Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; University Vita-Salute San Raffaele, Milan, Italy.
Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; University Vita-Salute San Raffaele, Milan, Italy.
Eur Urol Oncol. 2021 Dec;4(6):1006-1010. doi: 10.1016/j.euo.2020.07.006. Epub 2020 Aug 23.
A 41-yr-old, otherwise healthy, premenopausal woman presented at our uro-oncology clinic with a diagnosis of muscle-invasive bladder cancer following a transurethral resection of the bladder performed at another center. After a thorough discussion with the patient, she was enrolled in the phase II PURE-01 trial (NCT02736266), testing three cycles of neoadjuvant pembrolizumab (200mg) every 3 wk before radical cystectomy. Before treatment, imaging studies were obtained as per the protocol using computed tomography (CT), [F]fluorodeoxyglucose positron emission tomography/CT, and multiparametric magnetic resonance imaging of the bladder, defining a clinically localized T2N0M0 stage. As per the protocol, potential biomarkers were assessed, including PD-L1 expression (84% combined positive score), tumor mutational burden (16.67 mut/Mb), and genomic profiling (FoundationONE assay; somatic mutation in TP53, EZH2, APC, TERT, CDKN1A, CDKN1B, and ARID1A genes, and truncation in BRCA2 gene). After immunotherapy, the patient underwent a robot-assisted radical cystectomy with extended pelvic lymph node dissection. The final pathology report revealed absence of residual disease (ie, pathological complete response, ypT0ypN0). During follow-up, the only relevant and permanent immune-mediated adverse event was hypothyroidism secondary to an autoimmune thyroiditis. It appeared 2 mo after radical cystectomy and it was managed successfully with hormonal replacement therapy. Two years after treatment, the patient is asymptomatic and free from disease recurrence. PATIENT SUMMARY: Increasing evidence suggests that frontline neoadjuvant immunotherapy may be beneficial for patients diagnosed with non-locally advanced, muscle-invasive bladder cancer (cT2N0), with fewer drawbacks than traditional chemotherapy. Although further studies are needed in support, this vision opens the opportunity for future clinical trials testing the potential incremental benefits of immunotherapy and the utility of novel biomarker- and imaging-based strategies to assess response to therapy.
一位 41 岁、健康状况良好、绝经前的女性，因在另一家中心进行的经尿道膀胱肿瘤切除术（TURBT）后诊断为肌层浸润性膀胱癌，在我院泌尿科肿瘤门诊就诊。在与患者进行了全面讨论后，她被纳入了 II 期 PURE-01 试验（NCT02736266），该试验在根治性膀胱切除术之前每 3 周接受三周期新辅助派姆单抗（200mg）治疗。在治疗前，按照方案进行了影像学研究，包括计算机断层扫描（CT）、[F]氟脱氧葡萄糖正电子发射断层扫描/CT 和膀胱多参数磁共振成像，定义了临床局限性 T2N0M0 期。按照方案，评估了潜在的生物标志物，包括 PD-L1 表达（84%联合阳性评分）、肿瘤突变负担（16.67 mut/Mb）和基因组分析（FoundationONE 检测；TP53、EZH2、APC、TERT、CDKN1A、CDKN1B 和 ARID1A 基因突变，BRCA2 基因突变）。免疫治疗后，患者接受了机器人辅助根治性膀胱切除术和扩大盆腔淋巴结清扫术。最终病理报告显示无残留疾病（即病理完全缓解，ypT0ypN0）。随访期间，唯一相关和永久性的免疫介导的不良事件是自身免疫性甲状腺炎引起的甲状腺功能减退症。它在根治性膀胱切除术后 2 个月出现，并用激素替代疗法成功治疗。治疗 2 年后，患者无症状且无疾病复发。患者总结：越来越多的证据表明，一线新辅助免疫治疗可能对诊断为非局部晚期、肌层浸润性膀胱癌（cT2N0）的患者有益，其缺点比传统化疗少。尽管还需要进一步的研究来支持，但这一观点为未来的临床试验提供了机会，以测试免疫治疗的潜在增量效益和新型生物标志物和基于成像的策略在评估治疗反应方面的效用。
