Does Clinical and Biochemical Thyroid Dysfunction Impact on Endometrial Cancer Survival Outcomes? A Prospective Database Study

Endometrial cancer is the most common gynaecological cancer in high-income countries. Most women are diagnosed early and have an excellent prognosis, but those with advanced or recurrent disease have poor outcomes. The aim of this study was to determine whether clinical or biochemical thyroid dysfunction may contribute to survival outcomes following diagnosis and treatment for endometrial cancer. We analysed clinical data and serum thyroid hormone status of 333 women treated for endometrial cancer at a specialist cancer centre and followed up for a median of 35 months. Women with a diagnosis of hypothyroidism had improved overall, cancer-specific, and recurrence-free survival compared to those without. This may have important implications for our understanding of the mechanisms underpinning biologically aggressive disease and offer opportunities for therapeutic intervention. Endometrial cancer is the commonest gynaecological malignancy in developed countries, and women presenting with high risk or advanced disease have poor outcomes. Thyroid hormones play a key role in cellular metabolism and can influence cancer growth and invasion. Our aim was to evaluate the association between clinical and biochemical thyroid dysfunction and endometrial cancer survival outcomes. This was a prospective cohort study of women treated for endometrial cancer at a specialist centre. Clinical diagnosis of hypothyroidism was based on clinical and biochemical assessment, verified by general practitioner (GP) records. Pre-treatment serum samples were tested for thyrotropin (TSH), thyroid hormones (free T4 and total T3), and thyroid peroxidase antibodies. Kaplan-Meier survival estimates and log-rank tests were used to compare survival between groups, while Cox regression was used for multivariable analysis, adjusting for known confounders and effect modifications. In total, 333 women with median age and body mass index (BMI) of 66 years (interquartile range (IQR) 56, 73) and 33 kg/m(2) (IQR 27, 41) respectively were included. A total of 51 (15.3%) women had a diagnosis of hypothyroidism, 39 (11.9%) had biochemical evidence of overt or subclinical hypothyroidism. Median follow-up was 35 months (IQR 21, 45) with 38 (11.7%) relapses and 50 (15.0%) deaths. Women with a diagnosis of hypothyroidism had improved overall survival (adjusted HR = 0.22, 95%CI 0.06-0.74, p = 0.02), cancer-specific survival (adjusted HR = 0.21, 95%CI 0.05-0.98, p = 0.04) and fewer recurrences (adjusted HR = 0.17, 95%CI 0.04-0.77, p = 0.02) than those who did not. Confirmatory studies should explore underlying mechanisms and the potential for therapeutic exploitation.