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.

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  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 100968571 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2490 (Electronic) Linking ISSN: 14712490 NLM ISO Abbreviation: BMC Urol Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : BioMed Central, [2001-
    • Subject Terms:
      Non-Muscle Invasive Bladder Neoplasms* ; Urinary Bladder Neoplasms*/surgery; Humans ; Neoplasm Recurrence, Local/pathology ; Mitomycin/therapeutic use ; Adjuvants, Immunologic/therapeutic use ; Administration, Intravesical ; Neoplasm Invasiveness
    • Abstract:
      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).)
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    • Grant Information:
      310030_184933 Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
    • Contributed Indexing:
      Keywords: Adjuvant instillation therapy; Non-muscle invasive bladder cancer; Patient derived organoids; Precision oncology
    • Molecular Sequence:
      ClinicalTrials.gov NCT05024734
    • Accession Number:
      50SG953SK6 (Mitomycin)
      0 (Adjuvants, Immunologic)
    • Publication Date:
      Date Created: 20230511 Date Completed: 20230515 Latest Revision: 20230515
    • Publication Date:
      20240829
    • Accession Number:
      PMC10176900
    • Accession Number:
      10.1186/s12894-023-01262-1
    • Accession Number:
      37170307