Osanto Susanne, Álvarez Gómez de Segura Cristina
Department of Oncology. Leiden University Medical Center. Leiden. The Netherlands. European Uro-Oncology Group (EUOG). Leiden. The Netherlands.
Arch Esp Urol. 2020 Dec;73(10):971-985.
Fifty percent of muscle-invasive bladder cancer (MIBC) patients succumb from metastatic disease despite radical cystectomy (RC). Neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (ACT) randomized clinical trials (RCT) investigated whether peri-operative chemotherapy improves survival. More recently, immune checkpoint inhibitors (ICI) are explored as peri-operative single agent, ICI-ICI or ICI-chemotherapy combinations. Our goal is to provide the status of neoadjuvant and adjuvant treatment in MIBC.
The literature on NAC and ACT trials in MIBC was reviewed.
Since the 1980s, NAC RCTs were performed in cisplatin-fit patients, mainly using cisplatin combination chemotherapy. Meta-analyses indicated a small, but significant 5% improvement in overall survival in T2-T4N0M0 MIBC patients. Mostly MVAC or gemcitabine-cisplatin (GC) regimens were used without clear benefit of one regimen over the other. NAC value in N+MIBC is not established and predictive value of associated~25-40% complete downstaging (pathologically confirmed complete regression, pCR) not unequivocally demonstrated. Adjuvant cisplatin-based chemotherapy RCTs were smaller, some prematurely stopped for poor accrual, and underpowered to demonstrate clear statistical evidence for a 5% overall survival advantage in pT3-T4N1-3M0 MIBC. Novel neoadjuvant immune checkpoint inhibitors, alone or with chemotherapy, phase 2 trials demonstrate down staging and encouraging clinical results.
Neoadjuvant MVAC or GC in cT2-T4N0 MIBC patients fit for cisplatin is still recommended based on OS benefit shown in meta-analyses, butreal-world adherence to NAC is low as ~40-50% ofpatients are unfit for cisplatin. The value of neoadjuvant treatment in node-positive MIBC is not clearly demonstrated requiring more accurate clinical staging and prospective studies. Adjuvant cisplatin-based chemotherapy may be considered in selected, chemo-naïve pT3-T4N+patients. Results from prospective checkpoint inhibitor immunotherapy RCTs are needed before immunotherapy becomes a recommended alternative for peri-operative treatment. Molecular tumour subtyping will support selecting novel agents for neoadjuvant or adjuvant strategies.
尽管进行了根治性膀胱切除术（RC），仍有50%的肌层浸润性膀胱癌（MIBC）患者死于转移性疾病。新辅助化疗（NAC）和辅助化疗（ACT）的随机临床试验（RCT）研究了围手术期化疗是否能提高生存率。最近，免疫检查点抑制剂（ICI）被探索作为围手术期单药、ICI-ICI或ICI-化疗联合用药。我们的目标是提供MIBC新辅助和辅助治疗的现状。
回顾了关于MIBC中NAC和ACT试验的文献。
自20世纪80年代以来，在适合顺铂治疗的患者中进行了NAC RCT，主要使用顺铂联合化疗。荟萃分析表明，T2-T4N0M0 MIBC患者的总生存率有小幅但显著的5%的提高。大多使用MVAC或吉西他滨-顺铂（GC）方案，且一种方案相对于另一种方案没有明显优势。NAC在N+MIBC中的价值尚未确立，相关的25%-40%完全降期（病理证实完全缓解，pCR）的预测价值也未得到明确证实。基于顺铂的辅助化疗RCT规模较小，一些因入组不佳而提前终止，且样本量不足以证明pT3-T4N1-3M0 MIBC患者总生存率有5%的优势有明确的统计学证据。新的新辅助免疫检查点抑制剂，单独或与化疗联合，2期试验显示有降期效果且临床结果令人鼓舞。
基于荟萃分析显示的总生存获益，仍建议对适合顺铂治疗的cT2-T4N0 MIBC患者进行新辅助MVAC或GC治疗，但实际中NAC的依从性较低，因为约40%-50%的患者不适合顺铂治疗。新辅助治疗在淋巴结阳性MIBC中的价值尚未明确证实，需要更准确的临床分期和前瞻性研究。对于选定的、未接受过化疗的pT3-T4N+患者，可考虑基于顺铂的辅助化疗。在免疫治疗成为围手术期治疗的推荐替代方案之前，需要前瞻性检查点抑制剂免疫治疗RCT的结果。分子肿瘤亚型分析将有助于为新辅助或辅助治疗策略选择新型药物。
