Editor’s Note: Urothelial carcinoma (UC) is one of the most common malignancies of the urinary system. For early-stage non–muscle-invasive disease, treatment typically involves transurethral resection of bladder tumor (TURBt) followed by intravesical therapy, while postoperative monitoring primarily relies on cystoscopy and urine cytology. At the 2025 ASCO Annual Meeting, Professor Zhisong He from Peking University First Hospital shared the latest research progress in UC, including prospective studies on novel intravesical agents and urine-based liquid biopsy for minimal residual disease (MRD) detection led or co-led by his team.Oncology Frontier – UroStream: What do you consider to be the most important recent innovations in UC research in China, particularly in the field of antibody–drug conjugates (ADCs)?
Professor Zhisong He: With recent breakthroughs in ADC therapies internationally, the landscape of UC treatment has undergone profound change. These advances have led to updates in treatment guidelines and major shifts in frontline therapy strategies, all of which have had significant clinical implications. Chinese researchers have played an important role in these developments. Notably, Professor Jun Guo and his team from Peking University Cancer Hospital were among the first globally to demonstrate the efficacy of the HER2-targeting ADC RC48 in patients with HER2-positive UC. Findings from this and related clinical trials have been presented at major conferences such as ASCO and ASCO-GU and published in top-tier oncology journals. This year, we eagerly await the results of a randomized phase III trial evaluating RC48 in combination with immunotherapy as first-line treatment for advanced UC. These efforts underscore the substantial contributions made by Chinese investigators in the UC field.
Of course, the UC field is complex and includes subtypes such as upper tract urothelial carcinoma (UTUC)—including renal pelvis and ureter cancers—and lower tract UC, such as bladder and urethral cancers. These subtypes differ in biological behavior and prognosis. Within bladder cancer specifically, we distinguish between non–muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). In the relatively early-stage NMIBC setting, Chinese researchers have also made notable progress. Some of these advances are based on cutting-edge global therapies, but others reflect domestic innovation. For example, at this year’s ASCO meeting, two novel intravesical agents—BH011 and SHR-1501—were presented. We are hopeful that the results of these studies will soon translate into improved clinical practice.
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Oncology Frontier – UroStream: Could you tell us more about the preliminary results of the novel intravesical therapies BH011 and SHR-1501?
Professor Zhisong He: Both studies are still in progress and have not yet released final data. Peking University First Hospital is one of the participating centers. Based on the interim findings so far, the results are promising and meet our expectations, which supports the continuation of both research programs.
BH011 is a novel docetaxel-based intravesical formulation designed to improve drug concentration and tissue penetration. In our phase 1/2 study involving patients with high-risk NMIBC who had failed BCG therapy, the complete response rates (CRR) at 3 months and 1 year were 96% and 71%, respectively. The median recurrence-free survival (RFS) reached 20.21 months, and the treatment was well tolerated. Only grade 1–2 adverse events were observed—primarily urinary tract infections and hematuria—and no treatment discontinuations occurred.
SHR-1501, on the other hand, is a novel IL-15 receptor agonist fusion protein that enhances the activity of natural killer (NK) cells and CD8+ T cells. In our phase 1/2 study, SHR-1501, either alone or in combination with BCG, showed encouraging preliminary efficacy. In Cohort B (patients with CIS who were unresponsive to BCG), the complete response rate at 3 or 6 months was 90.9%. In Cohort A (BCG-naïve patients) and Cohort C (papillary tumors unresponsive to BCG), the 9-month disease-free survival (DFS) rates were 94.4% and 53.9%, respectively. There were no dose-limiting toxicities (DLTs), and the maximum tolerated dose (MTD) was not reached.
Both trials are ongoing. We know that many clinical trials are terminated prematurely when interim results fall short of expectations, and development plans are often withdrawn. However, BH011 and SHR-1501 continue to show promising outcomes, and their trials are progressing smoothly. We are optimistic that these two innovative therapies will ultimately deliver positive results and offer more effective treatment options for patients with high-risk NMIBC.
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Oncology Frontier – UroStream: At this year’s ASCO meeting, your center presented a new study that has begun enrolling patients for MRD monitoring using urine DNA. Could you tell us more about this research?
Professor Zhisong He: In the field of urothelial carcinoma, one of the persistent challenges is how to achieve early diagnosis and, after treatment, how to evaluate therapeutic response and detect early recurrence. These are ongoing clinical pain points. Fortunately, many Chinese researchers have already made impressive progress in urine-based diagnostics. This includes methylation detection, as well as our team’s study presented at this year’s meeting on urine DNA–based MRD (minimal residual disease) monitoring.
This research involves sequencing DNA from patient urine samples—including urinary cell-free DNA (ucfDNA) and urinary exfoliated DNA (uexDNA)—to calculate an MRD score, which is then compared with current “gold standard” methods such as cystoscopy ± biopsy and imaging (CT/MRI). The study plans to enroll 400 urothelial carcinoma patients, divided into four cohorts:
- Cohort 1: Postoperative high-risk UTUC patients (pT3-4 or N+);
- Cohort 2: NMIBC patients after TURBt;
- Cohort 3: MIBC patients scheduled for neoadjuvant therapy;
- Cohort 4: Patients achieving complete response (CR) following standard trimodal bladder-preserving therapy (TMT).
In our earlier work, this non-invasive urine-based diagnostic approach demonstrated encouraging sensitivity and specificity in both early UC screening and MRD detection. We look forward to validating these results further through this multicenter prospective observational study, and we hope this technology can make a meaningful impact on early diagnosis and treatment monitoring in urothelial carcinoma.
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Oncology Frontier – UroStream: Looking ahead, what emerging technologies do you believe could be applied in cancer diagnosis and treatment—particularly given the strong presence of artificial intelligence (AI) at this year’s ASCO?
Professor Zhisong He: As artificial intelligence (AI) continues to enter the clinical space, its role in diagnosis is becoming increasingly indispensable, and the transformations it could bring are beyond what we can currently predict. That said, keeping pace with this technological trend—and not being left behind—is something every clinician must take seriously.
At this year’s ASCO Annual Meeting, a dedicated session was held titled “AI, Improving Cancer Care, and the Future of Collaboration.” One of the key questions being discussed was whether AI might eventually replace doctors. Experts highlighted an extremely important point: AI will not replace physicians—but physicians who can use AI will outperform those who cannot.
I believe this is a message we must embrace. We should fully harness this cutting-edge technology and apply it in areas most in need of improvement—particularly in the realm of human health, so we can achieve breakthroughs and make meaningful contributions to the well-being of people around the world.
