Department of Urology, Amsterdam University Medical Centers, VU University, Postbus 7057, 1007, MB, Amsterdam, internal post address 4F-28, The Netherlands.
Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
BMC Cancer. 2021 Oct 29;21(1):1161. doi: 10.1186/s12885-021-08840-2.
The recommended treatment for patients with non-metastatic muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Following NAC, 20-40% of patients experience a complete pathological response (pCR) in the RC specimen and these patients have excellent long-term overall survival. Subject to debate is, however, whether patients with a pCR to NAC benefit from RC, which is a major surgical procedure with substantial morbidity, and if these patients might be candidates for close surveillance instead. However, currently it is not possible to accurately identify patients with a pCR to NAC in whom RC might be withheld. The objective of this study is to assess whether pathological response in the RC specimen after NAC can be predicted based on clinical, radiological, and histological variables and on a wide set of molecular biomarkers assessed in tissue, blood and urine.
This is a multicentre, prospective cohort study, including patients with cT2a-T4a N0-N1 M0 urothelial cell MIBC who are scheduled to undergo cisplatin-based NAC followed by RC. Prior to start of therapy, a 2-Deoxy-2-[18F] fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) is performed. Response to NAC is evaluated by CT-scan. Blood and urine, including cytology, are prospectively collected for biomarker analyses before and after NAC. Immediately before RC, participants undergo cystoscopy with bimanual examination and a re-staging transurethral resection (TUR) of all visible cancerous lesions or with biopsies from scar tissue. Subsequently, RC is performed in all patients. Tissue from the diagnostic TUR, the re-staging TUR, and the RC specimen is examined for the presence of urothelial cancer carcinoma and DNA and RNA is isolated for molecular analysis. The primary endpoint is the pathological stage (ypTN) in the RC and ePLND specimen and its association with clinical response.
If the PRE-PREVENCYS trial shows that the absence of residual disease after NAC in patients with MIBC is accurately predicted, a randomized controlled trial is scheduled comparing the overall survival of NAC plus RC versus NAC followed by close surveillance for patients with a clinically complete response (PREVENCYS trial).
Netherlands Trial Register: NL8678; Registered 20 May 2020 https://www.trialregister.nl/trial/8678.
对于非转移性肌层浸润性膀胱癌（MIBC）患者，推荐的治疗方法是新辅助化疗（NAC）和根治性膀胱切除术（RC）。在 NAC 后，20-40%的患者在 RC 标本中出现完全病理缓解（pCR），这些患者具有极好的长期总生存率。然而，存在争议的是，NAC 后出现 pCR 的患者是否受益于 RC，RC 是一种具有较大发病率的主要手术，如果这些患者可以作为密切监测的候选者，那么是否可以避免进行 RC。然而，目前尚无法准确识别可能需要保留 RC 的 NAC 后出现 pCR 的患者。本研究的目的是评估 NAC 后 RC 标本中的病理反应是否可以基于临床、影像学和组织学变量以及在组织、血液和尿液中评估的广泛分子生物标志物进行预测。
这是一项多中心、前瞻性队列研究，纳入了计划接受顺铂为基础的 NAC 后行 RC 的 cT2a-T4a N0-N1M0 尿路上皮细胞 MIBC 患者。在开始治疗前，进行 2-脱氧-2-[18F]氟脱氧葡萄糖（F-FDG）正电子发射断层扫描/计算机断层扫描（PET/CT）。通过 CT 扫描评估 NAC 的反应。在 NAC 前后，前瞻性收集血液和尿液，包括细胞学检查，用于生物标志物分析。在 RC 前，参与者行膀胱镜检查，进行双合诊检查和所有可见癌性病变的重新分期经尿道切除术（TUR）或瘢痕组织活检。随后，所有患者均行 RC。对诊断性 TUR、重新分期 TUR 和 RC 标本进行检查，以确定是否存在尿路上皮癌，并分离 DNA 和 RNA 进行分子分析。主要终点是 RC 和扩大盆腔淋巴结清扫术（ePLND）标本中的病理分期（ypTN）及其与临床反应的关系。
如果 PRE-PREVENCYS 试验表明 MIBC 患者 NAC 后无残留疾病的情况可以准确预测，计划进行一项随机对照试验，比较 NAC 加 RC 与 NAC 后密切监测具有临床完全缓解的患者的总生存率（PREVENCYS 试验）。
荷兰试验注册处：NL8678；注册日期 2020 年 5 月 20 日 https://www.trialregister.nl/trial/8678。
