根据当前的世界卫生组织（WHO）标准，对肌浸润性膀胱癌（MIBC）的评分存在争议，因其预后价值有限。除少数个案外，所有MIBC病例均属于高级别。为了开发一种融合组织形态学表型、肿瘤周围间质淋巴细胞（sTILs）、肿瘤嵌套及生长和扩散模式的预后组织学评分系统，我们收集了484例接受囊肿切除术和淋巴清扫术的患者的组织标本和临床数据，有或没有辅助化疗治疗。组织形态学表型、sTILs、肿瘤嵌套及生长和扩散模式等进行评估，并分为四个评分组（GG）。我们将GG与分子亚型、免疫浸润、免疫检查点表达、细胞外基质（ECM）重塑和上皮间质转化（EMT）活性进行相关性分析。GG在单变量和多变量分析中与总生存期（OS）、疾病特异性生存期（DSS）和无进展生存期（PFS）相关。通过描述性统计分析与生物特征的关联。该新的GG，将两个组织形态学肿瘤组、三个sTILs组、三个肿瘤嵌套组和四个生长/扩散模式融合在一起，单变量存活分析（OS，DSS和PFS）中具有显著性。通过多变量Cox回归分析，证实GG作为独立的预后预测因子，效果最佳。与分子数据的相关性显示从GG1到GG4逐渐从基底型向腺上皮型过渡，生存期、免疫浸润和免疫检查点活性逐渐减少，ECM重塑和EMT活性逐渐增加。我们提出了一种新颖的、与预后相关的、基于生物学的MIBC评分系统，在常规病理切片中适用于囊肿切除术。我们开发了一种新颖的方法来评估晚期膀胱癌的侵袭性，与目前世界卫生组织提出的方法相比，可提供更好的风险分层。版权所有© 2023 The Authors。由Elsevier B.V.出版。保留所有权利。

Grading of muscle-invasive bladder cancer (MIBC) according to the current World Health Organization (WHO) criteria is controversial due to its limited prognostic value. All MIBC cases except a tiny minority are of high grade.To develop a prognostic histological scoring system for MIBC integrating histomorphological phenotype, stromal tumor-infiltrating lymphocytes (sTILs), tumor budding, and growth and spreading patterns.Tissue specimens and clinical data of 484 patients receiving cystectomy and lymphadenectomy with curative intent with or without adjuvant chemotherapy. Histomorphological phenotypes, sTILs, tumor budding, and growth and spreading patterns were evaluated and categorized into four grade groups (GGs). GGs were correlated with molecular subtypes, immune infiltration, immune checkpoint expression, extracellular matrix (ECM) remodeling, and epithelial-mesenchymal transition (EMT) activity.GGs were associated with overall (OS), disease-specific (DSS), and progression-free (PFS) survival in univariable and multivariable analyses. Association with biological features was analyzed with descriptive statistics.Integration of two histomorphological tumor groups, three sTILs groups, three tumor budding groups, and four growth/spread patterns yielded four novel GGs that had high significance in the univariable survival analysis (OS, DSS, and PFS). GGs were confirmed as independent prognostic predictors with the greatest effect in the multivariable Cox regression analysis. Correlation with molecular data showed a gradual transition from basal to luminal subtypes from GG1 to GG4; a gradual decrease in survival, immune infiltration, and immune checkpoint activity; and a gradual increase in ECM remodeling and EMT activity.We propose a novel, prognostically relevant, and biologically based scoring system for MIBC in cystectomies applicable to routine pathological sections.We developed a novel approach to assess the aggressiveness of advanced bladder cancer, which allows improved risk stratification compared with the method currently proposed by the World Health Organization.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.