The Past, Present, and Future of ctDNA-Monitoring in Cancer Care

The Best of ASCO Hong Kong 2025, held on July 5, 2025, showcased practice changing clinical data from the ASCO 2025 Annual Meeting. Licensed by ASCO and organized by the Hong Kong International Oncology Research Society in collaboration with ASCO, this one-day event brought together oncology experts to explore advancements in cancer care. With a focus on precision medicine, the program emphasized emerging data on biomarker-driven therapies, immunotherapies, and minimally invasive monitoring tools. A key highlight was a lunch symposium entitled “The Past, Present, and Future of ctDNA-MRD Monitoring in Cancer Management and Beyond” with Professor Feng-Ming (Spring) Kong, Alice Ho Miu Ling Nethersole Charity Foundation, Professor in Holistic Cancer Care, The University of Hong Kong. Her presentation delved into the advancing role of circulating tumour DNA (ctDNA) for minimal residual disease (MRD) detection, response monitoring, and treatment guidance, weaving together historical context, guideline updates, pivotal trials, real-world evidence and visionary prospects. Here, we share key highlights from Professor Kong’s address, emphasizing the scientific progress and optimistic outlook for integrating ctDNA into routine clinical practice. 

A Historical Journey: The Rise of ctDNA

Professor Kong outlined ctDNA’s remarkable evolution, beginning with the discovery of cell-free DNA in human blood 1948, through detection of tumour-specific mutations, such as KRAS in plasma DNA, in the 1990s. She highlighted the rapid acceleration in recent years, driven by technologies like liquid biopsy next generation sequencing platforms. This progression has transformed ctDNA from a research curiosity into a versatile and powerful tool for early detection, MRD assessment, tumour profiling/treatment guidance, response monitoring, across various cancers. 

Professor Kong: “ctDNA’s journey from a laboratory finding to a clinical standard reflects decades of innovation, enabling us to detect and manage cancer with unprecedented precision.” 

ctDNA Today: Shaping Clinical Practice 

Professor Kong emphasised the expanding integration of ctDNA into international guidelines, underscoring its growing acceptance as a reliable biomarker. The Japan Society of Clinical Oncology recommends considering preoperative ctDNA testing for recurrence prediction for solid tumours, based on data and expert consensus. The NCCN 2025 Guidelines recognize ctDNA-MRD as a prognostic marker and high-risk factor in colorectal cancer, a surveillance tool in Merkel cell carcinoma, and an alternative to biopsy for PET-positive results post-first-line therapy in diffuse large B-cell lymphoma. For NSCLC, tissue-based testing remains preferred for stages I-III, but in advanced or metastatic settings, complementary ctDNA and tissue testing enhance the detection of targetable alterations due to high specificity. These updates reflect ctDNA maturation, though Professor Kong noted ongoing challenges like cost and accessibility, with partial reimbursement in some Asian centres signalling progress toward equitable implementation expanding role in clinical decisions. 

Key ASCO 2025 Insights: 

Professor Kong spotlighted several ASCO 2025 studies demonstrating ctDNA’s clinical impact across tumour types, with results that reinforce its prognostic and predictive value while highlighting opportunities for personalized care:  

• Breast Cancer: The SERENA-6 phase III trial, a double-blind study used ctDNA to monitor endocrine resistance, showing improved progression-free survival by switching to camizestrant upon ESR1 mutation detection.  

• Colon Cancer: The DYNAMIC-III trial in stage III colon cancer patients used tumour informed ctDNA to personalize adjuvant therapy – de-escalating for negatives and escalating for positives – yielding recurrence-free survival (RFS) comparable to standard care but with reduced toxicity and costs. 

• Non-Small Cell Lung Cancer: In advanced NSCLC, early ctDNA reductions predicted immunotherapy response, often surpassing imaging accuracy. 

These findings illustrate ctDNA’s versatility in guiding escalation or de-escalation, minimizing overtreatment, and enhancing patient-centered decisions, particularly in resource-limited settings. 

First Real-world Study of ctDNA-MRD Monitoring in Asia 

A major highlight was Asia’s largest real-world ctDNA-MRD monitoring study (Van-Anh Nguyen Hoang et al., 2025), involving over 600 cancer patients using K-TRACK, an affordable tumour informed ctDNA assay combined with comprehensive genomic profiling to predict recurrence in solid tumours. This landmark multicentre study demonstrated strong performance in recurrence prediction and response monitoring across solid tumours.  

