Elsevier

Gynecologic Oncology

Volume 111, Issue 2, November 2008, Pages 249-254
Gynecologic Oncology

A retrospective assessment of outcomes of chemotherapy-based versus radiation-only adjuvant treatment for completely resected stage I–IV uterine carcinosarcoma

https://doi.org/10.1016/j.ygyno.2008.06.035Get rights and content

Abstract

Purpose

To determine the progression-free survival (PFS) and overall survival (OS) in a cohort of patients who received either platinum-based chemotherapy with or without radiation therapy (pelvic or WAI), or RT alone.

Methods

Memorial Sloan-Kettering Cancer Center (MSKCC) electronic medical records from 8/1/1995 to 10/3/2007 were reviewed for patient age, diagnosis date, type of primary surgery, residual disease at the completion of primary surgery, FIGO stage, treatment details, dates of progression and death, and site(s) of first recurrence. PFS and OS by stage (I/II v III/IV) and by treatment type (chemotherapy with or without RT v RT alone) were determined using landmark analyses 8 weeks after surgery. Patients who received chemotherapy with or without RT (pelvic or abdominal) or RT alone (pelvic or abdominal) were included in the analysis. Both groups were allowed to have received intravaginal radiation therapy (IVRT).

Results

Forty-nine patients met study criteria. Thirty-eight/49 patients received chemotherapy: 23/38 (60.5%) received paclitaxel-carboplatin; 7/38 (18.4%) received ifosfamide-platinum; 8/38 (21.0%) received other chemotherapy. FIGO stage was: I = 15 (31%); II = 5 (10%); III = 21 (43%); IV = 8 (16%). Three-year PFS for the entire cohort was 24%. Three-year OS for the entire cohort was 60%. Three-year median PFS time for the entire cohort was 15 months (95% CI: 11–25 months). Three-year median OS time for the entire cohort was 67 months (95% CI: 23–89 months). Three-year PFS for stages I–II was 43% v 14% for stages III–IV (HR = 1.98 [0.9–4.33]); P = 0.082. Three-year OS for stages I–II was 68% v 55% for stages III–IV (HR = 1.26 [0.47–3.41]); P = 0.648. Three-year PFS for chemotherapy with or without RT was 35% v 9% for RT alone (HR = 1.74 [0.79–3.85]); P = 0.164. Three-year OS for chemotherapy with or without RT was 66% v 34% for RT alone (HR = 2.02 [0.77–5.33]); P = 0.146.

Conclusions

Our study corroborates GOG 150 results, and shows that paclitaxel-carboplatin appears to be an efficacious adjuvant chemotherapy regimen for completely resected uterine carcinosarcoma. The role of adjuvant RT in addition to chemotherapy warrants further investigation.

Introduction

Carcinosarcoma (CS) of the uterus is a rare, aggressive malignancy with a great capacity for metastasis. Uterine sarcomas represent approximately 4% of all invasive uterine cancers with an annual incidence rate of < 2 per 100,000 females [1], [2]. Surgical stage at diagnosis is the most important prognostic factor, but the prognostic significance of cell type, grade, mitotic count of sarcomatous component, and depth of myometrial invasion is unknown [4], [5], [6]. Uterine carcinosarcomas have a high propensity for pelvic and paraaortic lymph node involvement, and the optimal initial management includes surgical staging consisting of total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO), lymph node dissection (LND), resection of any gross intra-abdominal disease, and sampling of peritoneal washings [7].

Optimal initial management in CS has been investigated, and as yet, no consensus exists. GOG 150 was a randomized phase III trial of whole abdominal irradiation (WAI) v cisplatin-ifosfamide-mesna (CIM) as post-surgical treatment for stages I–IV CS. In this study, patients with stages I–IV primary CS of the uterus or cervix who underwent a TAH, BSO, and optimal tumor debulking to < 1 cm of residual disease were eligible. Peritoneal cytology and lymph node dissection were optional. Patients who received prior chemotherapy and/or radiation therapy, or who had a concomitant malignancy (other than non-melanoma skin cancer) within 5 years of uterine CS diagnosis were ineligible. Patients were randomized to WAI v CIM chemotherapy, and treatment had to begin within 8 weeks following surgery. This study required 11 years to meet accrual goals. After adjusting for stage and age, the recurrence rate at 5 years was 21% lower for CIM v WAI (relative hazard [RH] = 0.789, 95% confidence interval [CI]: (0.530–1.176), P = 0.245, 2-tail test). The death rate was 29% lower for CIM v WAI (RH = 0.712, 95% CI: 0.484–1.048, P = 0.085, 2-tail test) [3].

Paclitaxel-carboplatin has demonstrated high objective response rates in small series of patients with advanced uterine carcinosarcoma [15]. Paclitaxel-carboplatin is commonly used in both the advanced-disease and the adjuvant setting, despite lack of phase III clinical trial data supporting such use. We aimed to determine whether PFS and OS in a cohort of CS patients who would have met GOG 150 eligibility criteria and received either platinum-based chemotherapy with or without RT (pelvic or WAI) or RT alone (pelvic or WAI) was similar to GOG 150 outcomes, in an era when most patients received paclitaxel-carboplatin rather than CIM. Both the chemotherapy with or without RT group and the RT alone group were allowed to have received intravaginal radiation therapy (IVRT).

Section snippets

Patient eligibility

MSKCC electronic medical records from 8/1/1995 to 10/3/2007 were reviewed for patient age, diagnosis date, type of primary surgery, residual disease at completion of primary surgery, stage, treatment (chemotherapy and radiation therapy), dates of progression and death, site(s) of first recurrence and toxic side effects. Only patients meeting GOG 150 eligibility criteria were included in data analysis. Previously untreated patients with stages I–IV CS of the uterus or cervix (without any

Patient characteristics

Patient characteristics are detailed in Table 1. Forty-nine patients were included in study analysis (58 patients were identified; 9 excluded for no treatment or IVRT only; 3 for progression within 8 weeks of surgery). Omentectomies were performed in 35/49 (74.1%) patients. Twenty/49 patients were stages I–II and 29/49 patients were stages III–IV. The median age was 66 years (range 49–76). Histologic subtypes were: 29/49 patients homologous; 20/49 heterologous. Patient race distribution was as

Discussion

Until recently no randomized phase III data regarding optimal management of uterine carcinosarcoma was available. GOG 150 was a phase III clinical trial of adjuvant WAI v three cycles of CIM chemotherapy as post-surgical therapy in stages I–IV optimally debulked uterine carcinosarcoma patients. When this study was designed 15 years ago, 3 cycles of CIM therapy were considered an appropriate experimental arm to compare to WAI. GOG 150 failed to show a statistically significant improvement in

Conflict of interest statement

The authors declare that there are no conflicts of interest.

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