Circulating Tumor DNA Analysis in Adrenocortical Carcinoma: A Retrospective Cohort Study

Adrenocortical carcinoma (ACC) is a rare malignancy with high recurrence rates. Circulating tumor DNA (ctDNA) is a minimally invasive, blood-based biomarker with multiple oncologic applications. The role of ctDNA in ACC care remains understudied. This retrospective, single-institution, study evaluated real-world use of ctDNA testing in patients with ACC and its correlation with imaging-based tumor burden. Patients with ACC (≥ 18 years) who underwent ctDNA testing via a clinically validated, personalized, tumor-informed assay (Signatera™, Natera) during their disease course were reviewed, and clinical data were obtained from the medical records. ctDNA results were tested for association with disease status and tumor burden determined by concurrent imaging and clinical evaluation. Twenty patients (55% male) were included; the median age at first ctDNA assessment was 58.3 years (range, 23.3-81.1). A total of 87 ctDNA tests were analyzed (median, 4 tests/patient; interquartile range [IQR], 1-6). The median ctDNA level was 1.27 mean tumor molecules/mL (IQR, 0.05-22.86). Detected ctDNA was strongly associated with evidence of disease (odds ratio, 74; 95% confidence interval, 9-3438). The ctDNA assay demonstrated high sensitivity (88%), specificity (91.7%), and overall accuracy (88.5%), with a positive post-test probability of 98% and a negative post-test probability of 45%. In addition, ctDNA levels were positively correlated with tumor burden (Spearman R = 0.844; p < 0.001). These findings support the potential value of ctDNA testing for disease monitoring in ACC and it may support a more personalized approach to this rare disease.