ctDNA emerges as a promising biomarker for event-free survival in patients with testicular cancer
Serum-based tumour markers (STM) lack sufficient sensitivity and specificity for the detection of molecular residual disease (MRD) in patients with testicular cancer. To address this medical need, this study evaluated the utility of longitudinal circulating tumour (ct)DNA monitoring for MRD detection in these patients. The results show a significant association between ctDNA status and event-free survival (EFS) during both the MRD and surveillance windows, suggesting that ctDNA holds promise as a potential biomarker for EFS in individuals with testicular cancer.
Serum-based tumour markers (STM), such as aFP, LDH, and b-hCG, are used as a standard of care in patients with testicular cancer. Despite their widespread use, these markers lack sufficient sensitivity and specificity for the detection of molecular residual disease (MRD). While circulating tumour (ct) DNA holds promise as a prognostic biomarker in a variety of malignancies, its clinical utility in testicular cancer has not yet been well-characterised. This study evaluates the utility of longitudinal ctDNA monitoring for MRD detection in patients with testicular cancer.
Methods
Longitudinal ctDNA testing was performed using a personalised, tumour-informed ctDNA assay (SignateraTM bespoke mPCR-NGS assay). ctDNA was evaluated during the MRD (1-12 weeks post-orchiectomy) and surveillance (>12 weeks post-orchiectomy, post-adjuvant chemotherapy [ACT], or after retroperitoneal lymph node dissection [RPLND]) windows. The correlation between ctDNA status and patient outcomes (event-free survival [EFS]) was assessed. EFS was defined as the interval from radical orchiectomy to the date of radiological recurrence or any evidence of residual/persistent disease after the completion of ACT or RPLND.
Results
A total of 145 plasma samples were collected from 35 patients with stage I-III testicular cancer. Median age of the patients was 34 years. The majority of patients had stage I disease (66%), with 23% and 11% presenting with stage II and III, respectively. Additionally, 49% and 51% of patients were classified as having seminoma and non-seminoma, respectively. The median follow-up was 10 months.
In the pre-orchiectomy window (n=15), ctDNA was detected in 11/12 patients with stage I (91.6%), and 3/3 patients with stages II/III (100%). In the MRD window (n=22), ctDNA was detected in 2/4 (50%) and 3/3 (100%) patients with stages II and III, respectively. Interestingly, none of the patients with stage I had detected ctDNA in this window (0/15). Comparable results were observed in the surveillance window (n=27), with 1/21 patients with detected ctDNA in stage I (4.8%), 2/5 in stage II (40%) and one in stage III (100%).
During the MRD window, patients who tested ctDNA positive showed a significantly inferior EFS compared to those who tested negative (HR[95%CI]: 7.21[1.42-36.69], p= 0.017). The 12-month EFS rates were 76.5% vs. 25% for ctDNA negative and positive patients, respectively. A similar trend was observed during the surveillance window (n=27), where patients with positive ctDNA displayed a significantly inferior EFS compared to those with negative ctDNA (HR[95%CI]: 11.75[2.34-59.09], p= 0.003).
Subsequently, the association between ctDNA and STM was evaluated. Notably, all patients with ctDNA positive signal (n=3) relapsed, even if two of them had normal STM. Among patients with ctDNA negative results and normal STMs, 3 out of 19 also faced relapse. Examining the connection between ctDNA and RPLND, ctDNA was positive in two cases where a viable tumour was present. However, its current limitations include the inability to effectively identify patients with teratoma.
Conclusions
These findings represent pioneering results, employing longitudinal tumour-informed ctDNA testing to evaluate patient outcomes and disease status in individuals with testicular cancer. The results show a significant association between ctDNA status and EFS during both the MRD and surveillance windows. Future prospect studies would be needed to further assess the utility of ctDNA in patients with testicular cancer.
Reference
Ben-David R, Chehrazi-Raffle A, Laliotis G, et al. Longitudinal tumor-informed ctDNA assay and patient outcomes in testicular cancer. Presented at ASCO GU 2024; Abstract 499.
