Professor He Zhisong, the new "cyst" Jing, talks about the advantages of adjuvant immunotherapy for urothelial carcinoma

*For medical professionals only, urothelial carcinoma (UC) is one of the common malignant tumors of the genitourinary system.
Among them, muscle-invasive bladder urothelial carcinoma (MIUC) has the characteristics of rapid progression, easy metastasis, high malignancy and Due to clinical characteristics such as poor prognosis, patients usually need to undergo radical cystectomy to save their lives, but about 50% of patients still experience postoperative recurrence [1], and the quality of life is worrying
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How to further reduce the incidence of postoperative recurrence and metastasis is one of the great challenges faced by the clinical diagnosis and treatment of urothelial carcinoma
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On April 23-24, the 2022 Chinese Society of Clinical Oncology (CSCO) Guidelines Conference will be held
.

Taking this opportunity, the medical community specially invited Professor He Zhisong, Chairman of the CSCO Urothelial Cancer Professional Committee and Peking University First Hospital Urology Department, to interpret and comment on the new progress of postoperative adjuvant therapy for urothelial cancer
.

Expert Profile Prof.
Zhisong He, Chief Physician, Department of Urology, Peking University First Hospital, Deputy Director, Institute of Urology, Peking University, Director, Department of Urology, Peking University First Hospital, Council Member, Chinese Society of Clinical Oncology (CSCO) Urinary Tract Chairman of the Skin Cancer Expert Committee Member of the Renal Cancer Professional Committee of the Chinese Society of Clinical Oncology (CSCO) Member of the Oncology Group of the Urology Branch of the Chinese Medical Association Member of the Urogenital Tumor Professional Committee of the China Anti-Cancer Association Member of the Urology Branch of Beijing Medical Association Member of the Chinese Medical Association Integrative Medicine Physician Branch of the Integrative Urology Professional Committee Director Guo Yinglu, member of the Anti-aging Professional Committee of China Aged Health Care Association, director of the Urology Development Foundation, Professor He Zhisong, chairman of the traditional adjuvant chemotherapy, said that the clinical needs of patients with muscle-invasive bladder urothelial carcinoma still face multiple clinical problems
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First, many patients are psychologically difficult to accept radical cystectomy; secondly, MIBC patients have a high risk of recurrence or metastasis after surgical treatment, and the long-term survival rate is not ideal.
The 5-year overall survival (OS) rate is about 50%-60%.
%[2]
.

The perioperative treatment of MIBC has been studied for more than 20 years.
Cisplatin-based chemotherapy is currently a commonly used adjuvant treatment for patients with high risk of recurrence after radical cystectomy, but this program is still controversial in clinical practice
.

Prof.
He Zhisong emphasized: "Traditional adjuvant therapy currently has major limitations.
Some patients cannot tolerate the toxicity of platinum-based chemotherapy, and the prognosis is relatively poor.
According to statistics, at least 40% of patients with urothelial carcinoma are not suitable for receiving cisplatin
.

" Some researchers It is pointed out that there is a lack of international consensus on adjuvant therapy for patients with poor pathology after cystectomy, and the needs of patients and clinicians have not been met
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Fortunately, this situation has changed with the publication of the results of the CheckMate-274 study
.

The Dawning CheckMate-274 study is the first and only confirmed immunotherapy for adjuvant therapy after radical resection of bladder or upper urinary tract urothelial carcinoma (UTUC), which can reduce the risk of disease recurrence in patients Phase III clinical study
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After many years of failed studies of immunotherapy as first-line or adjuvant therapy for UC, researchers are finally seeing a new light
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Professor He Zhisong pointed out that in the past, adjuvant therapy for UC has been lacking support from high-level large-scale clinical studies, because the adverse reactions of chemotherapy and surgical complications made it difficult to enroll patients, and the study was difficult to complete
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The CheckMate-274 study is the first global phase III clinical study with positive results, adding an important high-level evidence for adjuvant therapy in UC
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In terms of research endpoints, the data from the CheckMate-274 study showed that [3,4,5,6], regardless of PD-L1 expression, all populations achieved the "full load harvest" of the primary endpoint, secondary endpoints, and exploratory endpoints: Statistically significant extension of disease-free survival: doubling the increase Nivolumab doubled the median disease-free survival (DFS) of patients compared to the control group and reduced the risk of recurrence or death by 30%
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This benefit was more pronounced in patients with PD-L1 TPS ≥ 1%
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Note: NR, not reached (not reached); NE, not estimable (not evaluated) Not only that, according to the exploratory subgroup analysis data published by researchers at this year's American Society of Clinical Oncology Genitourinary Cancer Symposium (2022 ASCO-GU) [7], in patients with low PD-L1 expression, the DFS data of the nivolumab group also nearly doubled compared to the control group
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Prof.
Zhisong He commented: "The doubling of the DFS data means a definite delay in recurrence
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The results of the CheckMate-274 study are very surprising to us
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It also gives us a reassurance, allowing us to see the dawn of adjuvant immunotherapy after MIBC
.
"
More clinically meaningful improvement in NUTRFS: Controlling progression The CheckMate-274 study also showed that the median extraurethral recurrence-free survival (NUTRFS) was also nearly doubled in the nivolumab group compared with the control group, and tumor expression The benefit was more significant in patients with PD-L1≥1%
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Note: NR, not reached (not reached); NE, not estimable (not assessed) Prolonged DMFS of great exploratory value: early advantage Nivolumab can prolong the median distant metastasis-free survival (DMFS) of patients by more than 11 months, and the benefit was more significant in patients with tumors expressing PD-L1 ≥ 1%
.

