24 prospective phase II trials were included in the systematic review. In a randomized trial of doxorubicin versus doxorubicin plus cyclophosphamide for advanced or recurrent uterine sarcoma, doxorubicin produced an overall response rate (RR) of 19% and median survival of 11.6 months, which was similar to the response with combination chemotherapy (RR 19%, median survival 10.9 months). A randomized trial comparing ifosfamide plus cisplatin versus ifosfamide alone in mixed mesodermal tumors showed a significant improvement in RR and progression-free survival with the combination compared with ifosfamide alone, however, the combination was associated with increased toxicity including death. A randomized trial comparing doxorubicin to doxorubicin with dacarbazine in women with advanced or recurrent uterine sarcoma demonstrated a significantly higher RR with the combination (P < 0.05), but no significant difference in survival. CONCLUSIONS: Offering palliative chemotherapy to patients with advanced, unresectable uterine sarcoma who are symptomatic from this disease is a reasonable decision. Doxorubicin is an option for women with advanced uterine sarcoma. The combination of cisplatinum and ifosfamide is also an option for women with metastatic mixed mesodermal tumors; however, this combination is associated with significant toxicity when compared to ifosfamide alone.     

Treatment of uterine sarcoma. A survey of 49 patients

Purpose: Surgery, radiotherapy and chemotherapy are employed in the treatment of uterine sarcoma. We claim to evaluate the role of radiotherapy in the treatment of uterine sarcoma. Patients and methods: We report a retrospective study of 49 patients with uterine sarcoma treated from 1990–1999 at Masaryk Memorial Cancer Institute in Brno. All 49 patients had surgery, 19 (38.7%) had adjuvant radiotherapy and 25 (51%) had chemotherapy. Using the FIGO classification: 71.4% had stage I, 6.1% stage II, 16.3%, stage III and 6.1% stage IVa disease. 42.9% of tumors were mixed Müllerian tumors, 34.7% leiomyosarcomas and 22.4% endometrial stromal sarcomas. 12 cases (24.5%) had a local recurrence, 7 (14.3%) had hematogenous dissemination. There was an increased disease free interval (DFI) for patients treated with adjuvant radiotherapy (p=0.005). The DFI was favourably influenced by the stage of the disease. Of 12 patients with a local recurrence only one had postoperative radiotherapy. Radiotherapy had an impact on overall survival (OS). The five-year OS probability was 51.6% without radiotherapy and 88.9% with radiotherapy (p=0.0066). Conclusion: We conclude that postoperative radiotherapy in our series of patients diagnosed with uterine sarcoma has an impact on locoregional and disease-free progression intervals (LRFI, DFI) and overall survival (OS). The most important prognostic factor is the extend of the disease (stage). Stage I patients have a significantly better survival. Received: 2 April 2001 / Accepted: 18 June 2001     

Role of radiotherapy treatment of uterine sarcoma

Uterine sarcomas are rare and, consequently, data supporting the use of adjuvant radiotherapy in uterine sarcomas consist of few randomised studies and multiple single-institution retrospective reports. It is becoming increasingly clear that each histologic subtype of uterine sarcoma is a distinct entity for which tailored treatment recommendations are needed. In this review, we analysed the effect of adjuvant radiotherapy for the main histologic subtypes of uterine sarcomas. When grouping all histologies, adjuvant radiotherapy has been shown in most studies to reduce local-regional failure without an overall survival advantage, as distant failure is the predominant pattern of relapse. Carcinosarcomas have the strongest indication for adjuvant radiotherapy, especially in early stage disease. Women with leiomyosarcomas and endometrial stromal sarcomas receiving adjuvant radiotherapy have improved local control compared with women undergoing surgery alone. As distant failure rates decrease with improvements in systemic therapies, there may be a broader indication for adjuvant radiotherapy.     

Prognostic features of sarcomas and mixed tumors of the endometrium

A retrospective study of 103 patients with endometrial sarcomas treated at the University of Michigan Hospital includes 47 mixed homologous tumors, 32 mixed heterologous tumors, 21 pure homologous sarcomas (endometrial stromal sarcoma), and three pure heterologous sarcomas (rhabdomyosarcomas). Clinical characteristics appeared similar among the four patient groups. Fourteen percent of the patients had received previous pelvic irradiation. Twenty-nine percent of the patients with a clinical stage I or II tumor had extrauterine disease discovered at surgery. Extent of the tumor at the time of surgery strongly correlated with outcome, and only two patients with extrauterine disease were long-term survivors. Life table survival probability at five years was 58% with surgical stage I, 33% with surgical stage II, 13% with surgical stage III, 0 with surgical stage IV, and 5% in patients referred with recurrence. Risk factors predicting treatment failure were analyzed separately in surgical stages I and II using Cox model analysis. There was no difference in risk for treatment failure between pure endometrial stromal sarcoma, mixed homologous sarcoma, or mixed heterologous sarcoma. The strongest factor correlating with a poor outcome was deep myometrial invasion (P less than .001). An adverse trend was detected in those patients with previous pelvic irradiation, with advancing patient age, and with increasing uterine size, although these differences did not reach statistical significance. Neither the presence of heterologous tumor elements nor cervical involvement were found to be adverse prognostic factors.     

