First-in-human outpatient management of recurrent NMIBC with the Multi4 instrument

To evaluate the feasibility, safety and diagnostic performance of outpatient management of recurrent non-muscle-invasive bladder cancer (NMIBC) under local anaesthesia using the Multi4 instrument, a series of preclinical studies were performed followed by a first-in-human clinical investigation. NMIBC is associated with frequent recurrence, requiring repeated transurethral resection of the bladder (TUR-B) under anaesthesia, resulting in substantial healthcare burden. The Multi4 instrument integrates local anaesthesia injection, diathermy biopsy, coagulation and automated tissue retrieval. The primary objective was to determine whether Multi4 provides histologically evaluable biopsies in an outpatient setting, and secondary objectives included safety, usability, patient-reported outcomes and health-economic impact.

Preclinical in vivo evaluation was performed in 13 pigs to assess safety, biopsy quality, coagulation efficacy and perforation risk. A prospective, open-label, single-arm clinical investigation enrolled 18 adults with recurrent Ta/T1 NMIBC (≤10 mm lesions). Procedures were performed under local anaesthesia using flexible cystoscopy. The primary endpoint was the proportion of evaluable biopsies. Secondary endpoints included adverse events, usability, pain (0-10 scale), EQ-5D and cost comparison versus standard TUR-B. Diagnostic yield was also assessed at the patient level.

A total of 550 porcine biopsies demonstrated immediate haemostasis and preserved tissue architecture suitable for histological assessment. Perforation occurred after 7-11 sequential biopsies at the same location, indicating a wide safety margin. Clinically, 134/145 biopsies (92%) were evaluable and the primary endpoint was met. Diagnostic yield per patient was 89%. No device-related adverse events or Clavien-Dindo complications occurred. All procedures were completed under local anaesthesia without conversion to standard TUR-B or use of additional instruments. The median pain score was 0.5/10. Estimated per-procedure cost reduction was 73-89% versus TUR-B.

Multi4 enables feasible and safe outpatient biopsy and lesion management of small recurrent NMIBC under local anaesthesia with substantially reduced resource use while maintaining diagnostic reliability.