Leading causes of death after a diagnosis of endometrial cancer: a systematic review and meta-analysis

Objective: Despite curative treatment, an endometrial cancer (EC) diagnosis is associated with an elevated risk of death compared with age-matched women in the general population. This study aimed to quantify their risk of death from EC, cardiovascular disease, and other causes. Methods: A systematic review of Medline, Embase, and CENTRAL databases was performed to February 2024. Studies reporting cause of death after a diagnosis of EC were included. Mortality rates and 95% CIs were calculated using a random-effects model. Heterogeneity was assessed through visual inspection of forest plots and the I2 statistic. Risk of bias and evidence quality were appraised using the Newcastle-Ottawa scale and Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. The effect of ethnicity, stage, grade, and time from diagnosis was examined. Results: In total, 22 studies including 323,551 participants were analyzed and 102,711 (31.7%) died within 20 years of diagnosis, 62.6% (n = 64,155) from non-EC causes. In the 12 studies that reported cardiovascular death, 24.6% of participants (n = 24,309) died from cardiovascular disease. Those with local disease at presentation were more likely to die from non-EC causes than those with advanced disease at presentation (48.9% vs 13.5%). A total of 2 studies reported cause of death by ethnicity; overall, Black individuals were more likely to die than individuals of White or Other ethnicities (40.8% vs 27.9% vs 18.9%). Deaths related to non-EC causes, including cardiovascular disease, overtook EC-specific deaths >5 years after diagnosis. Significant heterogeneity was noted, despite sub-group analyses, and the findings were based on very low certainty evidence. Conclusions: Individuals with a history of EC are at increased risk of death from other causes. Oncology follow-up appointments provide the ideal opportunity to optimize cardiovascular research needs to reflect the global majority.