Association of hormone therapy with long-term outcomes after chemoradiation for locally advanced cervical cancer.

Abstract

Concurrent chemoradiotherapy for locally advanced cervical cancer frequently induces premature menopause in young patients, resulting in long-term metabolic, skeletal, and cardiovascular morbidity. Despite guideline recommendations, hormone therapy remains underutilized because of persistent concerns regarding its safety and potential effects on oncologic outcomes. To evaluate the association of hormone therapy with long-term metabolic, skeletal, cardiovascular, oncologic, and survival outcomes in young patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy. This was a retrospective, multiinstitutional cohort study using a large multinational electronic health record network (TriNetX). The study included women aged<45 years with newly diagnosed International Federation of Gynecology and Obstetrics 2018 stage IIB-IVA cervical cancer who underwent first-line concurrent chemoradiotherapy. To eliminate immortal time bias, we performed a landmark analysis with the index event defined as exactly 1 year following the initiation of chemoradiotherapy. The exposure group included patients who initiated estrogen-based hormone therapy within this 1-year window. Patients who died or developed primary outcomes before the 1-year landmark were excluded. Propensity score matching was performed using absolute standardized mean differences to balance covariates. The matching model included age at the index event, current age, race, body mass index, Charlson Comorbidity Index score, and metastatic sites (para-aortic lymph node, pelvic lymph node, bladder, and colorectal). The primary outcomes included incident type 2 diabetes mellitus, cerebrovascular disease, osteoporosis, compression fracture, thromboembolism, breast cancer, and colorectal cancer. The secondary outcomes included overall survival. Outcomes were assessed using hazard ratios. After propensity score matching, 4656 patients were included (2328 receiving hormone therapy and 2328 not receiving hormone therapy). The median follow-up time was 11.8 years (interquartile range, 7.3 to 17.2) for the hormone therapy group and 11.0 years (interquartile range, 6.6-16.4) for the nonhormone therapy group. Among patients initially classified as nonhormone therapy users, 112 of 2328 (4.8%) subsequently had recorded hormone therapy exposure after the 1-year index event. Cumulative hormone therapy duration and discontinuation during follow-up were not reliably quantifiable in the aggregate platform. Compared with nonhormone therapy users, hormone therapy use was associated with a significantly lower risk of type 2 diabetes mellitus (5.3% vs 9.8%; hazard ratios, 0.59; 95% confidence interval, 0.32-0.81), cerebrovascular events (5.1% vs 8.9%; hazard ratios, .71; 95% confidence interval, 0.39-0.91), and compression fractures (3.1% vs 7.4%; hazard ratios, 0.69; 95% confidence interval, 0.33-0.93). There were no significant differences in incidences of thromboembolism, breast cancer, or colorectal cancer. The use of hormone therapy was also associated with significantly improved overall survival (hormone therapy, 0.81; 95% confidence interval, 0.63-0.91). In this large multinational cohort of young patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy, initiating hormone therapy within the first year was associated with reduced metabolic, skeletal, and cerebrovascular morbidity and improved overall survival, without an increased risk of oncologic outcomes during long-term follow-up. These findings support the safety and potential systemic health benefits of hormone therapy in this undertreated population.