Department of Urology, Hospital Center Biel, Spitalzentrum Biel, Vogelsang 84, 2501, Biel, Switzerland.
Department for BioMedical Research, Translational Organoid Resource Core, University of Bern, Bern, Switzerland.
BMC Urol. 2023 May 11;23(1):89. doi: 10.1186/s12894-023-01262-1.
In intermediate-risk non-muscle invasive bladder cancer (NMIBC) clinical guidelines suggest an adjuvant instillation with a chemotherapeutic agent. However, the agent and regimen are not clearly defined. Worldwide, less than 15% of patients receive this adjuvant chemotherapeutic instillation. We recently developed a pipeline for the generation of patient derived organoids (PDO) in NMIBC. In this phase II trial, we aim to use our in vitro pipeline to select the most effective drug for chemotherapeutic instillation in NMIBC patients.
Patients with first diagnosis of intermediate-risk NMIBC that are directed to transurethral resection of bladder tumor (TURBT) are enrolled. During TURBT, tumor is sampled, and specimens are directed to generate PDO. Once the PDO are formed, drug screens on them for Epirubicin, Mitomycin C, Gemcitabine and Docetaxel are performed. The drug with the highest antitumor activity in vitro will then be selected for 6 adjuvant intravesical instillations once weekly. Thereafter, patients are followed according to clinical guidelines by cystoscopy.
The aim of this trial is to use drug screens in PDO to precise treatment selection for adjuvant instillation therapies in patients with intermediate-risk NMIBC. The ultimate goal of this trial is to reduce the risk of cancer recurrence. In the future, we aim to conduct clinical multicenter trials with an increased sample size, a broader panel of compounds and a focus on the reduction of cancer recurrence by precision delivery of care. Trial registration NCT05024734.
在中危非肌肉浸润性膀胱癌（NMIBC）临床指南中建议进行辅助化疗药物灌注。然而，具体药物和方案尚未明确。在全球范围内，只有不到 15%的患者接受这种辅助化疗药物灌注。我们最近开发了一种用于 NMIBC 患者衍生类器官（PDO）生成的管道。在这项 II 期试验中，我们旨在使用我们的体外管道来选择最有效的药物用于 NMIBC 患者的化疗药物灌注。
招募首次诊断为中危 NMIBC 并需要行经尿道膀胱肿瘤切除术（TURBT）的患者。在 TURBT 期间，采集肿瘤样本，并将标本用于生成 PDO。一旦形成 PDO，就在它们上面进行表柔比星、丝裂霉素 C、吉西他滨和多西他赛的药物筛选。然后，选择体外抗肿瘤活性最高的药物进行 6 次每周一次的辅助膀胱内灌注。此后，根据临床指南通过膀胱镜对患者进行随访。
本试验旨在使用 PDO 中的药物筛选来精确选择中危 NMIBC 患者的辅助灌注治疗。该试验的最终目标是降低癌症复发的风险。未来，我们计划开展具有更大样本量、更广泛化合物组和关注通过精准护理降低癌症复发风险的多中心临床试验。试验注册 NCT05024734。
