Pietro Scilipoti, Mattia Longoni, Mario de Angelis, Paolo Zaurito, Aleksander Ślusarczyk, Francesco Soria, Benjamin Pradere, Wojciech Krajewski, David D'Andrea, Andrea Mari, Francesco Del Giudice, Renate Pichler, José Daniel Subiela, Gautier Marcq, Andrea Gallioli, Luca Afferi, Riccardo Mastroianni, Giuseppe Simone, Simone Albisinni, Laura S Mertens, Ekaterina Laukhtina, Katharina Oberneder, José Luis Rodríguez Elena, Javier Aranda, Alfonso Lafuente Puentedura, Jorge Caño Velasco, Roberto Contieri, Rodolfo Hurle, Keiichiro Mori, Piotr Radziszewski, Shahrokh F Shariat, Paolo Gontero, Andrea Necchi, Morgan Rouprêt, Francesco Montorsi, Andrea Salonia, Alberto Briganti, Marco Moschini
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There are limited comparisons of long-term outcomes between adequate and inadequate BCG.</p><p><strong>Methods: </strong>We analyzed data from a multicenter European database (2010-2024) for 1558 patients diagnosed with IR- or HiR-NMIBC who underwent BCG treatment and received at least five BCG instillations. Adequate BCG was defined as at least five of six induction instillations and two of three maintenance doses, or two of six doses of a reinduction course. A 3-mo landmark analysis was conducted. Recurrence-free survival (RFS), high-grade RFS (HG-RFS), progression-free survival (PFS), and overall survival (OS) were estimated using inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and IPTW-adjusted multivariable Cox regression models. Cancer-specific mortality (CSM) was assessed via cumulative incidence curves and Fine-Gray competing-risks regression analysis.</p><p><strong>Key findings and limitations: </strong>The cohort included 606 IR-NMIBC (39%), 840 HiR-NMIBC (54%), and 112 very HiR (VHR)-NMIBC (7.1%) cases. Adequate BCG was administered to 1226 patients (78%). Among 1239 patients (80%) with documented treatment termination reasons, 503 (41%) completed guideline-recommended treatment and 150 (12%) discontinued because of BCG intolerance. Over median follow-up of 37 mo, adequate BCG was associated with higher IPTW-adjusted 5-yr RFS (72% vs 52%; hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.31-0.85; p < 0.001), HG-RFS (83% vs 68%; HR 0.43, 95% CI 0.32-0.58; p < 0.001), PFS (92% vs 85%; HR 0.47, 95% CI 0.30-0.74; p = 0.001), and OS (88% vs 71%; HR 0.52, 95% CI 0.37-0.74; p = 0.001). CSM rates were comparable between the groups (3% vs 4.9%; p = 0.3).</p><p><strong>Conclusions and clinical implications: </strong>Adequate BCG, as defined by the International Bladder Cancer Group (IBCG), was associated with significantly better RFS, PFS, and OS. These findings support use of the IBCG definition as a standardized benchmark for BCG exposure. However, further prospective validation to confirm causality is needed.</p>","PeriodicalId":12160,"journal":{"name":"European urology focus","volume":" ","pages":""},"PeriodicalIF":5.6000,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Long-term Oncological Outcomes for Patients with Non-muscle-invasive Bladder Cancer Treated with Bacillus Calmette-Guérin (BCG): A Comparative Analysis of Adequate Versus Inadequate BCG Treatment.\",\"authors\":\"Pietro Scilipoti, Mattia Longoni, Mario de Angelis, Paolo Zaurito, Aleksander Ślusarczyk, Francesco Soria, Benjamin Pradere, Wojciech Krajewski, David D'Andrea, Andrea Mari, Francesco Del Giudice, Renate Pichler, José Daniel Subiela, Gautier Marcq, Andrea Gallioli, Luca Afferi, Riccardo Mastroianni, Giuseppe Simone, Simone Albisinni, Laura S Mertens, Ekaterina Laukhtina, Katharina Oberneder, José Luis Rodríguez Elena, Javier Aranda, Alfonso Lafuente Puentedura, Jorge Caño Velasco, Roberto Contieri, Rodolfo Hurle, Keiichiro Mori, Piotr Radziszewski, Shahrokh F Shariat, Paolo Gontero, Andrea Necchi, Morgan Rouprêt, Francesco Montorsi, Andrea Salonia, Alberto Briganti, Marco Moschini\",\"doi\":\"10.1016/j.euf.2025.04.033\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objective: </strong>Intravesical bacillus Calmette-Guérin (BCG) instillation is recommended for intermediate-risk (IR) and high-risk (HiR) non-muscle-invasive bladder cancer (NMIBC). There are limited comparisons of long-term outcomes between adequate and inadequate BCG.</p><p><strong>Methods: </strong>We analyzed data from a multicenter European database (2010-2024) for 1558 patients diagnosed with IR- or HiR-NMIBC who underwent BCG treatment and received at least five BCG instillations. Adequate BCG was defined as at least five of six induction instillations and two of three maintenance doses, or two of six doses of a reinduction course. A 3-mo landmark analysis was conducted. Recurrence-free survival (RFS), high-grade RFS (HG-RFS), progression-free survival (PFS), and overall survival (OS) were estimated using inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and IPTW-adjusted multivariable Cox regression models. 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引用次数: 0
