Hasan Nazmul, Yang Daniel, Gibson Spencer, Khaleghi Barbod, Ziari Rozhan, Kalebasty Arash Rezazadeh
Department of Medicine, University of California, Irvine, CA 92868, USA.
Chao Family Comprehensive Cancer Center, Division of Hematology and Oncology, University of California, Irvine, CA 92868, USA.
Oncotarget. 2025 May 19;16:337-346. doi: 10.18632/oncotarget.28723.
Different treatment strategies are required for the non-muscle-invasive, muscle-invasive, and metastatic stages of bladder cancer. Standard treatments include surgery, chemotherapy, and radiation; however, they have their limitations. New discoveries have shown that combining immunotherapy and radiation treatment may improve patient outcomes. Radiation therapy promotes immunogenic cell death, which leads to antigen release and immune cell activation, whereas immunotherapy enhances the immune system's ability to recognize and destroy cancer cells by targeting checkpoint pathways like PD-1/PD-L1 and CTLA-4. This review examines the synergistic mechanisms of diverse modalities, focusing on their capacity to alter the tumor microenvironment and elicit systemic anti-tumor responses, such as the abscopal effect. Key clinical trials, such as BTCRC-GU15-023 and ANZUP, have demonstrated the efficacy and safety of combining these medications. However, difficulties persist, such as overlapping toxicities, unpredictability in patient responses, and a lack of accurate patient selection markers. Large-scale randomized trials are needed in the future to fine-tune treatment procedures, minimize toxicity, and validate predictive biomarkers such as PD-L1 expression and tumor mutation burden. By addressing these hurdles, the combination of radiation treatment and immunotherapy has the potential to change the bladder cancer therapeutic landscape.
膀胱癌的非肌肉浸润性、肌肉浸润性和转移性阶段需要不同的治疗策略。标准治疗方法包括手术、化疗和放疗;然而,它们都有其局限性。新的研究发现表明,免疫疗法与放射治疗相结合可能会改善患者的治疗效果。放射治疗可促进免疫原性细胞死亡,从而导致抗原释放和免疫细胞激活,而免疫疗法则通过靶向PD-1/PD-L1和CTLA-4等检查点通路来增强免疫系统识别和摧毁癌细胞的能力。本综述探讨了多种治疗方式的协同机制,重点关注它们改变肿瘤微环境和引发全身抗肿瘤反应(如远隔效应)的能力。关键临床试验,如BTCRC-GU15-023和ANZUP,已经证明了联合使用这些药物的有效性和安全性。然而,困难依然存在,如毒性重叠、患者反应不可预测以及缺乏准确的患者选择标志物。未来需要进行大规模随机试验,以优化治疗程序、将毒性降至最低,并验证诸如PD-L1表达和肿瘤突变负荷等预测性生物标志物。通过克服这些障碍,放射治疗与免疫疗法的联合应用有可能改变膀胱癌的治疗格局。