Clinical utility of a tumor-naïve circulating tumor DNA (ctDNA) test to predict outcomes in patients with advanced testicular germ cell tumors.

5032 Background: Serum tumor markers (STM) used in the management of Testicular Germ Cell Tumors (TGCT) lack sufficient specificity and are not altered in up to 60% of patients (pts). We evaluated the clinical utility of a tumor-naïve ctDNA test to predict outcomes in pts with advanced TGCT. We also analyzed the correlation between ctDNA detection and STM levels. Methods: Blood samples were collected from 31 pts before and after first-line treatment (chemotherapy, primary radiotherapy or retroperitoneal lymphadenectomy). ctDNA detection was performed using a ddPCR assay to identify copy number gains in chromosome 12p, present in 90% of TGCTs. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier curves and the log-rank test. The correlation between ctDNA status and STM alterations was analyzed using Pearson’s correlation test. Results: The median age of participants was 31 years, 81% were non-seminoma, 48% stage III, 45% IGCCCG intermediate-poor risk, 39% Sx-S0 stage, 83% received first-line chemotherapy, and the median follow-up time was 53 months. The ddPCR assay showed 88% sensitivity and 100% specificity for ctDNA detection. ctDNA detection before first-line treatment significantly correlated with altered LDH levels (r=0.78, p<0.001) but did not correlate with altered AFP (r=0.33, p=0.16) or bHCG levels (r=-0.03, p=0.88). Detection of ctDNA before first-line treatment was significantly associated with a shorter 2-year PFS rate (ctDNA positive 64% vs. ctDNA negative 100%, p=0.022) and 2-year OS rate (ctDNA positive 64% vs. ctDNA negative 100%, p=0.014). None of the patients who tested negative for ctDNA detection experienced disease progression or died. Elevated STM levels before first-line therapy were not significantly associated with PFS (p=0.07) or OS (p=0.053). Detection of ctDNA after first-line therapy did not significantly correlate with PFS (p=0.27) and OS (p=0.29), and was not predictive of viable tumor or teratoma in the surgical specimen. Conclusions: This is the first study to use a tumor-naïve ctDNA test to assess outcomes in pts with TGCT. ctDNA detection before first-line therapy may serve as a valuable prognostic biomarker, complementing STM for pts with advanced TGCT. Further prospective studies are needed to validate our findings.