• In both early and advanced-stage cancer patients, following surgery 84.4% of patients with ctDNA positive results eventually relapsed, while 96.3% of those with ctDNA negative results remained cancer free  

• Serial testing every 3–6 months detected relapse 5.5-19.5 months earlier than clinical diagnosis by imaging, with 90.3% concordance with confirmed diagnoses helping to resolve ambiguous imaging findings 

• ctDNA-positive patients were retested sooner enabling earlier interventions and underscoring the assay’s high negative predictive value for surveillance  

This study, hypothesis-generating and confirmatory of ASCO data, validates ctDNA’s real-world utility in an Asian population. 

Multi-omic Comprehensive Genomic Profiling and Beyond 

Professor Kong emphasized the power of multi-omics and artificial intelligence (AI) in advancing precision oncology. She highlighted platforms like K-4CARE, a next generation multi-omic assay which integrate ctDNA monitoring with comprehensive genomic and transcriptomic profiling (CGTP). Unlike traditional genomic profiling which may miss rare biomarkers needed to optimize treatment selection and prognosis, CGTP combines DNA and RNA sequencing to cover somatic actionable/resistance/germline mutations, immunotherapy biomarkers such as TMB, MSI, PDL-, oncovirus profiling, tumour tissue of origin for identification for cancers of unknown primary as well as enhanced detection of large indels and genomic rearrangements and with 25% increased sensitivity to detect rare and common fusions. This approach enhances therapy selection, prognosis, real-time monitoring, and improved overall clinical efficiency. 

Professor Kong: “By merging multi-omics and AI with ctDNA monitoring, we can unlock a new era of precision oncology, ensuring personalized care for every patient.” 

Addressing Challenges and Opportunities 

Professor Kong acknowledged practical challenges in ctDNA adoption, notably the high cost of testing (up to $10,000 per test in some centers) and limited reimbursement, which can hinder accessibility, particularly for patients in resource-constrained settings like Hong Kong. She shared poignant examples from Central Hospital, where financial constraints often force patients to forego optimal treatments or opt for less effective alternatives. She noted that while guidelines are evolving positively – such as endorsements by JSCO and NCCN for specific cancers – ctDNA is not yet routinely recommended for MRD, reflecting the need for more comprehensive data. Reproducibility in sensitive areas like proteomics also remains a challenge due to sample quality issues. However, she highlighted promising opportunities to overcome these hurdles. Partial reimbursement in regions like Guangdong, China signals progress toward accessibility. Asia’s leadership in generating vast genomic datasets, positions the region to drive global evidence. Professor Kong called for collaborative trials to substantiate ctDNA’s utility across all cancer stages and types, leveraging Asia’s data richness to inform guidelines. She also emphasized the role of AI driven multi-omic assays to improve reproducibility to bridge healthcare disparities and enhance patient centred care.  

A Holistic Vision for Precision Oncology and Future Directions  

Professor Kong’s presentation underscored ctDNA-MRD and comprehensive genomic and transcriptomic profiling (CGTP) as transformative tools for advancing personalized cancer care by enabling earlier detection, dynamic risk stratification, and tailored treatments. The integration of multi-omics— such as genomics, transcriptomics, epigenomics, proteomics, fragmentomics, and metabolomics—with AI-driven models representing a new cornerstone of precision oncology. By combining ctDNA analysis with radiomics and immune profiling, these approaches enhance prognostic accuracy, uncover resistance mechanisms, and guide personalized interventions across early and advanced disease stages. 

Professor Kong advocated a holistic approach that balances tumor control with preservation of host immunity, emphasizing factors such as immune scores, lymphocyte function, and the systemic tumor microenvironment. This strategy promises sustainable outcomes by prioritizing both cancer eradication and patient resilience. A key advancement she highlighted is the development of neoantigen vaccines, combined with immune-stimulating radiation therapy, which holds significant promise. 

To fully realize ctDNA’s potential, Professor Kong called for prospective validation through randomized controlled trials and meta-analyses to establish its utility in MRD detection, treatment stratification, and neoadjuvant settings for stage shifts at diagnosis. She emphasized redefining study endpoints to prioritize progression-free survival (PFS) alongside quality of life, toxicity reduction, and cost-effectiveness, reflecting modern salvage therapies and patient-centered priorities. Collaborative efforts, including systematic literature reviews and economic evidence generation, are essential to inform guidelines and integrate these tools into clinical practice, particularly for escalation and de-escalation strategies. Asia’s data richness, driven by extensive genomic testing, positions the region to lead these efforts, addressing disparities and accelerating adoption of holistic, AI-supported precision oncology. 

Supported by innovative diagnostic platforms, such as those developed by Gene Solutions, the advancements position Asia’s data-rich genomic research to lead global efforts in reducing the cancer burden and improving patient outcomes through holistic, AI powered precision oncology. For more information, visit genesolutions.com.