Adjuvant radiotherapy and/or chemotherapy after surgery for uterine carcinosarcoma

 

Abstract

Background

Uterine carcinosarcomas are uncommon with about 35% not confined to the uterus at diagnosis. The survival of patients with advanced uterine carcinosarcoma is poor with pattern of failure indicating greater likelihood of upper abdominal and distant metastatic recurrence.

Objectives

To evaluate the effectiveness and safety of radiotherapy and/or systemic chemotherapy in the management of stage III-IV persistent or recurrent uterine carcinosarcoma.

Search methods

We searched the Cochrane Gynaecological Cancer Group Trials Register, CENTRAL, The Cochrane Library 2010, Issue 2, MEDLINE and EMBASE to May 2010. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field.

Selection criteria

Randomised controlled trials comparing adjuvant radiotherapy and/or chemotherapy in women with uterine carcinosarcoma.

Data collection and analysis

We independently abstracted data and assessed risk of bias. We pooled hazard ratios (HRs) for overall and progression-free survival and risk ratios (RRs) comparing adverse events in women who received radiotherapy and/or chemotherapy in meta-analyses.

Main results

Three trials (579 women, of whom all were assessed at the end of the trials) met the inclusion criteria. Two trials (373 women with stage III-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. There was no statistically significant difference in all reported adverse events, with the exception of nausea and vomiting, which affected significantly more women in the combination therapy group than in the ifosamide group.

One trial found no statistically significant difference in the risk of death and disease progression in women who received whole abdominal 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 overall survival and progression-free survival respectively). There was no statistically significant difference in all reported adverse events, with the exception of haematological and neuropathy morbidities, which affected significantly fewer women in the whole body irradiation group than in the chemotherapy group (RR = 0.02, 95% CI 0.00 to 0.16).

Authors' conclusions

The results of this review are limited to two trials. In the primary treatment/ first line therapy of advanced stage metastatic uterine carcinosarcoma, as well as in recurrent disease, adjuvant combination chemotherapy with ifosfamide and paclitaxel should be considered. None of the included studies reported on quality of life.

 

Plain language summary

The addition of chemotherapy and/or radiation treatment after surgery in carcinosarcoma of the womb

Carcinosarcomas of the uterus (womb) are uncommon cancers accounting for 4% of all cancers of the womb.These uncommon 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 with ifosfamide and paclitaxel had 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 effective.

Adverse events were comprehensively reported and showed that more women experienced side effects when they received combination therapy than ifosamide alone and more women experienced side effects when they received chemotherapy than whole body irradiation. The degree to which these treatments affect patients' quality of life remains unknown as quality of life measures were not reported in any of the trials.

 

Resumen

Antecedentes

Quimioterapia y radioterapia adyuvante después de la cirugía para el carcinosarcoma uterino

Los carcinosarcomas uterinos son poco frecuentes y cerca del 35% no está limitado al útero en el momento del diagnóstico. La supervivencia de las pacientes con carcinosarcoma uterino avanzado es pobre y el patrón de fracaso indica mayor probabilidad recidiva metastásica abdominal superior y a distancia

Objetivos

Evaluar la efectividad y seguridad de la radioterapia y la quimioterapia sistémica en el tratamiento del carcinosarcoma uterino persistente o recidivante en estadio III y IV

Estrategia de búsqueda

Se realizaron búsquedas en el Registro Especializado de Ensayos Controlados del Grupo Cochrane de Cáncer Ginecológico (Cochrane Gynaecological Cancer Group) CENTRAL, Cochrane Library 2010, número 2, MEDLINE y EMBASE hasta mayo 2010. También se buscó en los registros de ensayos clínicos, los resúmenes de reuniones científicas, las listas de referencias de los estudios incluidos y se estableció contacto con expertos en el campo.

Criterios de selección

Ensayos controlados con asignación aleatoria que compararon radioterapia y quimioterapia adyuvante en mujeres con carcinosarcoma uterino.

Obtención y análisis de los datos

Se extrajeron los datos y se evaluó el riesgo de sesgo de forma independiente. Se agruparon los cocientes de riesgos instantáneos (CRI) para la supervivencia general y libre de progresión y los cocientes de riesgos (CR) que compararon los eventos adversos en las mujeres que recibieron radioterapia y quimioterapia en los metanálisis.

Resultados principales

Tres ensayos (579 mujeres evaluadas al finalizar los ensayos) cumplieron con los criterios de inclusión. En dos ensayos (373 mujeres con enfermedad persistente o recidivante en estadio III y IV) se halló que el riesgo de muerte y la evolución de la enfermedad fueron significativamente menores en las mujeres que recibieron el tratamiento de combinación que en las que recibieron ifosfamida como agente único. No se observaron diferencias estadísticamente significativas en todos los eventos adversos informados, excepto náuseas y vómitos, lo que afectó a más mujeres en el grupo de tratamiento de combinación que en el grupo de ifosfamida.

Un ensayo no encontró diferencias estadísticamente significativas en el riesgo de muerte y en la evolución de la enfermedad en las mujeres que recibieron irradiación abdominal y quimioterapia, después del ajuste según la edad y el estadio de la FIGO (CRI = 0,71; IC del 95%: 0,48 a 1,05 y CRI = 0,79; IC del 95%: 0,53 a 1,18 para la supervivencia general y la supervivencia libre de progresión respectivamente). No se observaron diferencias estadísticamente significativas en todos los eventos adversos informados, a excepción de la morbilidad hematológica y neuropática, lo que afectó a menos mujeres en el grupo de irradiación corporal total que en el grupo de quimioterapia (CR 0,02; IC del 95%: 0,00 a 0,16).

Conclusiones de los autores

Los resultados de esta revisión se limitan a dos ensayos. Debe considerarse la quimioterapia combinada adyuvante con ifosfamida y paclitaxel en el tratamiento primario/tratamiento de primera línea del carcinosarcoma uterino metastásico, así como en la enfermedad recidivante. Ninguno de los estudios incluidos informó sobre la calidad de vida.

Traducción

Traducción realizada por el Centro Cochrane Iberoamericano