Recurrence After Surgery for Stage II Endometrial Cancer Leads to Limited Survival: Practice Patterns and Outcomes of Adjuvant Treatment in an Integrated Healthcare System

Abstract

Though increased risk of locoregional recurrence in intermediate-risk endometrial cancer warrants adjuvant treatment, the type and extent of therapy for FIGO Stage II disease is not well-standardized. Here, we observe practice patterns and outcomes for such patients in our integrated healthcare system. All incident cases of endometrioid adenocarcinoma diagnosed 2010-2017 were identified by central cancer registry. Patients who underwent definitive surgery and had pathological Stage II disease (cervical stromal invasion without extrauterine involvement) were included. Clinical data were obtained by electronic medical record abstraction. Gastrointestinal (GI) and genitourinary (GU) toxicities were graded by CTCAE 5.0. Of 4317 cases identified, 119 patients were eligible for analysis. Median age at diagnosis was 61 years. Median follow-up was 50.4 months (IQR 33.4-83.7). Nodal dissection was performed in 61% of patients with 14 median nodes (range 1-45) identified. Pathological grade was 1 in 55 (46%), 2 in 48 (40%), and 3 in 16 (13%). Lymphovascular invasion was seen in 39 (33%). No adjuvant treatment was given to 27 patients (23%). Pelvic external beam radiotherapy (EBRT) alone was administered to 10 patients (8%), vaginal brachytherapy (VBT) alone to 10 (8%), and both to 72 (61%). The most common EBRT and VBT doses were 4500cGy (range 4140-5040) and 2100cGy (range 1200-2100), respectively. Adjuvant chemotherapy only was given to 7 patients (6%), and with radiation to 6 patients (5%). Late grade 2 GI or GU radiation toxicity was experienced by 4 patients (4%); 2 developed late small bowel obstruction. Recurrences were noted in 23 patients (19%): locoregional in 9, distant in 14. Of locoregional recurrences, 6 were after no radiation and 3 after EBRT; 4 failed at the cuff, 4 in the para-aortic nodes, and 1 in the pelvic nodes, leading to 3 deaths. Of distant recurrences, 5 were in the lung and 5 in the omentum. Of 16 patients with grade 3 tumors, 5 recurred distantly and all died of disease; of these, 2 received 3 and 6 cycles adjuvant chemotherapy each. Median time to death was 4.9 months (range 3.5-26.8). At time of analysis, 98 patients were alive (82%) and 21 (18%) had died, 14 of cancer-related causes. Median time from diagnosis to death overall was 27.3 months (range 6.5 – 50.5); median time from recurrence to death was 9.6 months (range 1.3 – 37.1). Most Stage II patients received adjuvant radiation and tolerated it well with few late effects. While locoregional recurrences were uncommon among those receiving radiation, any recurrence led to limited survival among the majority, particularly in those with distant recurrences. As nearly one-third of patients with grade 3 disease developed distant disease, further study is merited in this group which may benefit from systemic therapy.