Limitations of adjuvant radiotherapy for uterine sarcomas spread beyond the uterus

OBJECTIVE: The present review analyzes patients with advanced uterine sarcomas with the goal of identifying patients likely to benefit from larger volumes and higher dosages of radiotherapy. METHODS: A retrospective review was performed of medical records of all patients receiving adjuvant radiotherapy for advanced uterine sarcomas from 1978 to 1997 at the University of Minnesota. RESULTS: Nineteen women with advanced uterine sarcomas received adjuvant radiotherapy. Seven also received adjuvant chemotherapy. Three patients had FIGO stage IIIA, 1 stage IIIB, 5 stage IIIC, and 12 stage IVB. Patients with mixed mullerian tumors had overall and disease-free survivals of 31% at 1 year and 23% at 5 years. For leiomyosarcomas, overall survival was 67% at 1 year and 33% at 5 years, but relapse-free survival was 33% at 1 and 5 years. First sites of failure were three pelvic and abdominal, one abdominal only, one abdominal and distant, two pelvic and distant, one pelvic, abdominal, and distant, five distant only, and one unknown. No Grade 3 or 4 toxicity occurred. CONCLUSION: Ongoing technical advancements in radiotherapy offer more precise radiation delivery, particularly to the peritoneal cavity. Although abdominal failures are common in women with mixed mullerian tumors, translation of higher radiation dosage to cure is unproven, and the majority of failures have a distant component. Until effective systemic therapy is developed, the prognosis of uterine sarcomas with any spread beyond the uterus will remain poor.     

Clinical outcome and prognostic factors in 100 cases of uterine sarcoma: experience in Helsinki University Central Hospital 1990-2001

ObjectiveUterine sarcomas are rare malignant gynecological tumors with poor prognosis. In this study clinical data on all uterine sarcoma patients treated at Helsinki University Central Hospital (HUCH) between 1990–2001 were retrospectively evaluated.MethodsMedical records were reviewed and data collected on all uterine sarcomas treated during a 12-year period at HUCH. Kaplan–Meier survival curves were generated and those variables found to be statistically significant in univariate analysis were examined by multivariate analysis using Cox's proportional hazards regression model.ResultsOne hundred patients met the study requirements: 40 cases were diagnosed as carcinosarcomas, 39 as leiomyosarcomas and 21 as endometrial stromal sarcomas. First-line treatment was surgery in 98% of the patients. Seventy-eight of the patients were treated by means of adjuvant therapy. A complete response was achieved in 80% and a partial response in 4% of the cases. The 2-, 5- and 10-year overall survival rates were 62%, 51% and 38% and disease-specific survival rates were 64%, 56% and 44% (all sarcomas). In multivariate analysis, stage, age, tumor size and parity were proven to have independent influences on overall survival, and stage, tumor size and parity also independently influenced disease-specific survival.ConclusionsIn this study, survival rates were better than in nearly all previous retrospective studies of uterine sarcomas. It seems that higher parity could have a negative influence on survival in cases of uterine sarcoma.     

Adjuvant chemotherapy following surgery in the management of uterine sarcomas

OBJECTIVE: The aim of this study was to investigate the use of imaging tools in the diagnosis of uterine sarcomas, and to evaluate the effect of the adjuvant chemotherapy for uterine sarcomas. PATIENTS AND METHODS: The data of 29 patients with uterine sarcomas who received cytostatic polychemotherapy between 1990 and 2000 at the Oncological Division of the Ist Department of Obstetrics and Gynecology, Semmelweis University were evaluated by the authors. Symptoms leading to diagnosis and methods of diagnosis were examined. Vascular changes shown by two-dimensional, color and pulsed Doppler ultrasonography were observed. For staging the currently accepted FIGO method was adopted. Most of the patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH & BSO). In each case we administered adjuvant combination chemotherapy according to the CYVADIC-protocol. The effect of adjuvant chemotherapy was evaluated. RESULTS: Six patients had Stage I, ten had Stage II, 11 had Stage III, and two had Stage IV disease. The mean age of the patients was 53.6 years with a range of 22 to 77 years. Histopathologic distribution included nine leiomyosarcomas (LMS), 13 mixed mesodermal sarcomas (MMS), and seven endometrial stromal sarcomas (ESS). Although most patients experienced neutropenia following cytotoxic chemotherapy, other non-hematologic adverse effects were easy to control. The average progression-free interval was 22.14 months, in which no significant difference was found between the histologic types. Different stages showed highly varied responses: surprisingly, patients in Stage IV with lung metastases were documented to have the longest progression-free survival. The three-year survival rate for all stages was demonstrated in 34.4% of cases. Patients with progressive disease had an average survival period of 4.4 months. CONCLUSIONS: These findings suggest that adjuvant cytostatic therapy for patients with distant metastasis confined to a single organ may produce better results than expected.     

