There remains an “urgent need” for better therapies, as well as earlier diagnosis and earlier identification of recurrences, in endometrial cancer, according to the authors of a study published in The Oncologist.

The retrospective cohort study, conducted from June 1, 2014 to May 31, 2017, examined clinical and pathologic characteristics tied to endometrial cancer-specific mortality among women at a single National Cancer Institute-designated comprehensive cancer center. All patients with endometrial cancer who underwent a hysterectomy at the center were included. Researchers extracted clinical and demographic data from medical records. They also tested samples for mismatch repair (MMR) proteins using immunohistochemistry and examined clinical-pathologic relationships using χ2, Fisher’s exact test, and t-test.

The study included 771 patients with a mean age at surgery of 61.59. There were fewer patients younger than 60 (N=316; 41%) compared with those aged 60 and older (N=455; 59%). Nearly all patients (N=725; 94%) were White and the mean BMI was 38.02. Most patients had an endometrioid histology (N=632; 82%), stage 1 disease (N=613; 79.5%), and no adjuvant therapy (N=542; 70.3%). MMR status was intact in the majority of patients (N=588; 76.3%).

The investigators analyzed 760 patients with available follow-up data. In total, 76 patients (10%) died due to endometrial cancer or endometrial cancer treatment. Of these, 14 short-term deaths (18.4%) were from endometrial cancer, specifically from rapid disease progression (N=10) and medical comorbidities worsened by surgical recovery (N=4). The remaining mortalities during the study period (N=62) were due to endometrial cancer recurrence. When the researchers examined recurrence death rates according to histologic subtype, they found that women with endometrioid disease had the lowest overall death rate (4%), in “stark contrast” to death rates among those with carcinosarcoma (45.5%) and serous (36.4%) histologies.

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Stage and MMR status also predicted death due to endometrial cancer. Overall, 27.8% of patients with stage III disease died of their recurrence; 51.5% of patients with stage IV disease died of their disease recurrence across all histologies. Conversely, only 2.6% of patients with stage I disease across all histologies died from endometrial cancer. Among patients with endometrioid endometrial cancer, 10.3% of those with MMR-deficient tumors died, compared with 2.1% of those with intact MMR (relative risk [RR], 4.8; 95% CI, 2.3-10.3; P<.0001). More than one-half of endometrioid endometrial cancer deaths (60%) occurred among women with MMR defects, despite MMR deficiency occurring in less than one-quarter of these patients (23.7%). MMR status was not significantly related to death in those with non-endometrioid endometrial cancer.

The study team also assessed treatment among those with endometrial cancer recurrence who died. Most patients (N=51; 82.3%) were treated with adjuvant therapy as part of their initial treatment, almost all of whom (N=46) received chemotherapy with or without radiation. At the time of recurrence, more than one-half of patients (56.5%) received additional treatment. Women who did not undergo treatment at the time of recurrence were older at the time of initial surgery (mean age, 70 vs 65; P=.03).

At the time of data analysis, most patients (85.4%) from the initial pool of 760 individuals with follow-up data had no evidence of disease and no recurrence of endometrial cancer.

According to the researchers, while treatment at the point of recurrence in endometrial cancer improves overall survival, only about one-half of patients will undergo treatment at that point. They also noted that “traditional prognostic features,” such as histology and stage, remain important in predicting recurrence risk, while newer biomarkers—such as MMR status—may improve risk stratification and targeted therapy.