Prognosis of isolated tumor cells and use of molecular classification in early stage endometrioid endometrial cancer.

We assessed the prognosis and molecular subtypes of early stage endometrioid endometrial cancer with isolated tumor cells within sentinel lymph nodes (SLNs) compared with node negative disease. Patients diagnosed with stage IA, IB, or II endometrioid endometrial cancer and primary surgical management were identified from January 1, 2007 to December 31, 2019. All SLNs underwent ultrastaging according to the institutional protocol. Patients with cytokeratin positive cells, micrometastases, and macrometastases were excluded. Clinical, pathology, and molecular subtype data were reviewed. Overall, 1214 patients with early stage endometrioid endometrial cancer met the inclusion criteria, of whom 1089 (90%) had node negative disease and 125 (10%) had isolated tumor cells. Compared with node negative disease, the presence of isolated tumor cells had a greater association with deep myometrial invasion, lymphovascular space invasion, receipt of adjuvant therapy, and adjuvant chemotherapy with or without radiation (p<0.01). There was no significant difference in survival rates between patients with isolated tumor cells and node negative disease (3 year progression free survival rate 94% vs 91%, respectively, p=0.21; 3 year overall survival rate 98% vs 96%, respectively, p=0.45). Progression free survival did not significantly differ among patients with isolated tumor cells who received no adjuvant therapy or chemotherapy with or without radiation (p=0.31). There was no difference in the distribution of molecular subtypes between patients with isolated tumor cells (n=28) and node negative disease (n=194; p=0.26). Three year overall survival rates differed significantly when stratifying the entire cohort by molecular subtype (p=0.04). Patients with isolated tumor cells demonstrated less favorable uterine pathologic features and received more adjuvant treatment with similar survival compared with patients with nodenegative disease. Among the available data, molecular classification did not have a significant association with the presence of isolated tumor cells, although copy number-high status was a poor prognostic indicator in early stage endometrioid endometrial cancer.

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Competing interests: BW reports research support by Repare Therapeutics, outside of the current work. CAA reports clinical trial funding paid to the institution from AstraZeneca; funding paid to the institution from BMS and SELLAS Life Sciences Group; consulting fees (advisory board) from Eisai/Merck, Roche/Genentech, Abbvie, AstraZeneca/Merck, and Repare Therapeutics; advisory board participation (no fee) for Blueprint Medicine; and leadership/fiduciary roles for the GOG Foundation Board of Directors (travel cost reimbursement) and NRG Oncology Board of Directors (unpaid). DZ reports institutional grants from Genentech, AstraZeneca, BMS, SELLAS Life Sciences Group, and Plexxikon; personal fees from Genentech, AstraZeneca, Xencor, Memgen, Synthekine, Celldex, and Hookipa; and stock options from Immunos, Accurius, Mana Therapeutics, and Calidi Biotherapeutics, outside of the submitted work. DZ is also an inventor on a patent related to the use of oncolytic Newcastle disease virus for cancer therapy. YLL reports research funding from AstraZeneca, GSK, and Repare Therapeutics. NRA-R reports research funding paid to the institution from GRAIL. ML reports research funding paid to the institution from KCI/Acelity, ad-hoc speaker for Intuitive Surgical, and advisory board participation for JnJ/Ethicon and Takeda. VM reports advisory board participation (unpaid) for Eisai, Merck, Clovis, Faeth, Duality, Morphyes, Karyopharm, Novartis, Lilly, and Immunocore. CFF reports participation in the scientific advisory boards for Merck (LYNK-002) and Genentech (MyPathway) without compensation, consulting for Seagen and Bristol Myers Squibb, and institutional research funds from Genentech/Roche, Bristol Myers Squibb, Merck, AstraZeneca, and Daiichi. SC serves as a consultant for AstraZeneca.