Welcome to “PI Perspectives,” a brand-new series under the “Ruiyun Talks” platform.
The purpose behind launching this series is very clear: more and more original, high-quality clinical studies are emerging from China, and we hope to amplify their voices—not only domestically, but also internationally through our platform for global academic exchange and communication.In each episode, we invite leading principal investigators (PIs) in the field of uro-oncology in China to share firsthand insights into their own landmark clinical research and the thinking behind it.
For the very first episode of Season 1, we are honored to welcome two academic leaders from West China Hospital’s “Bladder Preservation Team” — Professor Zhang Peng and Professor Shen Yali — to jointly interpret the HOPE study series.
Why Did We Choose the HOPE Series for the Premiere Episode?
There are three major reasons why the HOPE series was selected as the opening feature of “PI Perspectives.”
First: Its Systematic Nature
The HOPE series represents the most systematic prospective bladder-preservation research program in Chinese uro-oncology to date.
From its debut at ASCO 2021 through HOPE-01 to HOPE-04, the program has evolved through four generations of studies, covering the full technological evolution of bladder preservation strategies—from real-world exploration, chemo-immunotherapy combinations, ADC plus immunotherapy regimens, to ultra-hypofractionated radiotherapy.
This kind of “multi-generation, forward-progressing” research framework deserves in-depth discussion.
Second: Long-Term Follow-Up
HOPE-02 has now reached a median follow-up of four years, making it the longest follow-up study among comparable bladder-preservation trials worldwide.
A sufficiently long follow-up period means the data no longer remain at the level of “preliminary results,” but instead enter the ultimate proving ground of bladder-preservation research: long-term survival and functional preservation.
Third: Courage
HOPE-02 enrolled patients with cT4b disease, node-positive disease, and even M1a metastasis—an inclusion criterion that is arguably the boldest among all global bladder-preservation studies.
This means the HOPE series stepped beyond the traditional “comfort zone” of bladder preservation, and this willingness to explore controversial patient populations is exactly the kind of courage that Chinese original research needs to be recognized and discussed globally.
We believe that through direct discussions with the two principal investigators, more clinicians worldwide will better understand the clinical logic and research philosophy behind the HOPE series, while also strengthening China’s voice in the global bladder-preservation landscape.
The West China “Bladder Preservation Team”:
A Dual-Engine Model of Surgery and Radiation Oncology
The West China Hospital “Bladder Preservation Team” is jointly led by Professor Zhang Peng from Urology and Professor Shen Yali from Abdominal Oncology/Radiation Oncology.
What makes this team unique is that it was never designed as a surgery-driven program alone. From the very beginning, it was built as an MDT system powered by a dual-PI structure combining surgery and radiation oncology.
Professor Zhang Peng (Department of Urology)
Responsible for:
- Patient selection
- TURBT surgical quality control
- Neoadjuvant treatment decisions
- Salvage radical cystectomy after bladder-preservation failure
His role defines the “safety boundary” of bladder preservation:
when can the bladder safely be preserved, and when must cystectomy be performed?
Professor Shen Yali (Department of Abdominal Oncology/Radiation Oncology)
Responsible for:
- Radiotherapy planning
- Integration of radiotherapy with systemic treatment sequencing
- Management of radiotherapy-related adverse events
Her role defines the “technical ceiling” of bladder preservation:
how to delineate radiation targets, determine dosing strategies, and coordinate radiotherapy with immunotherapy and ADCs.
It is precisely this dual-engine structure—“surgery defining the boundaries, radiotherapy defining the upper limit”—that enables the West China team to challenge broader inclusion criteria than traditional trimodality therapy (TMT).
They are not viewing bladder preservation through the lens of a single specialty, but rather through a comprehensive MDT management system that supports every clinical decision related to expanding indications.
Another important byproduct of this collaborative model is that the HOPE series naturally developed a translational closed-loop structure driven by “surgical needs” and “radiotherapy implementation.”
From HOPE-01 to HOPE-04, every generational upgrade has represented not merely a drug substitution, but a bidirectional evolution between clinical surgical demands and advances in radiotherapy technology.
Expert Quotes
Professor Zhang Peng
“HOPE represents both the ‘H’ of Huaxi (West China) and the ‘H’ of hope itself. We hope bladder preservation can become a source of hope for more patients.”
Professor Shen Yali
“Bladder cancer is a disease that truly reflects multidisciplinary collaboration and full-process team management.”
Professor Zhang Ruiyun
“Bladder preservation is not a shortcut. It requires genuine integration between surgery, radiation oncology, and medical oncology, along with a far more sophisticated full-course management system than radical cystectomy alone.”
I. Bladder Preservation:
From the TMT Era to a New Era
Bladder-preservation therapy for muscle-invasive bladder cancer (MIBC) is not a new concept.
Traditional trimodality therapy (TMT)—consisting of TURBT plus chemotherapy and radiotherapy—has accumulated decades of follow-up data from institutions such as Massachusetts General Hospital, demonstrating that in carefully selected patients, long-term survival outcomes are not inferior to radical cystectomy (RC).
However, the TMT era had a fundamental limitation:
the definition of “ideal bladder-preservation candidates” was extremely strict.
Patients generally had to meet criteria such as:
- T2 disease only
- No carcinoma in situ
- No hydronephrosis
- Node-negative disease
Once patients exceeded these boundaries, guidelines typically recommended radical cystectomy.
