Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma

Background: To examine the effect of the histology of carcinoma and sarcoma components on survival outcome ofuterine carcinosarcoma.Patients and methods: A multicenter retrospective study was conducted to examine uterine carcinosarcoma casesthat underwent primary surgical staging. Archived slides were examined and histologic patterns were grouped based on carcinoma (low-grade versus high-grade) and sarcoma (homologous versus heterologous) components, correlating toclinico-pathological demographics and outcomes.Results: Among 1192 cases identified, 906 cases were evaluated for histologic patterns (carcinoma/sarcoma)with high-grade/homologous (40.8%) being the most common type followed by high-grade/heterologous (30.9%),low-grade/homologous (18.0%), and low-grade/heterologous (10.3%). On multivariate analysis, high-grade/heterologous(5-year rate, 34.0%, P = 0.024) and high-grade/homologous (45.8%, P = 0.017) but not low-grade/heterologous (50.6%,P = 0.089) were independently associated with decreased progression-free survival (PFS) compared with low-grade/homologous (60.3%). In addition, older age, residual disease at surgery, large tumor, sarcoma dominance, deep myometrialinvasion, lymphovascular space invasion, and advanced-stage disease were independently associated withdecreased PFS (all, P < 0.01). Both postoperative chemotherapy (5-year rates, 48.6% versus 39.0%, P < 0.001) andradiotherapy (50.1% versus 44.1%, P = 0.007) were significantly associated with improved PFS in univariate analysis.However, on multivariate analysis, only postoperative chemotherapy remained an independent predictor for improvedPFS [hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.27-0.43, P < 0.001]. On univariate analysis, significant treatmentbenefits for PFS were seen with ifosfamide for low-grade carcinoma (82.0% versus 49.8%, P = 0.001), platinum forhigh-grade carcinoma (46.9% versus 32.4%, P = 0.034) and homologous sarcoma (53.1% versus 38.2%, P = 0.017),and anthracycline for heterologous sarcoma (66.2% versus 39.3%, P = 0.005). Conversely, platinum, taxane, andanthracycline for low-grade carcinoma, and anthracycline for homologous sarcoma had no effect on PFS compared withnon-chemotherapy group (all, P > 0.05). On multivariate analysis, ifosfamide for low-grade/homologous (HR 0.21, 95% CI0.07-0.63, P = 0.005), platinum for high-grade/homologous (HR 0.36, 95% CI 0.22-0.60, P < 0.001), and anthracyclinefor high-grade/heterologous (HR 0.30, 95% CI 0.14-0.62, P = 0.001) remained independent predictors for improvedPFS. Analyses of 1096 metastatic sites showed that carcinoma components tended to spread lymphatically, whilesarcoma components tended to spreadloco-regionally (P < 0.001).Conclusion: Characterization of histologic pattern provides valuable information in the management of uterinecarcinosarcoma.