Gulisa Turashvili1, Natalia R Gómez-Hidalgo2, Jessica Flynn3, Mithat Gonen3, Mario M Leitao4, Robert A Soslow1, Rajmohan Murali5. 1. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 2. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 3. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 4. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA. 5. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: MuraliR@mskcc.org.
Abstract
OBJECTIVE: Determining whether carcinomas concurrently involving endometrium and ovary are independent primary tumors (IPTs) or endometrial carcinomas with ovarian metastases (at least stage IIIA endometrial cancers, IIIA-EC) using clinicopathologic criteria is often challenging. Recent genomic studies showed that most such tumors are clonally related. We sought to identify clinicopathologic features associated with clinical outcomes, and to separate women with these tumors into clinically low-risk and high-risk groups. METHODS: We reviewed clinical and pathologic data from 74 women who, between 1993 and 2014, underwent primary surgery for endometrial cancer and had concurrent ovarian involvement. RESULTS: The endometrial carcinomas were endometrioid (EECs, n = 41) or non-endometrioid (ENECs, n = 33). Nineteen (26%) cases were originally classified as IPTs using clinicopathologic criteria. Multivariate analysis revealed that lymph node involvement (hazard ratio (HR) = 2.38, 95% CI 1.13-5.02, p = 0.023) and non-endometrioid endometrial tumor histology (HR = 6.27, 95% CI 2.6-15.13, p < 0.001) were associated with poorer progression-free survival (PFS). Multivariate analysis of 65 women with known lymph node status revealed two prognostically distinct groups: a high-risk group comprising ENECs with ≥50% myometrial invasion irrespective of lymph node status (n = 21; median PFS 12.7 months, 95% CI, 9.24-19.8); and a low-risk group consisting of all EECs, as well as lymph node-negative ENECs with <50% myometrial invasion (n = 44, median PFS not reached). The risk-based classification was superior to the original classification of endometrial cancers as IPTs vs. IIIA-EC for predicting PFS (log-rank test, p < 0.001 vs. p = 0.07). CONCLUSION: Our proposed risk-based stratification enables categorization of women with concurrent endometrial and ovarian tumors according to their likely clinical outcomes.
OBJECTIVE: Determining whether carcinomas concurrently involving endometrium and ovary are independent primary tumors (IPTs) or endometrial carcinomas with ovarian metastases (at least stage IIIA endometrial cancers, IIIA-EC) using clinicopathologic criteria is often challenging. Recent genomic studies showed that most such tumors are clonally related. We sought to identify clinicopathologic features associated with clinical outcomes, and to separate women with these tumors into clinically low-risk and high-risk groups. METHODS: We reviewed clinical and pathologic data from 74 women who, between 1993 and 2014, underwent primary surgery for endometrial cancer and had concurrent ovarian involvement. RESULTS: The endometrial carcinomas were endometrioid (EECs, n = 41) or non-endometrioid (ENECs, n = 33). Nineteen (26%) cases were originally classified as IPTs using clinicopathologic criteria. Multivariate analysis revealed that lymph node involvement (hazard ratio (HR) = 2.38, 95% CI 1.13-5.02, p = 0.023) and non-endometrioid endometrial tumor histology (HR = 6.27, 95% CI 2.6-15.13, p < 0.001) were associated with poorer progression-free survival (PFS). Multivariate analysis of 65 women with known lymph node status revealed two prognostically distinct groups: a high-risk group comprising ENECs with ≥50% myometrial invasion irrespective of lymph node status (n = 21; median PFS 12.7 months, 95% CI, 9.24-19.8); and a low-risk group consisting of all EECs, as well as lymph node-negative ENECs with <50% myometrial invasion (n = 44, median PFS not reached). The risk-based classification was superior to the original classification of endometrial cancers as IPTs vs. IIIA-EC for predicting PFS (log-rank test, p < 0.001 vs. p = 0.07). CONCLUSION: Our proposed risk-based stratification enables categorization of women with concurrent endometrial and ovarian tumors according to their likely clinical outcomes.
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