In 2018, immunotherapy was approved by the FDA for urothelial carcinoma, ushering bladder cancer treatment into a new era of systemic therapy.
Subsequently, the emergence of antibody-drug conjugates (ADCs) further expanded the therapeutic arsenal.
This raised a fundamental question:
In an era where systemic therapy has dramatically improved, can the boundaries of bladder preservation also be expanded?
The HOPE series from the West China Hospital “Bladder Preservation Team” represents a systematic answer to this question.
II. HOPE:
The Philosophy Behind the Name
The name “HOPE” was personally created by Professor Zhang Peng.
As he recalled during the interview:
“Because we represent West China Urology, and ‘Huaxi’ starts with the letter H. The best word beginning with H was ‘HOPE.’ We hope bladder preservation can become a hope for more patients—allowing them to control their disease while preserving quality of life. That is the shared hope of both doctors and patients.”
HOPE therefore represents both:
- the “H” of Huaxi (West China)
- and the “H” of hope itself.
From the very beginning, the name embodied the team’s core philosophy:
preserve the organ, preserve quality of life, and preserve hope—without compromising oncologic control.
III. Evolution of the HOPE Series:
From Real-World Exploration to Prospective Breakthroughs
Since its first ASCO presentation in 2021, the HOPE series has evolved through four generations of studies, each precisely aligned with key turning points in bladder cancer treatment.
HOPE-01:
Real-World Exploration (ASCO 2021)
When immunotherapy first entered the urothelial carcinoma field, expectations were extremely high.
HOPE-01 was a retrospective real-world study comparing:
- chemotherapy plus immunotherapy (tislelizumab)
versus - chemotherapy alone
in locally advanced MIBC.
The findings were thought-provoking.
In the chemotherapy-alone group:
- not a single patient achieved clinical complete response (cCR).
In contrast, in the chemo-immunotherapy group:
- the cCR rate reached 50%,
even among patients with T3–T4 disease and node-positive disease.
Professor Zhang Peng recalled:
“Many patients in western China present at a very advanced stage at diagnosis. In the chemotherapy-alone group, no patient achieved cCR. But after adding immunotherapy, the cCR rate reached 50%.”
This 50% cCR rate became the foundation for all subsequent studies.
If chemo-immunotherapy could induce cCR in nearly half of locally advanced patients, could some of these patients avoid cystectomy altogether?
HOPE-02:
Chemo-Immunotherapy Plus Radiotherapy for Bladder Preservation
HOPE-02 administered four cycles of chemo-immunotherapy, followed by sequential radiotherapy for patients without progressive disease (PD), aiming to preserve the bladder.
The inclusion criteria were exceptionally bold:
- cT2–4b
- N0–3
- M0–1a
This represented one of the highest-risk populations ever included in a bladder-preservation trial worldwide.
Currently, HOPE-02 has achieved a median follow-up of four years, the longest among comparable studies.
Key findings include:
- cCR rate after neoadjuvant chemo-immunotherapy: 51.1%
- Overall cCR rate after sequential radiotherapy: 100%
- 3-year bladder-intact disease-free survival: 76%
- 3-year overall survival: 81%
The study is currently under submission for publication.
HOPE-03:
First Bladder-Preservation Attempt Replacing Chemotherapy with ADC Therapy
With ADCs entering clinical practice, HOPE-03 replaced chemotherapy with:
- disitamab vedotin (RC48, a HER2-targeting ADC)
combined with - tislelizumab
followed by sequential radiotherapy for bladder preservation.
At EAU 2026, HOPE-03 was presented as a featured conference presentation with updated data:
- cCR rate after neoadjuvant ADC-immunotherapy: 64.4%
- 2-year overall survival: 89.4%
Median follow-up is now approaching three years.
HOPE-04:
Ultra-Hypofractionated Radiotherapy Plus Immunotherapy in NMIBC
While the first three studies focused on MIBC, HOPE-04 shifted attention toward:
- high-risk non-muscle-invasive bladder cancer (NMIBC)
- especially BCG-unresponsive and recurrent disease.
The study uses an innovative regimen of:
- 5 × 5 Gy ultra-hypofractionated radiotherapy
combined with - immunotherapy
to explore the synergistic effects between radiation and immune activation.
Core Topics of “PI Perspectives” Season 1
In the next five episodes, together with Professors Zhang Peng and Shen Yali, we will further explore the following major topics surrounding the HOPE series:
- Why did HOPE-02/03 dare to enroll patients with cT4b, node-positive disease, and even M1a metastasis?
- What clinical logic and radiotherapy strategies supported this expansion of eligibility criteria?
- Compared with studies such as NIAGARA, RETAIN-2, and INDIBLADE, what distinct clinical messages does HOPE-02 deliver?
- In the chemo-immunotherapy era, which direction should bladder preservation take?
- Behind the remarkable HOPE-03 results, how large is the gap between cCR and pCR?
- Can restaging TURBT bridge that gap?
- How has the role of radiotherapy evolved within the HOPE series—from consolidation therapy to definitive treatment and innovative ultra-hypofractionated designs?
- What is the MDT collaboration mechanism behind the West China “Bladder Preservation Team”?
- And what lies ahead in the future roadmap of HOPE-07, HOPE-08, and HOPE-09?
Professor Zhang Ruiyun
