Abstract

Objectives: To assess associations between mismatch repair (MMR) status and recurrence-free survival (RFS) among early-stage endometrial cancer patients with and without isolated tumor cells (ITCs). Methods: We conducted a multi-institution, retrospective study of women with stage I/II endometrial cancer with endometrioid histology who underwent surgical staging with sentinel lymph node (SLN) mapping with or without completing the lymphadenectomy between 2016 and 2021. SLN mapping was performed following the NCCN SLN mapping guidelines. ITC patients and matched controls were identified through electronic medical records using keyword search. Patients were excluded if they had evidence of micro-or macro-metastases in any lymph node (LN). Categorical variables were analyzed using the Chi-square test and continuous variables were analyzed with Student’s t-test and the two-proportion Z-test. Kaplan–Meier method and log-rank tests were used for survival analysis. Results: Among 234 patients, 38 were found to have ITCs. The majority had grade 1 (82.1%), stage IA (67.0%), endometrioid adenocarcinoma. Overall, 22.2% of tumors were MMR deficient by immunohistochemistry. Patients with ITCs were more likely to demonstrate > 50% myometrial invasion (24.5% vs 52.5%, p=<0.001) and were more likely to receive adjuvant radiation therapy (14.8% vs 42.1%, p<0.001) and/or chemotherapy (2.6% vs 23.7%, p<0.001). Grade (p=0.923) and MMR status (p=0.850) were not significantly different between patients with ITCs and those with LN-negative disease. The Median follow-up time was 27 months. Overall, 11 patients we re diagnosed with recurrence (4.7%). The recurrence rate for patients with LN-negative disease was 4.6% (9/196) and the recurrence rate for ITC positive patients was 5.3% (2/38) (p=0.842). The 3-year RFS was 96% in patients with LN-negative disease and 88% in patients with ITC positive disease (log-rank p=0.712). Recurrence rates were comparable among patients with MMR proficient tumors, regardless of ITC status (LN-negative: 3.3% vs ITC-positive: 3.4%; p=0.975). This was also true among patients with MMR deficient tumors (LN-negative: 9.3% vs ITC-positive: 11.1%,p=0.175). RFS was not different between LN-negative and ITC-positive patients with MMR proficient tumors (log-rank p=0.846) as well as between LN-negative and ITC-positive patients with MMR deficient tumors (log-rank p=0.790). Conclusions: These preliminary data suggest that the presence of ITCs does not impact RFS in early-stage endometrial cancer patients with MMR proficient or MMR deficient tumors. However, a longer follow-up time and a larger sample size are needed to better explore the relationship between the presence of ITCs and tumor molecular characterization. Objectives: To assess associations between mismatch repair (MMR) status and recurrence-free survival (RFS) among early-stage endometrial cancer patients with and without isolated tumor cells (ITCs). Methods: We conducted a multi-institution, retrospective study of women with stage I/II endometrial cancer with endometrioid histology who underwent surgical staging with sentinel lymph node (SLN) mapping with or without completing the lymphadenectomy between 2016 and 2021. SLN mapping was performed following the NCCN SLN mapping guidelines. ITC patients and matched controls were identified through electronic medical records using keyword search. Patients were excluded if they had evidence of micro-or macro-metastases in any lymph node (LN). Categorical variables were analyzed using the Chi-square test and continuous variables were analyzed with Student’s t-test and the two-proportion Z-test. Kaplan–Meier method and log-rank tests were used for survival analysis. Results: Among 234 patients, 38 were found to have ITCs. The majority had grade 1 (82.1%), stage IA (67.0%), endometrioid adenocarcinoma. Overall, 22.2% of tumors were MMR deficient by immunohistochemistry. Patients with ITCs were more likely to demonstrate > 50% myometrial invasion (24.5% vs 52.5%, p=<0.001) and were more likely to receive adjuvant radiation therapy (14.8% vs 42.1%, p<0.001) and/or chemotherapy (2.6% vs 23.7%, p<0.001). Grade (p=0.923) and MMR status (p=0.850) were not significantly different between patients with ITCs and those with LN-negative disease. The Median follow-up time was 27 months. Overall, 11 patients we re diagnosed with recurrence (4.7%). The recurrence rate for patients with LN-negative disease was 4.6% (9/196) and the recurrence rate for ITC positive patients was 5.3% (2/38) (p=0.842). The 3-year RFS was 96% in patients with LN-negative disease and 88% in patients with ITC positive disease (log-rank p=0.712). Recurrence rates were comparable among patients with MMR proficient tumors, regardless of ITC status (LN-negative: 3.3% vs ITC-positive: 3.4%; p=0.975). This was also true among patients with MMR deficient tumors (LN-negative: 9.3% vs ITC-positive: 11.1%,p=0.175). RFS was not different between LN-negative and ITC-positive patients with MMR proficient tumors (log-rank p=0.846) as well as between LN-negative and ITC-positive patients with MMR deficient tumors (log-rank p=0.790). Conclusions: These preliminary data suggest that the presence of ITCs does not impact RFS in early-stage endometrial cancer patients with MMR proficient or MMR deficient tumors. However, a longer follow-up time and a larger sample size are needed to better explore the relationship between the presence of ITCs and tumor molecular characterization.

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