With diagnostic and therapeutic technologies advancing rapidly, precision treatment strategies for genitourinary malignancies such as urothelial carcinoma and prostate cancer are evolving with growing momentum. At the recent 2025 Annual Meeting of the European Association of Urology (EAU25), Professor Jeremy Teoh of The Chinese University of Hong Kong and Professor Yige Bao of West China Hospital, Sichuan University both presented major findings or received distinguished honors, showcasing the academic strength and international influence of Chinese urologists.  UroStream invited both experts for an insightful conversation on their research, clinical progress, and evolving strategies in the treatment of urothelial and prostate cancers.

UroStream: First, I’d like to invite both of you to kick off this dialogue with your research findings or interests.Professor Bao, we know your study (abstract A0059) on kidney – sparing treatment with ADC and immunotherapy in UTUC patients was accepted at this EAU conference. Could you share the results?

Prof. Yige Bao: Sure, we’re very happy and honored to share some of our data about kidney-sparing treatment for UTUC patients. According to current EAU guidelines, only low-risk UTUC patients are eligible for kidney-sparing treatments. However, in real-world practice, we frequently encounter patients who have only one functional kidney, bilateral tumors, or severe chronic kidney disease—situations where radical nephroureterectomy could lead to dialysis.

To address this, we conducted two clinical trials integrating local and systemic therapies for high-risk patients. One trial involved the HER2-targeted antibody-drug conjugate RC48 (disitamab vedotin) combined with a PD-1 immune checkpoint inhibitor and endoscopic laser ablation. This was applied in a selected cohort of 31 localized high-risk UTUC patients who were HER2-positive.

With a median follow-up of 24 months, the one-year conversion-free survival rate was 91.2%, and the two-year rate was 88.9%. These promising results demonstrate that, with systemic treatment support, most patients were able to preserve their kidneys.

This approach offers an important alternative for patients with a solitary kidney or bilateral disease and shows that, even in high-risk UTUC, kidney preservation is achievable in selected cases.

UroStream: Professor Teoh, your CUHK has many studies here. You have been awarded the 2025 EAU Best Paper on Clinical Research which is a randomized trial of transurethral en bloc resection of the bladder for NMIBC. Could you share this study with us?

Prof. Jeremy Teoh: In this study involving patients with non–muscle-invasive bladder cancer, we enrolled 350 participants who were randomized to receive either en bloc resection—removal of the tumor in one piece—or conventional piecemeal resection. Traditionally, resections were done in a top-down, fragmented manner. En bloc resection aims to reduce tumor cell spillage, lower the risk of implantation, and ensure a complete tumor removal by enabling clear margin evaluation.

We found that en bloc resection significantly reduced the one-year recurrence rate—from 38.1% to 28.5%. Moreover, for patients with low-risk, solitary tumors, surgery alone proved highly beneficial. In high-risk patients, surgery is only part of the equation. While a high-quality resection minimizes residual disease, tumor biology—including high grade, multifocality, or carcinoma in situ—must also be addressed.

Among high-risk patients, those receiving en bloc resection plus BCG therapy achieved a one-year recurrence rate of approximately 5% and two-year rate around 10%.As urologists, we believe that performing a high-quality surgery is the foundational step. And in high-risk cases, combining surgery with effective adjuvant therapy can potentially cure many patients. We’re truly honored to receive the EAU Best Paper award. This reflects the collaborative efforts of all participating centers in Hong Kong. I also look forward to working with Professor Bao on future UTUC trials—we have great potential to make meaningful international contributions.

Prof. Yige Bao: Yes, and I want to add that this prize holds great significance—not only for Dr. Teoh, but for all Chinese urologists. At the EAU conference, there was a display board listing all awarded papers, and Dr. Teoh’s study was prominently placed right in the center. The moment I saw it, I took a photo—it was my favorite snapshot of the entire day.

