Longitudinal evaluation of circulating tumor DNA (ctDNA) as a prognostic biomarker to detect minimal residual disease (MRD) in testicular cancer.
Authors: Hassoun Rebecca , Ben-David Reuben , Sfakianos John P. , Laliotis George , Cary Clint , Masterson Timothy A. , Rivero-Hinojosa Samuel , Manage Kevin , Dutta Punashi , Tillu Neeraja , Cumarasamy Shivaram , King Jennifer , Rich Jordan , Rock Adam , Dorff Tanya B. , ElNaggar Adam , Liu Minetta C. , Einhorn Lawrence H. , Chehrazi-Raffle Alex , Adra Nabil 
Published: June 2024

5034

Background: Serum tumor markers (STM) (AFP, hCG) are currently utilized in the management of patients (pts) with testicular cancer. However, in a substantial proportion of pts STM can be normal or falsely elevated. We evaluated the clinical utility of longitudinal ctDNA monitoring as a prognostic marker in pts with testicular cancer. Methods: Longitudinal analysis was performed on a multi-institutional cohort of pts with stages I-III testicular cancer using a clinically validated, personalized, tumor-informed 16-plex PCR ctDNA assay (Signatera, Natera Inc.). ctDNA was evaluated pre-orchiectomy, during the MRD (1-12 weeks post-orchiectomy) and surveillance windows (>12 weeks post-orchiectomy, after retroperitoneal lymph node dissection [RPLND], and/or chemotherapy). The correlation between ctDNA status and event-free survival (EFS) was assessed. EFS is described as the interval from orchiectomy to the date of radiological recurrence or any evidence of residual/persistent disease post-completion of chemotherapy or RPLND. This analysis includes 28 pts from Icahn School of Medicine, 20 pts from Indiana University, and 7 pts from City of Hope. Results: Plasma samples (n=197) were collected from 55 pts - %stage I/II/III: 42/22/36; %seminoma/non-seminoma: 31/69. The median age was 34 years (range: 16-67), and the median follow-up was 11 months (range: 2-76). Disease management post-orchiectomy included surveillance in 27% (15/55), RPLND in 11% (6/55), chemotherapy in 40% (22/55), and chemotherapy+RPLND in 22% (12/55) of the pts. Pre-orchiectomy ctDNA was detectable in 14/15 pts - 91.6% (11/12) of pts with stage I, and 100% (3/3) of pts with stage II/III disease. ctDNA evaluation pre-RPLND (N=7; 1 seminoma, 6 non-seminoma) revealed ctDNA-positivity in 6 pts. Six pts had ctDNA testing performed pre- and post-completion of chemotherapy for stage II/III disease; ctDNA exhibited a median MTM/mL reduction of 96.5% (range: 75.6–100) post-treatment completion. Seventeen pts had ctDNA testing post-RPLND or chemotherapy; 0/9 pts with undetectable ctDNA relapsed while 4/8 pts with detectable ctDNA experienced clinical recurrence at the most recent evaluation with follow-up ongoing. During the MRD (N=27) and surveillance (N=36) windows, pts with detectable vs. undetectable ctDNA showed a significantly inferior EFS (MRD: HR= 5.27, 95% CI: 1.22-22.71; p=0.026. Surveillance: HR= 10.8, 95% CI: 2.53-46.01; p=0.001). During the surveillance window, elevated STM vs. normal STM was not associated significantly with worse EFS (HR= 2.01, 95%Cl: 0.71-5.72; p=0.191). Conclusions: Tumor-informed ctDNA analysis shows promise for MRD detection in pts with testicular cancer. With further study, ctDNA monitoring may have utility in clinical decision-making. Larger prospective trials are planned for validation of clinical utility.