Use of circulating tumor DNA (ctDNA) in the detection of residual disease and recurrence for patients with testicular cancer.

Abstract

620 Background: ctDNA has been increasingly investigated as a biomarker of interest for patients with testicular cancer, a highly curable cancer affecting predominantly young men. Traditional serum tumor markers bHCG, LDH and AFP lack sensitivity and specificity, and have significant variance between patients. While miRNA 371 has emerged as a promising biomarker, it is not applicable in teratoma, has limitations in regards to standardization, and has not been brought to mainstream use. In this study, we evaluate the application of ctDNA in the surveillance of testicular cancer. Methods: Under IRB approval, a retrospective chart review was conducted on patients treated between May 2020 and October 2025 at our academic institution, who had any stage or histology of testicular cancer, with at least one resulted ctDNA value by Natera assay. Results: 41 patients (pts) were included in this study, with a total of 153 ctDNA samples collected. 20/41 (48.8%) of patients had seminoma, and 21/41 (51.2%) had non-seminoma. Age ranged from 20-77, with a median age of 31. 16/41 (39.0%) of patients were White, 15/41 (36.6%) Hispanic, 7/41 (17.1%) Other/Mixed, 2/41 (4.9%) Asian and 1/41 (2.4%) Black. 16/41 (39.0%) of patients had stage I disease, 11/41 (26.8%) had stage II disease, and 14/41 (34.1%) had stage III disease. We calculated a sensitivity of 100% (95% CI 79.4% to 100.0%), and a specificity of 100% (95% CI 97.2% to 100.0%) across all three stages for both residual disease and for relapse, based on 148 ctDNA samples (5 were excluded due to incomplete information). Imaging was used as the gold standard, or pathology, when available. 8/153 ctDNA samples showed discordant ctDNA and imaging, in that either ctDNA rise occurred ahead of detection on imaging, or, positive imaging findings with negative ctDNA, which was validated by negative pathology, suggesting that ctDNA was both more sensitive and specific than imaging. Conclusions: ctDNA is a reliable serum tumor marker in patients with testicular cancer of all stages, and warrants further investigation and validation in larger studies. Its sensitivity and specificity are superior to both that of serum tumor markers (bHCG, LDH and AFP) as well as imaging, and its short half-life relative to that of serum tumor markers makes it a diagnostic tool of practical significance.