全身性免疫治疗
免疫疗法已成为对抗有助于肿瘤细胞逃避的检查点蛋白抑制剂的目标。针对细胞程序性死亡蛋白-1 (PD-1) 和程序性死亡配体 1 (PD-L1) 抑制剂的研究最有成效。[74]Bellmunt J, Powles T, Vogelzang NJ. A review on the evolution of PD-1/PD-L1 immunotherapy for bladder cancer: the future is now. Cancer Treat Rev. 2017;54:58-67.http://www.sciencedirect.com/science/article/pii/S0305737217300075?via%3Dihubhttp://www.ncbi.nlm.nih.gov/pubmed/28214651?tool=bestpractice.com 正在针对新型 PD-1/PD-L1 抗体、细胞毒性 T 淋巴细胞相关蛋白 4 (CTLA-4) 抑制剂、联合检查点抑制剂以及检查点抑制剂与标准化疗药物的联合使用进行临床试验。[86]Farina MS, Lundgren KT, Bellmunt J. Immunotherapy in urothelial cancer: recent results and future perspectives. Drugs. 2017;77:1077-89.http://www.ncbi.nlm.nih.gov/pubmed/28493171?tool=bestpractice.com 一种新型药物是血管内皮生长因子受体-2 (vascular endothelial growth factor receptor-2, VEGFR-2) 拮抗剂。一项关于雷莫芦单抗联用多西他赛的研究显示，对于铂类难治的晚期尿路上皮癌患者，与单用多西他赛相比，雷莫芦单抗联用多西他赛能延长无进展生存期。[87]Petrylak DP, de Wit R, Chi KN, et al; RANGE study investigators. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial. Lancet. 2017 Nov 18;390(10109):2266-2277.http://www.ncbi.nlm.nih.gov/pubmed/28916371?tool=bestpractice.com 针对非肌层浸润性膀胱癌的系统性免疫疗法的临床试验正在进行中。
戊柔比星
戊柔比星是多柔比星的衍生物，且是唯一被批准用于治疗对 BCG 无反应的原位癌膀胱灌注治疗药物。因其在原始配方中混入杂质，于 2002 年撤出市场。这些问题得到解决后，该药物已重新上市。[88]FDA. Manufacturing issues remain for Indevus' Valstar. January 2008. http://fdanews.com/ (last accessed 7 August 2017).http://fdanews.com/newsletter/article?issueId=11203&articleId=103010 在极高危患者中，多达三分之一的患者可从中获益。[89]Steinberg G, Bahnson R, Brosman S, et al. Efficacy and safety of valrubicin for the treatment of Bacillus Calmette-Guerin refractory carcinoma in situ of the bladder. J Urol. 2000;163:761-767.http://www.ncbi.nlm.nih.gov/pubmed/10687972?tool=bestpractice.com
微波热疗
在随机临床试验中，丝裂霉素结合微波热疗优于单独使用丝裂霉素，而且 94% 的原位癌患者产生完全反应。可在欧洲使用，但美国尚未批准使用。[90]Colombo R, Da Pozzo LF, Salonia A, et al. Multicentric study comparing intravesical chemotherapy alone and with local microwave hyperthermia for prophylaxis of recurrence of superficial transitional cell carcinoma. J Clin Oncol. 2003;21:4270-4276.http://www.ncbi.nlm.nih.gov/pubmed/14581436?tool=bestpractice.com[91]Witjes JA, Hendricksen K, Gofrit O, et al. Intravesical hyperthermia and mitomycin-C for carcinoma in situ of the urinary bladder: experience of the European Synergo working party. World J Urol. 2009;27:319-324.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694311/pdf/345_2009_Article_384.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/19234857?tool=bestpractice.com[92]Sylvester RJ, Brausi MA, Hoelti W, et al. Long-term efficacy results of EORTC GU Group study 30911 comparing epirubicin, bacillus Calmette-Guérin (BCG), and BCG plus isoniazid in patients with intermediate and high-risk stage TaT1 papillary carcinoma of the bladder. Eur Urol Suppl. 2008;7:298.
多西他赛
虽然未批准使用多烯紫杉醇进行膀胱灌注，但其膀胱灌注的耐受性好，而且单独使用与联合丝裂霉素和多柔比星使用均有效。[13]Grossman HB, O'Donnell MA, Cookson MS, et al. Bacillus Calmette-Guérin failures and beyond: contemporary management of non-muscle-invasive bladder cancer. Rev Urol. 2008;10:281-289.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615101/http://www.ncbi.nlm.nih.gov/pubmed/19145271?tool=bestpractice.com[51]Colombel M, Soloway M, Akazac H, et al. Epidemiology, staging, grading, and risk stratification of bladder Cancer. Eur Urol Suppl. 2008;7:618-626.http://eu-acme.org/europeanurology/upload_articles/Colombel.pdf[93]Barlow L, McKiernan J, Saawczuk I, et al. A single-institution experience with induction and maintenance intravesical docetaxel in the management of non-muscle-invasive bladder cancer refractory to Bacille Calmette-Guérin therapy. BJU Int. 2009;104:1098-1102.http://www.ncbi.nlm.nih.gov/pubmed/19389012?tool=bestpractice.com
吉西他滨
虽然未批准使用吉西他滨进行膀胱灌注，但其膀胱灌注的耐受性好，而且单独和联合丝裂霉素和多柔比星使用均有效。[13]Grossman HB, O'Donnell MA, Cookson MS, et al. Bacillus Calmette-Guérin failures and beyond: contemporary management of non-muscle-invasive bladder cancer. Rev Urol. 2008;10:281-289.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615101/http://www.ncbi.nlm.nih.gov/pubmed/19145271?tool=bestpractice.com[51]Colombel M, Soloway M, Akazac H, et al. Epidemiology, staging, grading, and risk stratification of bladder Cancer. Eur Urol Suppl. 2008;7:618-626.http://eu-acme.org/europeanurology/upload_articles/Colombel.pdf[93]Barlow L, McKiernan J, Saawczuk I, et al. A single-institution experience with induction and maintenance intravesical docetaxel in the management of non-muscle-invasive bladder cancer refractory to Bacille Calmette-Guérin therapy. BJU Int. 2009;104:1098-1102.http://www.ncbi.nlm.nih.gov/pubmed/19389012?tool=bestpractice.com[94]Skinner EC, Goldman B, Sakr WA, et al. SWOG S0353: Phase II trial of intravesical gemcitabine in patients with nonmuscle invasive bladder cancer and recurrence after 2 prior courses of intravesical bacillus Calmette-Guérin. J Urol. 2013;190:1200-4.http://www.ncbi.nlm.nih.gov/pubmed/23597452?tool=bestpractice.com
吉西他滨加膀胱内多西紫杉醇
对卡介苗 (BCG) 疫苗或标准膀胱灌注化疗无反应的患者，通常使用吉西他滨后再立即使用膀胱内多西紫杉醇可得到有效抢救。[95]Steinberg RL, Thomas LJ, O’Donnell MA, et al. Sequential intravesical gemcitabine and docetaxel for the salvage treatment of non-muscle invasive bladder cancer. Bladder Cancer. 2015;1:65-72.http://content.iospress.com/articles/bladder-cancer/blc0008
