D. Kadogami, Tanja Pejovic, Toru Sugiyama, Masato Nishimura, Takashi Sasaki, Shinya Matsuzaki, Erin A. Blake, Melissa Moffitt, Tadaaki Nishikawa, Lynda D. Roman, A. Wakatsuki, Takuya Moriya, Tsukasa Baba, Frederick R. Ueland, M. Yoshida, Kiyoshi Yoshino, Munetaka Takekuma, Mian M.K. Shahzad, Kazuaki Suda, H. Yoshida, Merieme Klobocista, Miriam D. Post, Kei Kawana, Tetsuro Oishi, T. Yokoyama, Hiroko Machida, Hiroshi Kajiwara, Esther Elishaev, Ken Yamaguchi, Yasuhiko Shiki, M. Andoh, Mikio Mikami, Yutaka Takazawa, Joseph L. Kelley, Tadashi Kimura, Abby M. Richmond, Tomoyuki Fukagawa, Tadayoshi Nagano, Masanori Yasuda, Y. Hazama, I. Podzielinski, Y. Ikeda, D. D. Im, K. Fujiwara, Norichika Ushioda, Koichiro Shimoya, Muneaki Shimada, Marian S. Johnson, Masako Shida, Sosuke Adachi, Koji Matsuo, Y. Ueda, Stephen H. Bush, Shinya Satoh, Ikuo Konishi, Kohei Omatsu, Takayuki Enomoto, Takahito Miyake, K. Iwasaki, Rouzan G. Karabakhtsian, Yoshiaki Yuba, Malcolm S. Ross, Tadao Takano, Terry K. Morgan, Todd B. Sheridan, Satoshi Takeuchi, Kosei Hasegawa, S. W. Li, Paulette Mhawech-Fauceglia, Mayu Yunokawa, and Ardeshir Hakam
To examine the effect of the histology of carcinoma and sarcoma components on survival outcome of uterine carcinosarcoma.A multicenter retrospective study was conducted to examine uterine carcinosarcoma cases that 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 to clinico-pathological demographics and outcomes.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 myometrial invasion, lymphovascular space invasion, and advanced-stage disease were independently associated with decreased PFS (all, P0.01). Both postoperative chemotherapy (5-year rates, 48.6% versus 39.0%, P0.001) and radiotherapy (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 improved PFS [hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.27-0.43, P0.001]. On univariate analysis, significant treatment benefits for PFS were seen with ifosfamide for low-grade carcinoma (82.0% versus 49.8%, P = 0.001), platinum for high-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, and anthracycline for low-grade carcinoma, and anthracycline for homologous sarcoma had no effect on PFS compared with non-chemotherapy group (all, P0.05). On multivariate analysis, ifosfamide for low-grade/homologous (HR 0.21, 95% CI 0.07-0.63, P = 0.005), platinum for high-grade/homologous (HR 0.36, 95% CI 0.22-0.60, P0.001), and anthracycline for high-grade/heterologous (HR 0.30, 95% CI 0.14-0.62, P = 0.001) remained independent predictors for improved PFS. Analyses of 1096 metastatic sites showed that carcinoma components tended to spread lymphatically, while sarcoma components tended to spread loco-regionally (P0.001).Characterization of histologic pattern provides valuable information in the management of uterine carcinosarcoma.