29 Low-grade endometrioid endometrial cancer with adnexal metastasis: possible de-escalation candidate for adjuvant therapy?

According to the National Comprehensive Cancer Network clinical practice guidelines, patients with stage III endometrioid endometrial cancer are recommended to receive combination therapy with systemic chemotherapy and external beam radiotherapy. Mounting translational data proposed a concept of “restricted microenvironmental compatibility” in low-grade endometrioid endometrial cancer. In this theory, low-grade endometrioid tumors are indolent and further distant metastasis beyond the ovary is biologically limited. We hypothesized that this tumor group has good oncologic outcomes even after metastasis to the ovary. The objective of current study was to examine the association between adjuvant therapy and oncologic outcomes of patients with low-grade endometrioid endometrial cancer with metastasis to the adnexa. We retrospectively queried the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population was stage IIIA grade 1–2 endometrioid endometrial cancer with ovarian or tubal metastasis only who received adjuvant therapy from 2010–2015. Patients with uterine serosal disease, nodal involvement, distant metastasis, and secondary primary cancer were excluded. The exposure was adjuvant therapy, grouped as systemic chemotherapy without external beam radiotherapy (EBRT), EBRT alone, and combination of the two. The outcome measure was endometrial cancer-specific survival. Cox proportional hazard regression model was fitted to assess the exposure-outcome association, adjusting for patient age and tumor differentiation. A total of 245 patients were evaluated. The most frequent adjuvant therapy was systemic chemotherapy alone (46.1%), followed by combination of systemic chemotherapy and EBRT (42.0%) and EBRT alone (11.8%). The median follow-up was 6.4 (IQR 5–7.8) years. The 5-year endometrial cancer-specific survival rates were 93.3% for systemic chemotherapy alone, 92.9% for EBRT alone, and 91.0% for combination therapy (P=0.963). After controlling for patient age and tumor differentiation, combination therapy (adjusted-hazard ratio 0.83, 95% confidence interval 0.36–1.89) and EBRT alone (adjusted-hazard ratio 0.86, 95% confidence interval 0.24–3.15) were not associated with endometrial cancer-specific mortality compared to systemic chemotherapy alone. This association remained robust in sensitivity analyses for grade 1 (5-year endometrial cancer-specific survival rates for systemic chemotherapy alone, EBRT alone, and both: 95.9%, 100%, and 94.9%, respectively, P=0.618) and grade 2 (91.1%, 84.6%, and 88.6%, respectively, P=0.725) lesions. Download : Download high-res image (68KB)Download : Download full-size image These results suggest that patients with low-grade endometrioid endometrial cancer with metastases to the adnexa alone have a favorable prognosis. In this cohort combination therapy may not improve oncologic outcome compared to systemic chemotherapy alone.