Xiaotong Huang, Xuan Wang, Zihe He, Yishu Huang, Bing Hu, Weiying Chen, Haifang Du
{"title":"非肌肉浸润性膀胱癌中bcg无反应的机制、临床试验和新治疗方法","authors":"Xiaotong Huang, Xuan Wang, Zihe He, Yishu Huang, Bing Hu, Weiying Chen, Haifang Du","doi":"10.1002/cam4.71243","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Bacillus Calmette–Guérin (BCG) is the standard adjuvant therapy for high-risk non-muscle invasive bladder cancer (NMIBC), yet treatment failure occurs in 30% to 40% of patients. Those with BCG-unresponsive disease face a high risk of progression and represent a critical unmet need in urologic oncology. This review summarizes the mechanisms of BCG failure and evaluates emerging therapies for BCG-unresponsive NMIBC.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We conducted a comprehensive literature review of clinical trials and preclinical studies through August 2025, focusing on therapeutic strategies for BCG-unresponsive NMIBC. Mechanisms of BCG resistance, regulatory definitions, and results from recent Phase II/III trials were analyzed.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Multiple novel therapies have demonstrated efficacy in BCG-unresponsive patients. Immune checkpoint inhibitors (e.g., pembrolizumab) achieved complete response (CR) rates of 41% in carcinoma in situ (CIS) patients. Gene therapies such as nadofaragene firadenovec and CG0070 induced CR rates of 51% and 75%, respectively. Device-assisted therapies including hyperthermic intravesical chemotherapy (HIVEC) showed 24-month recurrence-free survival of 57.4%. The IL-15 superagonist Anktiva (nogapendekin alfa inbakicept), recently FDA-approved, achieved a 71% CR rate with a median duration of 26.6 months when combined with BCG.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>The treatment landscape for BCG-unresponsive NMIBC is rapidly evolving, with immune checkpoint inhibitors, gene therapies, targeted agents, and advanced drug delivery systems showing promising efficacy. These innovations provide bladder-preserving options for patients ineligible for radical cystectomy. Future directions include biomarker-driven therapy selection, combination regimens, and optimized intravesical delivery platforms to improve long-term outcomes.</p>\n </section>\n </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 18","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71243","citationCount":"0","resultStr":"{\"title\":\"Mechanisms, Clinical Trials, and New Treatments for BCG-Unresponsive in Nonmuscle Invasive Bladder Cancer\",\"authors\":\"Xiaotong Huang, Xuan Wang, Zihe He, Yishu Huang, Bing Hu, Weiying Chen, Haifang Du\",\"doi\":\"10.1002/cam4.71243\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Bacillus Calmette–Guérin (BCG) is the standard adjuvant therapy for high-risk non-muscle invasive bladder cancer (NMIBC), yet treatment failure occurs in 30% to 40% of patients. Those with BCG-unresponsive disease face a high risk of progression and represent a critical unmet need in urologic oncology. This review summarizes the mechanisms of BCG failure and evaluates emerging therapies for BCG-unresponsive NMIBC.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>We conducted a comprehensive literature review of clinical trials and preclinical studies through August 2025, focusing on therapeutic strategies for BCG-unresponsive NMIBC. Mechanisms of BCG resistance, regulatory definitions, and results from recent Phase II/III trials were analyzed.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Multiple novel therapies have demonstrated efficacy in BCG-unresponsive patients. Immune checkpoint inhibitors (e.g., pembrolizumab) achieved complete response (CR) rates of 41% in carcinoma in situ (CIS) patients. Gene therapies such as nadofaragene firadenovec and CG0070 induced CR rates of 51% and 75%, respectively. Device-assisted therapies including hyperthermic intravesical chemotherapy (HIVEC) showed 24-month recurrence-free survival of 57.4%. The IL-15 superagonist Anktiva (nogapendekin alfa inbakicept), recently FDA-approved, achieved a 71% CR rate with a median duration of 26.6 months when combined with BCG.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>The treatment landscape for BCG-unresponsive NMIBC is rapidly evolving, with immune checkpoint inhibitors, gene therapies, targeted agents, and advanced drug delivery systems showing promising efficacy. These innovations provide bladder-preserving options for patients ineligible for radical cystectomy. 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Mechanisms, Clinical Trials, and New Treatments for BCG-Unresponsive in Nonmuscle Invasive Bladder Cancer
Background
Bacillus Calmette–Guérin (BCG) is the standard adjuvant therapy for high-risk non-muscle invasive bladder cancer (NMIBC), yet treatment failure occurs in 30% to 40% of patients. Those with BCG-unresponsive disease face a high risk of progression and represent a critical unmet need in urologic oncology. This review summarizes the mechanisms of BCG failure and evaluates emerging therapies for BCG-unresponsive NMIBC.
Methods
We conducted a comprehensive literature review of clinical trials and preclinical studies through August 2025, focusing on therapeutic strategies for BCG-unresponsive NMIBC. Mechanisms of BCG resistance, regulatory definitions, and results from recent Phase II/III trials were analyzed.
Results
Multiple novel therapies have demonstrated efficacy in BCG-unresponsive patients. Immune checkpoint inhibitors (e.g., pembrolizumab) achieved complete response (CR) rates of 41% in carcinoma in situ (CIS) patients. Gene therapies such as nadofaragene firadenovec and CG0070 induced CR rates of 51% and 75%, respectively. Device-assisted therapies including hyperthermic intravesical chemotherapy (HIVEC) showed 24-month recurrence-free survival of 57.4%. The IL-15 superagonist Anktiva (nogapendekin alfa inbakicept), recently FDA-approved, achieved a 71% CR rate with a median duration of 26.6 months when combined with BCG.
Conclusions
The treatment landscape for BCG-unresponsive NMIBC is rapidly evolving, with immune checkpoint inhibitors, gene therapies, targeted agents, and advanced drug delivery systems showing promising efficacy. These innovations provide bladder-preserving options for patients ineligible for radical cystectomy. Future directions include biomarker-driven therapy selection, combination regimens, and optimized intravesical delivery platforms to improve long-term outcomes.
期刊介绍：
Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas:
Clinical Cancer Research
Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations
Cancer Biology:
Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery.
Cancer Prevention:
Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach.
Bioinformatics:
Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers.
Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.
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