Patterns of Care and Outcomes of Adjuvant Treatment in Stage II Endometrioid Carcinoma

Abstract

GOG 249 reaffirmed adjuvant pelvic radiation as the standard of care for high-risk early stage endometrial cancer. Patients with Stage II disease, elderly patients, and patients with poor performance status were underrepresented in the trial population. We utilized the National Cancer Database to study the patterns of care in stage II patients stratified by adjuvant therapy (AT), age, and performance status. We included patients diagnosed in 2004-2014 with stage II (FIGO 2009) endometrioid carcinoma who underwent TAH/BSO with negative margins. Patients with unknown AT, refusing AT, who died after surgery, or who did not have AT because of comorbidity were excluded. All patients with PXRT received a minimum dose of 45Gy and all patients with chemotherapy had multiagent chemotherapy (mCT). Adjuvant therapies compared were surgery alone, mCT alone, VBT alone, PXRT alone, VBT+mCT, PXRT+VBT, PXRT+VBT+mCT. Multivariate Cox regression was used to identify factors significantly associated with overall survival. A total of 5,130 patients were identified with tumor grades 42% G1, 29% G2, 18% G3, and 13% unknown. Lymphovascular invasion (LVI) was present in a small number of patients (14.5%, absent 34.1%, unknown 51.5%). Approximately one quarter of patients were >70 years old (1,232; 24%) and had 1+ comorbidity (1,341; 26%). More than one in four patients (1,492; 29%) did not receive any planned adjuvant therapy. These patients were older >65 (49% vs. 38%), Medicare insured (47% vs 39%), had 1+ comorbidity (31% vs.24%), and lived >50 miles from a treating facility (19% vs 12 %). For adjuvant therapy, 1,231 (24%) had VBT alone, 1,231 (23.5%) PXRT+VBT, 886 (13%) PXRT alone, 140 (3%) mCT alone, and 137 (3%) PXRT+VBT+mCT. The use of mCT+ VBT tripled from 1.8% prior to 2009 to 6.2% after 2009, while PXRT+VBT decreased from 28% to 20.5% in the same time period (all p < 0.001). For the entire cohort, median follow-up was 58.7 mos (95% CI: 57.1–60.1 mos) and 5-yr OS was 79.5% (78.2–80.9%). By adjuvant treatment 5-yr OS was 87.4% VBT+mCT, 84.3% VBT alone, 83.3%, PXRT+VBT, 79.9% PXRT+VBT+mCT, 79.6% mCT, 78.1% PXRT alone, 72.2% surgery alone. On adjusted multivariate survival models, mCT+VBT was not associated with improved OS over PXRT+VBT (adjusted HR 0.68, p=0.1). All adjuvant regimens had a significant survival advantage when compared to surgery alone except mCT alone. In subgroup of elderly patients >70 years and the subgroup of patients with 1+ comorbidity, 35% and 31% patients respectively had no planned adjuvant therapy. These patients had significantly inferior OS compared to patients with AT (elderly: aHR 1.8 (1.5-2.2), p < 0.001; 1+ comorbidity aHR 2.0 (1.6-2.6), p<0.001). Adjuvant treatment for stage II endometrioid carcinoma is not administered to more than one quarter of patients in this national hospital-based. Patients without adjuvant treatment are older and have comorbidities. There appears to be survival benefit to adjuvant treatment in these populations.