Conducting randomized controlled trials in surgery, especially with positive outcomes, is never easy. Consider previous technique trials—like monopolar vs. bipolar TURP or open vs. robotic surgery—very few surgical RCTs yield strong results. One major challenge is the variability in surgical techniques among different surgeons.In this study, 13 hospitals in Hong Kong participated, each with varying patient volumes, expertise levels, and surgical experience. So how did you ensure consistency and quality control across so many centers?

Prof. Jeremy Teoh: It all comes down to the design and execution quality of the randomized trial. First, we made sure all participating surgeons were well-trained in the en bloc technique. Next, the entire protocol—surgical, postoperative management, and follow-up—was standardized across all centers.Bladder cancer is highly heterogeneous. If we change one treatment component without controlling the rest of the management pathway, the effect gets diluted, possibly resulting in a negative outcome. So yes, ensuring protocol adherence and quality checks at every step is vital.I truly believe that with the patient volume and clinical talent in China, we’re well-positioned to run more high-quality trials. I look forward to collaborating with more centers in the future to design impactful studies that influence global practice.

Prof. Yige Bao: I really appreciated this paper. After I read it, I immediately recommended it to everyone in our department. Now it’s well known among all our colleagues. Before this, when we discussed en bloc resection, we said it was a promising technique but lacked solid evidence.

Now, that has changed. We have robust, high-quality data. This study will surely be cited in upcoming guidelines. And future generations learning en bloc resection will learn it through this paper.So once again, congratulations. It’s a remarkable study. Thank you for conducting it.

UroStream: Both of you mentioned organ – sparing treatments (e.g., bladder – sparing, kidney – sparing). Recently, ctDNA liquid biopsies have been used to follow – up such patients, like in the TOMBOLA study presented at this EAU conference. What are your views on the ctDNA applications in urological tumors?

Prof. Jeremy Teoh: So I think without a doubt, organ-sparing approaches, or bladder-sparing treatments, are going to be the future. The key challenge is how we plan an effective clinical pathway: selecting the right patients, offering the right treatment, and following up accordingly. In the past, this was difficult due to the lack of robust selection tools. Now, we use more imaging, like MRI scans—not only preoperatively but also postoperatively—to assess whether disease remains in the bladder.

Previously, when performing conventional resections, especially for large tumors, many surgeons used to perform a so-called staging TURBT where gross residual disease would remain at the base. If we want to truly adopt bladder-sparing treatments, we need a good, maximal resection from the start. Even in en bloc resections, we apply modified approaches to ensure maximum resection.

We’re still developing ways to predict systemic treatment response. For example, in the PURE-01 study, some biomarkers appeared to predict response to pembrolizumab. Though the evidence is still limited, imagine you have a large tumor that has been well resected. The tissue from that resection could be tested for biomarkers to predict which systemic therapies will be effective.

Finally, what you’ve mentioned—ctDNA—is especially promising. Let’s say we give one or two years of treatment, then use ctDNA for follow-up. If ctDNA remains negative, perhaps we can safely stop treatment. If ctDNA changes from negative to positive, indicating minimal residual disease, we may need to restart therapy. While the entire treatment pathway hasn’t yet been fully defined, we now have most of the essential components to build a robust bladder-sparing strategy. We’re in a good position to design meaningful studies.

Prof. Yige Bao: Yeah, I strongly agree with Dr. Teoh. The use of ctDNA and related approaches like utDNA is certainly one of the future directions we will be working on. The challenge now is that, while sequencing and molecular analysis technologies are evolving rapidly, the statistical tools required to handle and interpret the data are still lagging behind. We have an abundance of sequencing data, but we lack ideal statistical methods for interpreting them effectively. Sequencing data is compositional—it exists in a closed, Euclidean space—unlike traditional open-space data. As a result, applying standard statistical methods may lead to a high risk of false-positive results. So while we already recognize ctDNA and utDNA as promising tools for the future, we still need more robust data, refined techniques, and specialized statistical methodologies to fully determine their optimal clinical application.

