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The 29th National Urology Conference (CUA2022), hosted by the Chinese Medical Association and the Urology Branch of the Chinese Medical Association (CUA), organized by the Shanghai Medical Association, and co-organized by Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine, was held
online on December 08-11, 2022 。 This year's annual meeting has set up 14 sub-venues such as tumor, stone, minimally invasive, urinary control, andrology, nursing, kidney transplantation, pediatric urology and laser, covering all aspects of the field of urology, comprehensively and deeply displaying and discussing the new progress and new technologies in the diagnosis and treatment of diseases in the industry, and will present a wonderful urology event
for everyone.
At the meeting, Professor Liu Zhuowei of the Cancer Center of Sun Yat-sen University shared with us the treatment strategies of high-risk NMIBC.
Professor Liu Zhuowei
Deputy Dean of Cancer Center of Sun Yat-sen University
Professor, chief physician, doctoral supervisor
China Urological Oncology Outstanding Youth Award
"Outstanding Young Medical Talents" and "Yangcheng Good Doctor" in Guangdong Province
Vice Chairman of the Multidisciplinary Diagnosis and Treatment Committee of Cancer of the Chinese Anti-Cancer Association
Member of the Clinical Research Committee of the Asian Society of Urological Robotics (ARUS).
Member of the Standing Committee of the CSCO Urothelial Carcinoma Committee
Member of the Standing Committee of the Urogenital Cancer Committee of the Chinese Anti-Cancer Association
Deputy leader of the Early Diagnosis and Early Treatment Collaborative Group of the Science Popularization Committee of the Chinese Anti-Cancer Association
Vice Chairman of Urology Branch of Guangdong Medical Association
Chairman-elect of the Genitourinary Oncology Professional Committee of Guangdong Anti-Cancer Association
Director of Guangdong Medical Doctor Association
Vice President of Guangdong Clinical Medical Association
Vice President of Guangdong Health Management Association
Domestic and foreign guidelines classify NMIBC into low-risk, intermediate-risk, high-risk or very high-risk groups, and the latest European guidelines also include risk factors
such as age, whether it is multiple, and tumor size.
At present, BCG bladder instillation is the preferred treatment
for high-risk NMIBC as consistently recommended by domestic and foreign guidelines.
However, BCG is less accessible, and there are BCG shortages even abroad; and BCG is a live bacterium preparation with specific adverse reactions (cystitis, hematuria, etc.
); What's more, BCG treatment failure is common, with studies reporting a 5-year recurrence rate of 66%
with BCG treatment.
Many drawbacks have brought certain challenges
to clinical work.
The Cancer Center of Sun Yat-sen University used arterial chemotherapy to replace the BCG regimen and achieved certain curative effects
.
Arterial chemotherapy is mainly used as gemcitabine + cisplatin (GC).
The advantage of arterial chemotherapy is that the drug concentration in local tissues is higher, and due to the low concentration of drug in circulating blood, systemic toxic side effects are small, and patients tolerate it well
.
From January 2000 to July 2015, Professor Liu Zhuowei's team treated 266 T1 patients (60 in the RC group, 63 in the GC group, and 143 in the conventional chemotherapy group), and all patients had positive events
within 1 year of follow-up or within 1 year.
Studies have shown that 83% of patients successfully conserve the bladder
after adjuvant arterial chemotherapy with GC regimens.
Compared with literature data from previous BCG perfusion therapy, adjuvant arterial chemotherapy with GC regimens is similar
in terms of tumor recurrence, progression, and disease-specific death.
The 3-year progression-free survival (PFS) and 3-year tumor-specific death (CSS) rates in this study were also comparable
to other literature data related to intravenous chemotherapy.
At the same time, arterial chemotherapy regimens have significantly less
hematologic toxicity than intravenous chemotherapy regimens.
Evaluation of the efficacy of arterial chemotherapy
Traditional molecular typing is not suitable for NMIBC, so Professor Liu Zhuowei's team has explored methods to evaluate the efficacy of arterial chemotherapy in clinical practice
.
The study found that stage T1 bladder cancer of the basal/squamous (BASQ) subtype benefited most significantly from arterial chemotherapy, while arterial chemotherapy did not significantly improve the efficacy
of patients with Luminal A subtype.
Subsequently, Professor Liu Zhuowei's team conducted a prospective study to compare the efficacy of T1 high-grade bladder cancer, arterial chemotherapy and BCG bladder instillation, with the primary endpoint of 2-year recurrence-free survival (RFS) and secondary endpoints of PFS, CSS, and bladder preservation rate
.
The results showed that the efficacy of arterial chemotherapy in GC regimen was comparable to that reported in retrospective studies.
The efficacy of domestic BCG bladder infusion is similar to that of international programs, and it is effective in preventing recurrence of T1 high-grade bladder cancer
.
At the same time, Professor Liu Zhuowei's team also evaluated
the efficacy of BCG bladder infusion therapy.
A total of 326 patients received BCG perfusion therapy, and a total of 311 patients completed follow-up
.
The results showed that the 1-year RFS rate was 82% and the 2-year RFS rate was 53%; The 1-year PFS rate was 96% and the 2-year PFS rate was 83%.
The efficacy of domestic BCG is similar
to that of foreign BCG.
At the same time, Professor Liu Zhuowei's team summarized the molecular characteristics of BCG perfusion benefits through whole exome/transcriptome sequencing, immunohistochemistry and other methods, and the immune infiltration of BCG ineffective group was more significant, and multiple immunosuppressive markers were highly expressed.
There were high-frequency mutations in STAG2 in the BCG effective group, and the DFS of the patients with the mutation showed a good trend (p=0.
075).
Treatment after BCG perfusion failure
PD-1 monoclonal antibody has been used in the second-line treatment of metastatic urothelial carcinoma and has achieved efficacy
.
In addition, for NMIBC patients with carcinoma in situ (CIS) who do not respond to BCG perfusion, the complete response (CR) rate of pembrolizumab monotherapy can reach 42% and be approved
by the FDA.
Radiation therapy is one of the conventional treatments for tumors, which can induce immunity and thus increase the effect of immunotherapy, so will radiation therapy and immune checkpoint inhibitors produce a 1+1>2 effect? Professor Liu Zhuowei's team carried out relevant research
.
The study selected suitable patients to receive tislelizumab plus radiotherapy, and the primary endpoint was a 1-year DFS rate
.
From August 2020 to August 2022, a total of 14 patients with bladder cancer were enrolled, with 8 courses of immunotherapy and a median radiotherapy dose of 60Gy/30F
.
The results showed a 1-year DFS rate of 80.
0% (95% CI 67.
4%-92.
6%) and a 2-year DFS rate of 60.
0% (95% CI 40.
3%-79.
7%)
.
The overall safety profile of this protocol was good, and 2 patients had grade 3 treatment-related adverse events, and no grade 4 or above adverse events
.
Finally, radical bladder cancer surgery is a well-known and guideline recommended treatment
for T1 grade NMIBC.
According to data from the Cancer Center of Sun Yat-sen University, the 5-year survival rate of patients with T1 high-grade NMIBC after radical surgery for bladder cancer reached 91%.
The Cancer Center of Sun Yat-sen University is establishing a T1G3 prognostic model based on CT image deep learning to better evaluate the prognosis
of NMIBC patients.
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