Singh Parminder, Black Peter
Division of Hematology and Oncology , Mayo clinic, Phoenix, AZ.
Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada.
Urol Oncol. 2016 Dec;34(12):548-555. doi: 10.1016/j.urolonc.2016.09.004. Epub 2016 Oct 21.
Checkpoint inhibitors have rapidly become a standard treatment option for metastatic urothelial carcinoma. A wave of enthusiasm for these drugs has pushed them also into the setting of localized bladder cancer, including both non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive disease bladder cancer (MIBC). Here, we aimed to review the emerging role of checkpoint inhibition in localized bladder cancer.
We reviewed the current treatment landscape for both NMIBC and MIBC and established a significant unmet clinical need for novel therapies. We have compiled the evidence that supports the investigation of checkpoint blockade in localized bladder cancer and have reviewed the corresponding clinical trial׳s landscape.
The success of checkpoint inhibitors in metastatic bladder cancer offers the most compelling rationale for testing checkpoint blockade in localized disease. The established benefit of intravesical Bacillus Calmette-Guérin provides precedent for immune therapy in bladder cancer. Immune dysfunction has been described in bladder cancer, and we know that checkpoint molecules are expressed in these tumors. Furthermore, the high neoantigen burden of bladder cancer and results from preclinical studies suggest that checkpoint blockade deserves testing in earlier stage disease. Multiple trials are either planned or underway in almost all bladder cancer disease states.
Ongoing trials would determine in the next several years whether checkpoint inhibitors can have a similar effect in localized disease as they have had in metastatic bladder cancer. They would also determine if patients with earlier disease would tolerate the toxicity of systemic therapy. The future holds promise for predictive biomarkers to guide individualized use of these agents and for effective combination therapies to overcome resistances.
检查点抑制剂已迅速成为转移性尿路上皮癌的标准治疗选择。对这些药物的一阵热情也将它们推向了局限性膀胱癌的治疗领域，包括非肌层浸润性膀胱癌（NMIBC）和肌层浸润性膀胱癌（MIBC）。在此，我们旨在综述检查点抑制在局限性膀胱癌中的新兴作用。
我们回顾了NMIBC和MIBC目前的治疗情况，并确定了对新疗法存在重大未满足的临床需求。我们收集了支持在局限性膀胱癌中研究检查点阻断的证据，并回顾了相应的临床试验情况。
检查点抑制剂在转移性膀胱癌中的成功为在局限性疾病中测试检查点阻断提供了最有说服力的理由。膀胱内卡介苗已确立的益处为膀胱癌的免疫治疗提供了先例。膀胱癌中已描述了免疫功能障碍，并且我们知道这些肿瘤中表达检查点分子。此外，膀胱癌的高新生抗原负荷和临床前研究结果表明检查点阻断值得在早期疾病中进行测试。几乎在所有膀胱癌疾病状态下都有多项试验正在计划或进行中。
正在进行的试验将在未来几年确定检查点抑制剂在局限性疾病中是否能产生与在转移性膀胱癌中类似的效果。它们还将确定早期疾病患者是否能耐受全身治疗的毒性。未来有望出现预测性生物标志物来指导这些药物的个体化使用，以及有效的联合疗法来克服耐药性。
