Tumor-Informed ctDNA Analysis as a Biomarker for Event-Free Survival in Testicular Cancer

For patients with testicular cancer, the current standard of care is serum-based tumor markers (STMs). However, the method does not provide enough sensitivity and specificity for the detection of molecular residual disease (MRD).

A study led by Reuben Ben-David, MD, and presented at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium sought to determine the benefits of longitudinal circulating tumor DNA (ctDNA) monitoring for MRD detection in testicular cancer.

The retrospective analysis evaluated 145 plasma samples from 35 patients with stage I, II, and III (66%, 23%, and 11%, respectively) testicular cancer. Prior to orchiectomy, researchers observed ctDNA in 91.6% of patients with stage I disease and 100% of patients with stage II or III disease.

Of the patients, 43.0% were on surveillance postoperatively, 23.0% received postoperative adjuvant chemotherapy (ACT), 8.6% underwent retroperitoneal lymph node dissection (RPLND), and 26.0% underwent both ACT and RPLND.

The median follow-up was 10 months, and the median patient age was 34 years.

Patients who tested ctDNA positive experienced significantly inferior event-free survival (EFS) when compared with those who were ctDNA negative in both the MRD (hazard ratio [HR], 7.2; 95% CI, 1.4-36.7; P=.017) and surveillance windows (HR, 11.8; 95% CI, 2.3-59.1; P=.003).

According to multivariate regression analysis, when compared with clinicopathological features like age, stage, histology, and elevated STMs, ctDNA-positive patients experienced poor EFS (P=.015) during surveillance.

Dr. Ben-David and colleagues concluded that ctDNA analysis may benefit patients with testicular cancer. They noted that their study was the first to conduct longitudinal tumor-informed ctDNA testing when assessing patient outcomes and disease status.

“Our results suggest that tumor-informed ctDNA analysis may hold promise as a biomarker for EFS in patients with testicular cancer,” the researchers wrote. “As such, we developed the first-ever clinical nomogram that includes ctDNA status and other clinicopathological factors to stratify patient outcomes.”