CONTEXT Bacillus Calmette-Guérin (BCG) is currently the most effective intravesical therapy for nonmuscle invasive bladder cancer, reducing not only recurrence rates but also preventing progression and reducing deaths. However, response rates to BCG vary widely and are dependent on a multitude of factors. OBJECTIVE To review existing data on clinical, pathologic, immune, and molecular markers that allow prediction of BCG response. EVIDENCE ACQUISITION PubMed and MEDLINE search of English language literature was conducted from its inception to July 2017 using appropriate search terms. Following systematic literature review and analysis of data, consensus voting was used to generate the content of this review. EVIDENCE SYNTHESIS As seen in the EORTC and CUETO risk nomograms, clinicopathologic features, especially tumor stage and grade, are the most effective predictors of BCG response. Data are less robust with regards to the association of response with age, female sex, recurrent tumors, multiplicity of tumors, and the presence of carcinoma in situ. Single biomarkers, such as tumor p53 and urinary interleukin-2 expression, have had limited success in predicting BCG response, possibly due to the multifaceted nature of the generated immune response. More comprehensive biomarker panels (eg, urinary cytokines), have a more robust correlation with response, as do patterns of urinary cytologic fluorescent in-situ hybridization examination. Gene expression data correlate with disease progression, but studies examining potential associations with BCG response are limited. CONCLUSIONS Currently, the best predictors of BCG response are clinicopathologic features such as tumor grade and stage. Panels of urinary cytokines, as well as fluorescent in-situ hybridization patterns of cytologic anomalies, appear to be promising biomarkers. The complexity of the immune response to BCG and the heterogeneity of bladder cancer suggest that future studies should amalgamate measures reflecting innate immune response and tumor/stromal gene expression before these can be adopted for clinical use. PATIENT SUMMARY Bacillus Calmette-Guérin (BCG) immunotherapy is an effective treatment for many patients with nonmuscle invasive bladder cancer. An individual's response to BCG can be predicted by using various features of the cancer. In the future, predictive markers using molecular measures of the tumor type and the immune response to BCG may allow us to precisely know an individual's likely outcome after BCG treatment.

中文翻译：

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预测膀胱内芽孢杆菌Calmette-Guérin免疫疗法的反应：我们还存在吗？系统评价。

上下文卡介苗芽孢杆菌（BCG）是目前非肌肉浸润性膀胱癌最有效的膀胱内治疗，不仅可以降低复发率，而且可以预防进展并减少死亡。但是，对卡介苗的反应率差异很大，并且取决于多种因素。目的回顾有关临床，病理，免疫和分子标志物的现有数据，以预测卡介苗反应。证据获取PubMed和MEDLINE从开始到2017年7月使用适当的搜索词对英语文学进行了搜索。在进行系统的文献综述和数据分析之后，使用共识投票来产生本评论的内容。证据综合从EORTC和CUETO风险诺模图中可以看出，临床病理特征，尤其是肿瘤的分期和等级，是BCG反应最有效的预测因子。关于反应与年龄，女性，复发性肿瘤，肿瘤的多样性以及原位癌的存在之间的关系，数据不那么可靠。单一的生物标志物，例如肿瘤p53和尿液白细胞介素2的表达，在预测BCG反应方面的成功有限，这可能是由于所产生的免疫反应的多面性所致。更为全面的生物标志物检测组（例如尿液细胞因子）与反应的相关性更强，尿液细胞学荧光原位杂交检查的模式也是如此。基因表达数据与疾病进展相关，但是研究与BCG反应潜在联系的研究有限。结论目前，BCG反应的最佳预测指标是临床病理特征，例如肿瘤的分级和分期。尿细胞因子组以及细胞学异常的荧光原位杂交模式似乎是有前途的生物标志物。对BCG的免疫反应的复杂性和膀胱癌的异质性表明，未来的研究应合并反映先天免疫反应和肿瘤/基质基因表达的措施，然后才能将其用于临床。患者摘要卡介苗芽孢杆菌（BCG）免疫疗法是许多非肌肉浸润性膀胱癌患者的有效治疗方法。可以通过使用癌症的各种特征来预测个人对BCG的反应。将来，