Guidance of adjuvant instillation in intermediate-risk non-muscle invasive bladder cancer by drug screens in patient derived organoids: a single center, open-label, phase II trial.

Autor: Seiler R; Department of Urology, Hospital Center Biel, Spitalzentrum Biel, Vogelsang 84, 2501, Biel, Switzerland. r_seiler@gmx.ch.; Department for BioMedical Research, Translational Organoid Resource Core, University of Bern, Bern, Switzerland. r_seiler@gmx.ch., Egger M; Department of Urology, Hospital Center Biel, Spitalzentrum Biel, Vogelsang 84, 2501, Biel, Switzerland., De Menna M; Department for BioMedical Research, Translational Organoid Resource Core, University of Bern, Bern, Switzerland., Wehrli S; Department of Urology, Hospital Center Biel, Spitalzentrum Biel, Vogelsang 84, 2501, Biel, Switzerland., Minoli M; Department for BioMedical Research, Translational Organoid Resource Core, University of Bern, Bern, Switzerland., Radić M; Department for BioMedical Research, Translational Organoid Resource Core, University of Bern, Bern, Switzerland., Lyatoshinsky P; Department of Urology, Hospital Center Biel, Spitalzentrum Biel, Vogelsang 84, 2501, Biel, Switzerland.; Department of Urology, St. Gallen Cantonal Hospital, St. Gallen, Switzerland., Hösli R; Department of Pharmacy, Hospital Center Biel, Biel, Switzerland., Blarer J; Department of Urology, Hospital Center Biel, Spitalzentrum Biel, Vogelsang 84, 2501, Biel, Switzerland., Abt D; Department of Urology, Hospital Center Biel, Spitalzentrum Biel, Vogelsang 84, 2501, Biel, Switzerland., Kruithof-de Julio M; Department for BioMedical Research, Translational Organoid Resource Core, University of Bern, Bern, Switzerland.; Department for BioMedical Research, Urology Research Laboratory, University of Bern, 3008, Bern, Switzerland.; Department of Urology, Inselspital, Bern University Hospital, 3010, Bern, Switzerland.
Jazyk: angličtina
Zdroj: BMC urology [BMC Urol] 2023 May 11; Vol. 23 (1), pp. 89. Date of Electronic Publication: 2023 May 11.
DOI: 10.1186/s12894-023-01262-1
Abstrakt: Background: 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.
Methods: 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.
Discussion: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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