Lymph node metastases in endometrial carcinoma: A modern assessment in the era of sentinel lymph node mapping and molecular subtyping

Objective. To examine the risk of sentinel lymph node (SLN) metastases in apparent uterine-confined endometrial cancer (EC) using molecular classification with clinicopathologic features and assess oncologic outcomes by molecular subtypes with micro- or macro-metastases in SLN. Methods. Patients undergoing surgical staging for presumed uterine-confined EC of any histology, with successful bilateral SLN mapping were included. Primary tumors were assigned molecular subtypes using a published algorithm. SLN pathology was categorized as negative, isolated tumor cells (ITCs), or micro- or macro-metastases. Results . Overall, 756 patients were included; 80 (10 %) had micro- or macro-metastases and 51 (7 %) had ITCs. On multivariate multinomial logistic regression, risk of micro- or macro-metastases versus negative SLN was higher for ECs with copy number-high (CN-H)/TP53abn (OR 3.1; 95 % CI 1.3-7), lymphovascular space invasion ([LVSI]; OR 8.0; 95 % CI 4-16), and deep myoinvasion (>= 50 %; OR 3.33; 95 % CI 1.9-6.04). Three-year PFS rates by subtype for 68 patients with macro-metastases were 38 % (95 % CI 10-67 %) CN-low/no specific molecular subtype (CN-L/NSMP), 66 % (95 % CI 44-82 %) microsatellite instability-high (MSI-H), and 23 % (95 % CI 10-40 %) CN-H/TP53abn (p = 0.006). Three-year OS rates were 55 % (95 % CI 20-80 %) CN-L/NSMP, 83 % (95 % CI 61-93 %) MSI-H, and 55 % (95 % CI 34-71 %) CN-H/TP53abn (p = 0.048). Conclusions. Integrating molecular subtype with uterine risk factors (LVSI and myoinvasion) further stratifies risk of occult SLN metastases in patients undergoing surgical staging for early-stage EC. No molecular subgroup had exceedingly low SLN metastases detected, supporting continued universal SLN assessment. Patients with macro-metastases and CN-L/NSMP or CN-H/TP53abn EC had worse outcomes than those with MSI-H EC.