Note: NR, not reached (not reached); NE, not estimable (not evaluated) "Currently, the overall survival (OS) data of the CheckMate-274 study has not been published, although OS prolongation is the 'ultimate goal' of tumor treatment, but specific to For each patient’s clinical treatment, doctors cannot accurately predict the patient’s OS, so the benefit of DFS or DMFS is also what we hope to see,” explained Prof.
He Zhisong, “This to some extent shows that drugs can delay the disease in patients.
The benefits brought by recurrence and progression
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"The future potential of adjuvant immunization recommended is unlimited.
The European Congress of Urology (EAU) guidelines and the National Comprehensive Cancer Network (NCCN) guidelines have successively recommended the use of nivolumab in urine.
Adjuvant therapy for epithelial carcinoma is recommended
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In 2021, based on the results of the CheckMate-274 study, the CSCO guidelines for the diagnosis and treatment of urothelial carcinoma officially list the use of nivolumab for postoperative adjuvant immunotherapy in MIUC and UTUC as a class II recommendation, and the level of evidence is the highest class 1A evidence.

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In this regard, Professor He Zhisong pointed out that when formulating guidelines, the guideline expert committee will not only consider evidence-based medical evidence, but also drug availability is one of the important factors
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Afterwards, Professor He Zhisong commented and looked forward to the challenges faced by the current UC clinical diagnosis and treatment: First of all, most domestic experts and scholars generally recognize the efficacy of postoperative adjuvant immunotherapy after MIUC, but there are still some problems with postoperative adjuvant therapy for UTUC.
controversy
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How UTUC patients can achieve better benefits through adjuvant immunotherapy remains to be explored in the future
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Second, the CheckMate-274 study showed breakthrough results for nivolumab monotherapy as adjuvant therapy after surgery
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However, whether adjuvant therapy such as immunotherapy combined with radiotherapy can bring greater benefits to patients is one of the directions for further exploration in the future
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Third, MIUC is known to be relatively more difficult to treat, so how to prevent the transformation of non-muscle-invasive urothelial carcinoma (NMIUC) to MIUC is crucial
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The results of the CheckMate-274 study reflect the application prospects of PD-1 inhibitors in the treatment of MIUC in the early stage.
In the future, in the process of advancing immunotherapy to the front-line treatment of MIUC, it is necessary to move forward step by step
.

References: [1] Stenzl A, Witjes JA, Cowan NC, et al.
Bladder Cancer Muscle-invasive and Metastatic.
2009.
[2] Jie Wu†, Rui-Yang Xie†, Chuan-Zhen Cao, et al.
Disease Management of Clinical Complete Responders to Neoadjuvant Chemotherapy of Muscle-Invasive Bladder Cancer: A Review of Literature.
Front.
Oncol.
, 13 April 2022.
[3] Bajorin DF, Witjes JA, Gschwend JE, et al.
Adjuvant Nivolumab Placebo in Muscle -Invasive Urothelial Carcinoma.
N Engl J Med.
2021;384:2102–2114.
2021.
[4] Opdivo [package insert].
New York, NY: Bristol Myers Squibb Company; 2021.
[5] Galsky MD, Witjes JA, Gschwend JE, et al.
Disease-free survvial with longer follow-up from the phase 3 CheckMate 274 trial of adjuvant nivolumab in patients who underwent surgery for high-risk muscle-invasive urothelial carcinoma,Poster presentation at the Society of Urologic Oncology (SUO) annual meeting.
December 1-3, 2021.
[6] Bajorin DF, Witjes JA, Gschwend JE, et al.
First results from the phase 3 CheckMate 274 trial of adjuvant nivolumab versus placebo in patients who underwent radical surgery for high-risk muscle-invasive urothelial carcinoma, Oral presentation at the 2021 Genitourinary Cancers Symposium (ASCO GU); February 11–13, 2021; Virtual Meeting.
[7] Matt D.
Galsky, Dean F.
Bajorin, J.
Alfred Witjes, et al.
Analysis of disease-free survival in CheckMate 274 by PD-L1 combined positive score and tumor proportion score.
2022 ASCO GU Poster 491.
*This article is for scientific information only for medical professionals, Does not represent the views of this platformFirst results from the phase 3 CheckMate 274 trial of adjuvant nivolumab versus placebo in patients who underwent radical surgery for high-risk muscle-invasive urothelial carcinoma, Oral presentation at the 2021 Genitourinary Cancers Symposium (ASCO GU); February 11–13, 2021; Virtual Meeting.
[7] Matt D.
Galsky, Dean F.
Bajorin, J.
Alfred Witjes, et al.
Analysis of disease-free survival in CheckMate 274 by PD-L1 combined positive score and tumor proportion score.
2022 ASCO GU Poster 491 .
*This article is only used to provide scientific information to medical professionals and does not represent the views of this platformFirst results from the phase 3 CheckMate 274 trial of adjuvant nivolumab versus placebo in patients who underwent radical surgery for high-risk muscle-invasive urothelial carcinoma, Oral presentation at the 2021 Genitourinary Cancers Symposium (ASCO GU); February 11–13, 2021; Virtual Meeting.
[7] Matt D.
Galsky, Dean F.
Bajorin, J.
Alfred Witjes, et al.
Analysis of disease-free survival in CheckMate 274 by PD-L1 combined positive score and tumor proportion score.
2022 ASCO GU Poster 491 .
*This article is only used to provide scientific information to medical professionals and does not represent the views of this platformAnalysis of disease-free survival in CheckMate 274 by PD-L1 combined positive score and tumor proportion score.
2022 ASCO GU Poster 491.
*This article is only for providing scientific information to medical professionals and does not represent the views of this platformAnalysis of disease-free survival in CheckMate 274 by PD-L1 combined positive score and tumor proportion score.
2022 ASCO GU Poster 491.
*This article is only for providing scientific information to medical professionals and does not represent the views of this platform