Subclinical hepatic injury and risk of nonalcoholic steatohepatitis after adjuvant systemic therapy in early-stage testicular cancer survivors.

Abstract

607 Background: Patients with early-stage TGCT have an excellent long-term prognosis. Guidelines recommend active surveillance (AS) or adjuvant chemotherapy (CT) or radiation therapy for patients with high-risk features. However, long-term treatment-related toxicities are an increasing concern, especially with a rise in cardiometabolic disease. Subclinical hepatic injury leading to non-alcoholic steatohepatitis is an underreported complication. We aim to evaluate the impact of adjuvant systemic therapy on liver function in early-stage TGCT survivors. Methods: We conducted a retrospective cohort study of consecutive patients with clinical stage I and IIa testicular germ cell tumors treated at a tertiary care center in Mexico between 2015 and 2024. Patients who received adjuvant systemic therapy were compared with those managed through active surveillance. Hepatic injury was assessed using the non-invasive FIB-4 (Fibrosis-4) and APRI (AST-to-Platelet Ratio Index) scores, which estimate the extent of liver fibrosis based on routine biochemical and hematologic parameters. Both scores were calculated at diagnosis and at the last follow-up. Changes in metabolic syndrome components, including overweight or obesity, hypertension, dyslipidemia, and insulin resistance, were analyzed. Statistical analysis was conducted using chi-square tests and Student’s t-tests to determine differences between groups. A linear regression model was employed to identify predictive factors. Statistical significance was determined using both a p-value <0.05. Results: We included 142 eligible patients. Most were managed with AS (N = 96, 68%), while 46 received systemic adjuvant treatment (32%). The mean age at diagnosis was higher in the adjuvant group (31.4 ± 7.7 vs. 28.5 ± 8.7 years, p = 0.049), with similar distributions of smoking status and clinical stage between the groups. Seminoma histology was more common among patients receiving adjuvant therapy (76.1% vs. 43.8%, p = 0.001). In multivariable analysis, adjuvant therapy was independently associated with increases in FIB4 score (β = 0.18, 95% CI 0.05–0.32, p = 0.009) and APRI score (β = 0.10, 95% CI 0.02–0.18, p = 0.019) at follow-up, after adjusting for baseline values. There was a clear trend toward a higher prevalence of metabolic syndrome risk factors, particularly overweight and dyslipidemia, in the AS and adjuvant CT groups, although these associations did not reach statistical significance in the regression analysis. Conclusions: Exposure to adjuvant systemic therapy seems to be an independent risk factor for long-term subclinical hepatic injury in survivors of early-stage TGCT. The observed metabolic changes also merit clinical attention. These results could support integrating non-invasive screening methods like FIB-4 and APRI for long-term follow-up.