摘要
背景与目的：膀胱内卡介苗（BCG）被推荐用于治疗中危（IR）和高危（HiR）非肌肉浸润性膀胱癌（NMIBC）。卡介苗充足和不充足之间的长期结果比较有限。方法：我们分析了来自欧洲多中心数据库（2010-2024）的1558例诊断为IR或IR- nmibc的患者的数据，这些患者接受了卡介苗治疗并接受了至少5次卡介苗注射。适当的卡介苗被定义为6次诱导注射中至少5次，3次维持剂量中至少2次，或6次再诱导过程中至少2次。进行3个月的里程碑分析。使用治疗加权逆概率（IPTW）调整的Kaplan-Meier曲线和IPTW调整的多变量Cox回归模型估计无复发生存期（RFS）、高级别生存期（HG-RFS）、无进展生存期（PFS）和总生存期（OS）。通过累积发病率曲线和Fine-Gray竞争风险回归分析评估癌症特异性死亡率（CSM）。主要发现和局限性：该队列包括606例IR-NMIBC(39%)， 840例IR-NMIBC（54%）和112例very HiR (VHR)-NMIBC（7.1%）。1226例患者（78%）接受足量卡介苗治疗。在1239例（80%）有治疗终止原因的患者中，503例（41%）完成了指南推荐的治疗，150例（12%）因卡介苗不耐受而停止治疗。在37个月的中位随访中，适当的BCG与更高的iptw调整后的5年RFS相关(72% vs 52%；风险比[HR] 0.40, 95%可信区间[CI] 0.31-0.85；结论和临床意义：根据国际膀胱癌组织（IBCG）的定义，适当的卡介苗与更好的RFS、PFS和OS相关。这些发现支持使用IBCG定义作为BCG暴露的标准化基准。然而，需要进一步的前瞻性验证来确认因果关系。
Long-term Oncological Outcomes for Patients with Non-muscle-invasive Bladder Cancer Treated with Bacillus Calmette-Guérin (BCG): A Comparative Analysis of Adequate Versus Inadequate BCG Treatment.
Background and objective: Intravesical bacillus Calmette-Guérin (BCG) instillation is recommended for intermediate-risk (IR) and high-risk (HiR) non-muscle-invasive bladder cancer (NMIBC). There are limited comparisons of long-term outcomes between adequate and inadequate BCG.
Methods: We analyzed data from a multicenter European database (2010-2024) for 1558 patients diagnosed with IR- or HiR-NMIBC who underwent BCG treatment and received at least five BCG instillations. Adequate BCG was defined as at least five of six induction instillations and two of three maintenance doses, or two of six doses of a reinduction course. A 3-mo landmark analysis was conducted. Recurrence-free survival (RFS), high-grade RFS (HG-RFS), progression-free survival (PFS), and overall survival (OS) were estimated using inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and IPTW-adjusted multivariable Cox regression models. Cancer-specific mortality (CSM) was assessed via cumulative incidence curves and Fine-Gray competing-risks regression analysis.
Key findings and limitations: The cohort included 606 IR-NMIBC (39%), 840 HiR-NMIBC (54%), and 112 very HiR (VHR)-NMIBC (7.1%) cases. Adequate BCG was administered to 1226 patients (78%). Among 1239 patients (80%) with documented treatment termination reasons, 503 (41%) completed guideline-recommended treatment and 150 (12%) discontinued because of BCG intolerance. Over median follow-up of 37 mo, adequate BCG was associated with higher IPTW-adjusted 5-yr RFS (72% vs 52%; hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.31-0.85; p < 0.001), HG-RFS (83% vs 68%; HR 0.43, 95% CI 0.32-0.58; p < 0.001), PFS (92% vs 85%; HR 0.47, 95% CI 0.30-0.74; p = 0.001), and OS (88% vs 71%; HR 0.52, 95% CI 0.37-0.74; p = 0.001). CSM rates were comparable between the groups (3% vs 4.9%; p = 0.3).
Conclusions and clinical implications: Adequate BCG, as defined by the International Bladder Cancer Group (IBCG), was associated with significantly better RFS, PFS, and OS. These findings support use of the IBCG definition as a standardized benchmark for BCG exposure. However, further prospective validation to confirm causality is needed.
期刊介绍：
European Urology Focus is a new sister journal to European Urology and an official publication of the European Association of Urology (EAU).
EU Focus will publish original articles, opinion piece editorials and topical reviews on a wide range of urological issues such as oncology, functional urology, reconstructive urology, laparoscopy, robotic surgery, endourology, female urology, andrology, paediatric urology and sexual medicine. The editorial team welcome basic and translational research articles in the field of urological diseases. Authors may be solicited by the Editor directly. All submitted manuscripts will be peer-reviewed by a panel of experts before being considered for publication.
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