Prognosis of isolated tumor cells and the utility of molecular classification in early stage endometrioid endometrial cancer (243)

Abstract

<b>Objectives:</b> To assess the prognosis of isolated tumor cells (ITCs) within sentinel lymph nodes (SLN) compared with node-negative (NN) disease in early-stage endometrioid endometrial cancer and to perform additional evaluation by molecular classification. <b>Methods:</b> Patients (pts) who underwent primary surgical management of uterine cancer from 2007-2019 with a final diagnosis of Stage IA, IB, and II endometrioid endometrial cancer were identified. All SLN underwent ultrastaging per institutional protocol. Cytokeratin-positive cells, ITCs with micrometastasis, and ITCs with macrometastasis were excluded. Clinical-pathologic variables were reviewed. Tumors were classified as POLE, MSI-H, CN-high, or CN-low, based on the TCGA, by utilizing MSK-IMPACT next-generation sequencing (NGS) results and tumor IHC staining. Appropriate statistical analyses were performed. <b>Results:</b> We identified 1381 pts who met the inclusion criteria: 1256 NN (91%) and 125 ITCs (9%). Adjuvant treatment was given to 85% of pts with ITCs compared to 40% of NN pts (p<0.01). Compared to NN patients, the presence of ITCs had a greater association with myoinvasion ≥50% (41% vs 13%, p<0.01), lymphovascular space invasion (77% vs 23%, p<0.01), and chemotherapy +/- radiation (62% vs 7%, p<0.01). The Median follow-up time was 36.5 months (0.4-167 months). There was no significant difference in survival when comparing node status (3-yr PFS: 94% ITC vs 90% NN, p=0.09; 3-yr OS: 98% ITC vs 96% NN, p=0.6). Progression-free survival of ITC-positive pts was not significantly different among those receiving no treatment, chemotherapy +/- radiation, or radiation (p=0.3; Figure 1). TCGA classification was available for 34 ITC and 300 NN pts. Distribution by molecular classification for ITC pts was 3% POLE, 35% MSI-H, 9% CN-high and 53% CN-low; for NN pts, 16% POLE, 36% MSI-H, 4% CN-high, and 43% CN-low (p=0.2). Molecular-based survival outcomes were performed for pts who underwent MSK-IMPACT prior to documented recurrence. There was a significant difference in survival when stratifying the entire cohort by molecular classification, with CN-high having worse outcomes (3-yr PFS: 73% vs 90-95%, p=0.046; 3-yr OS: 78% vs 94-100%, p=0.02). Nine NN patients and two ITC patients were classified as CN-high. Statistics were not applied due to limited numbers. <b>Conclusions:</b> ITCs are associated with less favorable pathologic features than NN disease but are not statistically significantly associated with survival outcomes. Molecular classification type does not have a significant association with the presence of ITCs, but CN-high remains a poor prognostic indicator that may be of clinical value. The role of postoperative therapy in the presence of ITCs or CN-high requires further investigation.