Editor’s note: With the rapid evolution of next-generation sequencing (NGS) technologies in recent years, liquid biopsy has become a practical tool for prostate cancer assessment. It enables earlier detection and intervention, while simultaneously identifying actionable mutations for precision therapy. At the 2025 European Society for Medical Oncology Asia (ESMO Asia) Congress, research from Professor Darren Poon’s team at Hong Kong’s Hong Kong Sanatorium & Hospital was selected for presentation, offering new strategic insights for advanced prostate cancer management. UroStream invited Professor Poon to share real-time perspectives from the conference on the clinical value and future applications of liquid biopsy in Chinese patients with androgen receptor ligand-binding domain (AR-LBD) mutated prostate cancer.
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Oncology Frontier- UroStream: Compared to traditional tumor tissue biopsies, what are the main technical challenges overcome by liquid biopsy-based analysis? What are its advantages in analyzing tumor heterogeneity and dynamically monitoring gene evolution?
Dr. Darren M. Poon: The first challenges for the liquid biopsy or the liquid NGS for the metastatic prostate cancer would be the false negative possibilities. Because if you compare the tissue biopsy, you can really get a tissue and send for the NGS testing, whereas for the blood or the liquid NGS, it really depends on the patient’s tumor load as well as the blood that drawn for the NGS, whether that consists of sufficient DNA contents for the analysis. So the possibilities of false negative is one of the challenges for liquid biopsy.
The second challenges will be the differentiation between the mutations versus clonal hematopoiesis for that particular mutations, because sometimes the genetic mutations that detected in the liquid NGS may be arising from the clonal hematopoiesis, especially for the mutations that are related to the DNA repair pathway. So far most of the NGS testing is difficult to differentiate such differences, so that may also affect the therapeutic implications, because if it is really a clonal hematopoiesis mutation, the targeted therapy that add on that mutation may not be very effective compared to the mutations that really arising from that particular tumor.
But the liquid NGS has a very important and advantages that is much easier, and it can take the blood very easily for the liquid NGS, and also you can monitor the dynamic changes for the mutational profile for that particular prostate cancer patients. Because we have some data suggested that the mutations may be evolving with time, and also some of the new targeted such as the androgen receptor ligand binding domain mutations may be happen with a later lines of therapies, because these mutations may be happen with a more systemic therapies they keep evolving. So liquid NGS could help for the monitoring of these dynamic mutational profiling changes.
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Oncology Frontier- UroStream: For patients with detected AR LBD mutations, what factors should clinicians focus on when developing treatment strategies?
Dr. Darren M. Poon: The importance of detecting the androgen receptor ligand binding domain mutations is because we have some data to suggest with the presence of these mutations, the patients may have a poor prognosis, and the response to the androgen receptor pathway inhibitors may be affected when these mutation occur. And nowadays we looking forward for new targeted therapy focusing on these patients with AR LBD mutations. One of the potential targeted therapy is the Opifovestat, which is a CYP11A1 inhibitor, and then it will cut down the testosterone and also the subsequent all the androgen productions. And from the phase 2 trials that has been presented in ESMO last year for patients with these AR LBD mutations, they are quite responding to these new targeted therapies.
So there are some ongoing phase 3 clinical trials to evaluate this new compound in patients with androgen receptor ligand binding domain mutations with mCRPC disease that have failed prior systemic therapies. And we look for that data and the liquid NGS could help to detect these AR LBD mutations. And we can also check these mutations whether they had present in serial testing, because they may be happen not only in the first setting, they may develop in the subsequent setting when they have a progression of disease. So we can monitor these mutations to be happen in a serial measurement.
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Oncology Frontier- UroStream: Overall, what do you think is the most important implication of this liquid biopsy study targeting the Chinese population for advancing precision medicine in prostate cancer?
Dr. Darren M. Poon: Now for prostate cancer patients most of the time the metastasis will be happen in the bone. And you know with a bone biopsy it is challenging to provide sufficient tissue for the NGS, and a bone biopsy is invasive and painful. But for liquid NGS it is much more easier to provide sufficient DNA amount or content for the NGS analysis.
Secondly, most of the patients if they have a tissue biopsy that may be quite outdated, it may be happen during the first diagnosis for the prostate cancer from the prostate biopsy, but those tissue may not be in good quality and they are some archival tissues, and during the time of the tissue NGS retrieving those slides the quality of the tissue may be already affected and may not feasible to have the formal NGS. But for liquid NGS it implies that the quality of the tissue will not affect because
we just take a blood to monitor the liquid DNA. And it is much easier and also we can monitor the serial changes of the mutations with time.
So I think nowadays in Hong Kong we have more data on using liquid NGS in providing more informations about the genomic profiling for the metastatic prostate cancer patients. And we hope that by using liquid NGS it is easier and more convenient to the patients and the physician to provide a more personalized medicines approach.
Darren Poon