Expression of intermediate filaments in ovarian and uterine tumors

We studied the expression of cytoskeletal intermediate filaments in different types of ovarian and uterine sarcomas and carcinomas. In both uterine and ovarian leiomyosarcomas, in endometrial stromal sarcomas, and also in ovarian sarcomas, most tumor cells appeared to be positive for desmin, the muscle type of intermediate filament protein. In most of the tumors, vimentin was present only in some neoplastic cells and in the vascular endothelia. Interestingly, both uterine and ovarian malignant mixed mesodermal tumors appeared to express several types of intermediate filaments, most of the stromal cells being positive for vimentin or desmin, and the epithelial component expressing keratin. The results show that most of the sarcomatous tumors of the ovary and uterus express mainly muscle type of intermediate filament protein. The results also demonstrate the ability of cells of mesodermal origin to express epithelial cytoskeleton markers--cytokeratins.     

Uterine sarcomas: prognostic factors and treatment modalities--study on 209 patients

From 1975 through 1984, 209 patients with uterine sarcoma were studied in 13 French Oncology Centers. The repartition by histologic type was the following: 31 patients (PTS) with carcinosarcoma, 81 PTS with leiomyosarcoma, 27 PTS with endometrial sarcoma, and 70 PTS with mullerian mixed mesodermal tumors. The prognostic factors were analyzed using a proportional hazards regression model. The analysis of prognostic factors showed that the strongest predictor of survival was menopausal status. Increasing tumor extension and increasing WHO performance status were also prognostic factors. No significant difference for prognosis was found for histologic type, operability, and age. Two-year survival rates were quite similar for all kinds of treatment, being 58.0% for tumor extension T1 and T2 and 35.0% for tumor extension T3 and T4. Two-year recurrence and metastasis rates were lower with addition of radiotherapy or chemotherapy without any benefit on survival rates. Cooperative clinical trials including all histologic types should be undertaken to improve survival. The knowledge of the prognostic factors can help to refine treatment comparisons.     

子宫混合性恶性中胚叶瘤(附25例临床分析)

目的：探讨子宫混合性恶性中胚叶瘤的诊断及治疗方法对患者预后的影响。方法：回顾性分析1966～1995年经治疗的25例子宫混合性恶性中胚叶瘤患者的临床资料。结果：本组患者中，11例生存期≥2a，其中2例Ⅰ期早患者存活分别≥5a和≥10a。结论：子宫混合性恶性中胚叶瘤较少见，恶性程度高，患者预后不良。在诊断上，应重视术前诊刮和病理学检查。治疗方法上除Ⅰ期早可行单纯手术治疗外，其它各期均应在术前、术后辅以放疗、化疗等综合治疗。     

Uterine sarcoma occurring in a premenopausal patient after uterine artery embolization: a case report and review of the literature

OBJECTIVE: We report a case of uterine leiomyosarcoma occurring after uterine artery embolization and review the previously published cases. We estimate the incidence of sarcoma after UAE, the mean diagnostic delay in young women undergoing this procedure and review the potential and limits of preoperative procedures in diagnosing uterine sarcomas. CASE REPORT: A 35-year-old woman had an early failure after UAE. She underwent surgery 13 months after the procedure. Final pathologic report was consistent with uterine leiomyosarcoma. CONCLUSION: Incidence of uterine sarcomas after UAE is low, probably similar to that of misdiagnosed leiomyosarcomas in women undergoing surgery for presumed symptomatic leiomyomas. Therefore a relation between the procedure and the malignancy seems to be very unlikely. Diagnostic delay in menstruated women younger than 50 undergoing UAE for presumed symptomatic leiomyoma ranges between 13 and 15 months. The safest procedure for women who fail the conservative management of leiomyoma with UAE is surgical, allowing for definitive pathologic exclusion of malignancy.