Department of Urology. General Hospital of Athens "G.N.A. G. Gennimatas". Athens. Greece.
2nd Propaedeutic Department of Internal Medicine. ATTIKON University Hospital. Medical School. National & Kapodistrian University of Athens. Athens. Greece.
Arch Esp Urol. 2021 Sep;74(7):681-691.
Most patients at first diagnosis of bladder cancer (BC) present with non muscle invasive disease (NMIBC). BCG intravesical therapy after transurethral resection of the bladder tumor is the gold standard in intermediate and high risk NMIBC patients. However, it is estimated that approximately 50% of these patients will present with BCG failure which increases their risk for progression to muscle invasive disease. Currently, the best option for these patients is radical cystectomy. Thus, it is of great interest to pursue new, therapeutic options for BCG failure patients to avoid the necessity of radical cystectomy. We hereby review novel treatment modalities for BCG failure patients. METHODS: This is a narrative review. Keywords for the search were BCG failure, BCG unresponsive, BCG refractory, BCG relapsing and BCG intolerance. Evidence was identified through a search for publications with a ''BCG unresponsive'' tag through 2020. Studies were selected if they contained clinical data on BCG unresponsive therapeutics with near-term availability. Clinical trial landscape evaluation for emerging therapies was performed by searching ClinicalTrials.gov for recruiting/ open interventional trials in 2020. RESULTS: Novel treatment modalities for BCG failure include intravesical chemotherapy, BCG re-challenge or combination of BCG with IFN-α2β, valrubicin, radiotherapy, electromotive drug administration, vicinium, chemohyperthermia, photodynamic therapy, gene therapy, vaccine therapy and immunotherapy. For patients in whom BCG has once failed a repeat course of BCG or BCG plus interferon appears to be a reasonable practice. Likewise, single agent gemcitabine may be considered a treatment modality. However, after 2 or more BCG failures, especially in patients with earlier relapses or cancer persistence, single agent intravesical chemotherapy with valrubicin, gemcitabine or docetaxel appears to be less active than doublet/triplet intravesical chemotherapy or mitomycin chemothermotherapy. Gene therapy or conjugated antibodies may play a role upon further relapse. Single agent pembrolizumab is unlikely to be used as first line, but may be useful, along with multiple new immunotherapeutics, as part of a multimodal approach towards BCG unresponsive disease. CONCLUSIONS: Results from ongoing trials will provide us useful information about many of the existing regimens and probably new drugs will soon be available for this group of patients.
大多数膀胱癌（BC）患者在初次诊断时表现为非肌肉浸润性疾病（NMIBC）。BCG 膀胱内治疗是中高危 NMIBC 患者的金标准，适用于经尿道膀胱肿瘤切除术（TURBT）后。然而，据估计，大约 50%的这些患者将出现 BCG 治疗失败，这增加了他们进展为肌肉浸润性疾病的风险。目前，这些患者的最佳选择是根治性膀胱切除术。因此，对于 BCG 治疗失败的患者，寻求新的治疗方法以避免需要根治性膀胱切除术是非常重要的。本文回顾了 BCG 治疗失败患者的新治疗方法。
这是一篇叙述性综述。检索的关键词是 BCG 治疗失败、BCG 无反应、BCG 耐药、BCG 复发和 BCG 不耐受。通过搜索带有“BCG 无反应”标签的出版物，在 2020 年确定了证据。如果研究包含了 BCG 无反应治疗的临床数据，且这些治疗方法具有近期可用性，则选择这些研究。通过在 ClinicalTrials.gov 上搜索 2020 年正在招募/开放的干预性试验，对新兴疗法的临床试验进行了评估。
BCG 治疗失败的新治疗方法包括膀胱内化疗、BCG 再挑战或 BCG 与 IFN-α2β、戊柔比星、放疗、电药物传递、vicinium、化学热疗、光动力疗法、基因治疗、疫苗治疗和免疫治疗联合使用。对于曾经接受过 BCG 治疗但失败的患者，重复使用 BCG 或 BCG 联合干扰素似乎是一种合理的治疗方法。同样，单药吉西他滨也可被视为一种治疗方法。然而，在出现 2 次或更多次 BCG 治疗失败后，特别是在更早复发或癌症持续存在的患者中，与双药/三药膀胱内化疗或丝裂霉素化学疗法相比，单药膀胱内化疗用戊柔比星、吉西他滨或多西他赛的疗效似乎较差。基因治疗或结合抗体可能在进一步复发时发挥作用。单药 pembrolizumab 不太可能作为一线治疗药物，但可能与多种新的免疫治疗药物一起，作为针对 BCG 无反应性疾病的多模式方法的一部分，发挥作用。
正在进行的试验的结果将为我们提供许多现有方案的有用信息，而且可能很快就会有新的药物可供这组患者使用。
