Cancer Res Treat.  2023 Jul;55(3):969-977. 10.4143/crt.2022.1557.

Early Plasma Circulating Tumor DNA as a Potential Biomarker of Disease Recurrence in Non-metastatic Prostate Cancer

• Fei X
• Du X
• Gong Y
• Liu J
• Fan L
• Wang J
• Wang Y
• Zhu Y
• Pan J
• Dong B
• Xue W

• KMID: 2544177
• DOI: http://doi.org/10.4143/crt.2022.1557

Abstract

Purpose
In non-metastatic prostate cancer (nmPCa) setting, it is important to early identify the patients at risk of biochemical recurrence (BCR) for immediate postoperative intervention. Our study aimed to evaluate the potential clinical utility of circulating tumor DNA (ctDNA) for predicting disease recurrence.
Materials and Methods
This real-world observational study evaluated 161 cases of nmPCa undergoing next-generation sequencing at our institution. A total of 139 ctDNA samples and 31 biopsied tumor tissue underwent genomic profiling. The study endpoint was BCR after radical prostatectomy. Relationships between the ctDNA status and the biochemical progression-free survival (bPFS) were analyzed by log-rank test and multivariate Cox regression.
Results
Of 161 enrolled patients, 19 (11.8%) harbored deleterious alterations in NCOR2, followed by BRCA2 (3.7%), ATR (2.5%), and CDK12 (2.5%). Of available pre-operative blood samples (n=139), ctDNA was detectable in 91 (65.5%). Until last follow-up, 56 of 68 patients (85.3%) with detectable ctDNA had achieved BCR, whereas only eight of 39 patients (20.5%) with undetectable ctDNA had achieved BCR. Patients who had undetectable ctDNA experienced significantly longer bPFS compared with those who had detectable ctDNA (not available vs. 8.2 months; hazard ratio, 0.14; p < 0.01). Pre-operative ctDNA status was a significant prognostic factor of disease recurrence.
Conclusion
Pre-operative ctDNA detection could identify patients at high risk of recurrence and has the potential to inform immediate postoperative interventions, but these approaches remain to be validated in prospective studies. ctDNA studies can provide insights into accurate monitoring and precise treatment rather than simply following routine clinical care.

Keyword

Circulating tumor DNA; Prostatic neoplasms; Biomarkers

Figure

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  Fig. 1 The schema of the study. ctDNA, circulating tumor DNA; nmPCa, non-metastatic prostate cancer.

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  Fig. 2 The genomic profiles of the studied patients. (A) The genomic landscape of the studied patients. Each column represents alterations detected in individual sample. Upper track shows circulating tumor DNA (ctDNA) fractions. Frequencies of specific gene alterations are displayed on the right side. The color represents copy number variant, missense mutation, frame shift indel, nonsense mutation, splice and germline alteration. Cases with multiple variants in one gene are represented by split colors. (B) The somatic alteration count of ctDNA and matched tumor tissue samples in nine patients. (C) The comparison of the alteration frequencies between the patients with non-metastatic prostate cancer (PCa) and the patients with metastatic PCa. mCRPC, metastatic castration-resistant PCa; mCSPC, metastatic castration-sensitive PCa.

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  Fig. 3 Circulating tumor DNA (ctDNA) status and clinical outcomes. (A) The overview of the studied patients according to the time to biochemical recurrence (BCR) and ctDNA status. (B) Kaplan-Meier curves for time to BCR of the patients with detectable ctDNA and with undetectable ctDNA. (C) Kaplan-Meier curves for time to BCR of the patients with and without pathogenic alterations.

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  Fig. 4 The association between circulating tumor DNA (ctDNA) status and biochemical progression-free survival (bPFS). Kaplan-Meier curves for time to biochemical recurrence of the patients with detectable ctDNA and with undetectable ctDNA according to clinical T category (A, B) and clinical N category (C, D).

Reference

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