Prof. Jeremy Teoh: What you said is very thought-provoking. Researchers have used RNA sequencing to classify bladder cancer subtypes, but this classification often has limited clinical relevance—especially in determining which treatment to give—because these subtypes are not based on actual treatment response.

To overcome this, we need long-term, response-based data. If we had a cohort of bladder or UTUC patients with sequencing data, and we administered treatments like chemotherapy or immunotherapy, and tracked responses, we could then identify molecular signatures that guide treatment selection. Globally, we lack this kind of real-world treatment-response data, and it’s something the field urgently needs.

Prof. Yige Bao: Yes, developing statistical models is the job of statisticians, but it’s our job as urologists to conduct more clinical trials and generate relevant datasets—especially data that reflects Chinese patient populations. We hope Dr. Teoh will lead more China-initiated urology trials so we can collectively contribute data and move this field forward together.

UroStream: In prostate cancer, PARP inhibitors have revolutionized mCRPC treatment by enabling precision therapy for HRRm patients. Can ctDNA HRRm detection replace tissue testing? As we know that PROpel study showed over 85% consistency between ctDNA and tissue testing, What’s your take on this?

Prof. Yige Bao: Thanks. Well, from my personal point of view, ctDNA is a great option—an excellent alternative for DNA testing. Often, the decision to perform DNA sequencing is made when a patient enters the mCRPC phase. By then, the patient has usually been receiving systemic therapy for about three to five years, during the mHSPC stage. Looking back at their original biopsy samples, the tissue is often degraded, and its quality may be suboptimal for DNA analysis.

Sometimes we attempt a re-biopsy, but the prostate may not yield a representative or positive sample, especially after prolonged systemic therapy. Targeting metastatic lesions can also be challenging—particularly when they involve bone or deep lymph nodes in areas like the perineal region.

At that point, ctDNA—or what we call liquid biopsy—offers a very convenient alternative. It only requires a blood sample. Current data suggests that ctDNA provides highly representative results, comparable to tissue biopsy. One caveat, however, is that ctDNA may occasionally miss certain DNA repair mutations, especially the homologous BRCA2 deletions (BRCA2-Holmdel), where both BRCA2 alleles are entirely deleted. These patients tend to respond best to PARP inhibitors, but such deletions might go undetected by ctDNA testing. Still, this is a rare exception. In most cases, ctDNA is a highly valuable tool for gene testing.

Prof. Jeremy Teoh: In the context of metastatic disease, tumor burden is generally higher, and we can often detect circulating tumor cells (CTCs). That’s also why, in the PROpel study, most patients were CTC-positive at the time of screening.Blood-based tests are much more convenient than going back to archived biopsy samples or attempting re-biopsies, which are often technically difficult. I fully agree—ctDNA is a promising option. However, in very specific cases, particularly when ctDNA results are inconclusive or when histological confirmation is required, a tissue biopsy remains a valid approach.

In our region, especially at the mCRPC stage when treatment options start narrowing, gene testing becomes increasingly relevant. We also consider genetic testing in patients with strong family histories of prostate cancer, or in young patients, where HRR mutations may be more likely. In such cases, precision therapy with PARP inhibitors is worth considering.

UroStream: Both ctDNA and tissue testing aim to ensure mCRPC patients get effective PARPi treatment, as proven beneficial in PROpel and other studies.When and how do you conduct gene testing in clinical practice? Also, share your experience in managing PARPi monotherapy and combination therapy.

Prof. Jeremy Teoh: As mentioned, especially in advanced cases, we tend to test for mutations in younger patients—typically under 60—or in those with atypical histology, like ductal-type prostate cancer, or a strong family history involving first-degree relatives. Based on those findings, we proceed with precision therapy. PARP inhibitors—either as monotherapy or in combination—are quite well tolerated and easy to manage in terms of side effect profiles. In Hong Kong, this approach is increasingly accepted and implemented.

