Carcinosarcomas of the uterus (womb) are uncommon cancers accounting for 4.3% of all cancers of the womb. These rare cancers have poor prognosis; one of the reasons for the poor survival outcome is the fact that over a third of these cancers (carcinosarcomas) have already spread beyond the womb at the time of diagnosis.
The main treatment is surgery to remove the cancer, however, because of the high rates of both local and distant recurrence after surgery, effective adjuvant therapies are needed. This review has shown that women with high stage disease (stage III-IV persistent or recurrent disease) who received combination chemotherapy including ifosfamide had a lower risk of death and disease progression than women who received ifosfamide alone, after adjustment for performance status.
In addition, radiotherapy to the abdomen was not associated with improved survival, as we found in one trial that there was no difference in the risk of death and disease progression in women who received whole abdominal irradiation and chemotherapy, after adjustment for age and stage of disease. Previous studies have shown that doxorubicin, despite being established in the treatment of uterine carcinoma, does not seem to be highly active.
Adverse events were comprehensively reported for the comparisons of combination therapy and ifosfamide and whole body irradiation and chemotherapy. More women experienced side effects when they received combination therapy than ifosamide alone and chemotherapy than whole body irradiation. The effect of therapy on quality of life was not reported in any of the trials.
In advanced stage metastatic uterine carcinosarcoma as well as recurrent disease adjuvant combination, chemotherapy with ifosfamide should be considered. Combination chemotherapy with ifosfamide and paclitaxel is associated with lower risk of death compared with ifosfamide alone. In addition, radiotherapy to the abdomen is not associated with improved survival.
Uterine carcinosarcomas are uncommon with about 35% not confined to the uterus at diagnosis. The survival of women with advanced uterine carcinosarcoma is poor with a pattern of failure indicating greater likelihood of upper abdominal and distant metastatic recurrence.
To evaluate the effectiveness and safety of adjuvant radiotherapy and/or systemic chemotherapy in the management of uterine carcinosarcoma.
We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), 2012, Issue 10, MEDLINE and EMBASE up to November 2012. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field.
Randomised controlled trials (RCTs) comparing adjuvant radiotherapy and/or chemotherapy in women with uterine carcinosarcoma.
Two review authors independently abstracted data and assessed risk of bias. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and risk ratios (RRs) comparing adverse events in women who received radiotherapy and/or chemotherapy were pooled in random-effects meta-analyses.
Three trials met the inclusion criteria and these randomised 579 women, of whom all were assessed at the end of the trials. Two trials assessing 373 participants with stage III to IV persistent or recurrent disease, found that women who received combination therapy had a significantly lower risk of death and disease progression than women who received single agent ifosfamide, after adjustment for performance status (HR = 0.75, 95% confidence interval (CI): 0.60 to 0.94 and HR = 0.72, 95% CI: 0.58 to 0.90 for OS and PFS respectively). There was no statistically significant difference in all reported adverse events, with the exception of nausea and vomiting, where significantly more women experienced these ailments in the combination therapy group than the Ifosamide group (RR = 3.53, 95% CI: 1.33 to 9.37).
In one trial there was no statistically significant difference in the risk of death and disease progression in women who received whole body irradiation and chemotherapy, after adjustment for age and FIGO stage (HR = 0.71, 95% CI: 0.48 to 1.05 and HR = 0.79, 95% CI: 0.53 to 1.18 for OS and PFS respectively). There was no statistically significant difference in all reported adverse events, with the exception of haematological and neuropathy morbidities, where significantly less women experienced these morbidities in the whole body irradiation group than the chemotherapy group (RR= 0.02, 95% CI: 0.00 to 0.16) for haematological morbidity and all nine women in the trial experiencing neuropathy morbidity were in the chemotherapy group).