Prof. Yige Bao: I strongly agree with Dr. Teoh. In clinical practice, DNA testing is most commonly discussed when the patient transitions into the mCRPC phase. However, in certain situations, we even discuss early testing at diagnosis, especially for younger patients or those with clear family histories.We’re also running a clinical study examining the rate of DNA mutations in patients showing poor PSA response after six years of HSPC treatment. These cases are more likely to harbor actionable mutations.To address the issue of suboptimal sample quality, one solution we’re working on involves early DNA extraction. At the time of initial diagnosis, when patients undergo systemic biopsy, they can opt to have DNA extracted and stored. This is a low-cost process, and the DNA can be frozen and used later if the patient progresses to mCRPC. That way, we avoid challenges in acquiring viable tissue at later stages.

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References

[1] Ye J, et al. Kidney-sparing approach for selected localized high-risk upper tract urothelial carcinoma: A pilot study combining endoscopic Thulium laser ablation with perioperative Disitamab vedotin and immune checkpoint inhibitors. Presented at EAU25. Abstract A0059.

[2] Teoh Yuen-Chun J, Cheng CH, Tsang CF, et al. Transurethral En Bloc Resection Versus Standard Resection of Bladder Tumour: A Randomised, Multicentre, Phase 3 Trial. Eur Urol. 2024;86(2):103–111. doi:10.1016/j.eururo.2024.04.015

[3] Reike MJ, Raggi D, Mercinelli C, et al. Distinct Gene Expression Patterns Identify Patients Who Relapse After Neoadjuvant Pembrolizumab and Radical Cystectomy in the PURE-01 Study. Clin Genitourin Cancer. 2024;22(6):102214. doi:10.1016/j.clgc.2024.102214

[4] Armstrong AJ, et al. Detection of Mutations in Homologous Recombination Repair Genes in Tumour Tissue and Circulating Tumour DNA from Patients with Metastatic Castration-Resistant Prostate Cancer in the Phase II PROpel Trial. Presented at ESMO 2022. Abstract 2690.

Professor Jeremy Teoh

The Chinese University of Hong Kong

• Assistant Dean (External Affairs), Faculty of Medicine, The Chinese University of Hong Kong
• Associate Professor, Division of Urology, CUHK
• Director, Urology Centre, CUHK Medical Centre
• Director, Robotic Surgery Services, CUHK Medical Centre
• Visiting Professor, Medical University of Vienna
• Member, Non-Muscle-Invasive Bladder Cancer (NMIBC) Guidelines Panel, European Association of Urology (EAU)
• Member, Communications Committee, EAU Guidelines Office
• Consulting Editor, European Urology
• Associate Editor, European Urology Oncology
• Member, EAU Young Urologists Office – Urothelial Cancer Working Group
• Chair, Congress Organizing Committee, Société Internationale d’Urologie (SIU)
• Member, SIU Innovators Program
• Recipient, 2021 SIU Innovators Award
• Awardee, 2021 Ten Outstanding Young Persons of Hong Kong
• Author of over 400 peer-reviewed publications
• Recipient of over HKD 80 million in competitive research funding

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Professor Yige Bao

West China Hospital, Sichuan University

• MD, PhD, Associate Professor
• Director, Department of Urology, Ganzi Hospital, West China Hospital, Sichuan University
• Vice Chair, Youth Committee of the Urology Branch, Chinese Medical Doctor Association
• Member, Youth Committee, Urology Branch, Chinese Research Hospital Association
• Vice Chair, Youth Committee, Urology Branch, Sichuan Medical Doctor Association
• Member, Youth Committee, Sichuan Society of Reproductive Medicine
• Published over ten research articles in national and international journals
• Co-author of one academic monograph
• Principal investigator of one National Natural Science Foundation of China (NSFC) Young Scientists Fund project
• Contributor to the drafting of a national expert consensus guideline