Real-time Fluorescence Microscopy for Intraoperative Assessment of Prostate Biopsy Cores (FLASH) (FLASH)
Fluorescence Microscope for Localized Assessment and Sparing of Histology in Prostate Cancer (FLASH): An International, Multicentre, Prospective Diagnostic Accuracy and Clinical Utility Study With Blinded Index-Test and Reference-Standard Readers
Current prostate cancer diagnosis relies on MRI-targeted biopsy combined with a 12-core systematic biopsy. The systematic component is a major driver of overdiagnosis of insignificant cancer and biopsy-related morbidity, and conventional pathology takes 1-2 weeks, causing significant patient anxiety. The EndoScell system is a handheld, real-time fluorescence microscope that can display the microscopic structure of a fresh biopsy core within minutes, without damaging the tissue.
In this study, every biopsy core from men undergoing standard combined (targeted plus systematic) prostate biopsy will be scanned with this device immediately after removal, and the result will be compared with the final conventional pathology report of the very same core. The device result will not be used to guide any patient care. The study will measure how accurate the device is and simulate how many systematic biopsies could safely be avoided in the future if a positive device reading were used to stop further sampling.
Descripción general del estudio
Estado
Descripción detallada
FLASH is an investigator-initiated, international, multicentre, prospective diagnostic-accuracy and clinical-utility study with a within-patient paired design, conducted and reported in accordance with STARD 2015. Biopsy-naïve men with suspected prostate cancer (serum PSA >4 ng/mL and/or abnormal digital rectal examination) and at least one MRI-visible lesion (PI-RADS v2.1 score 3-5) will undergo standard-of-care combined targeted and systematic prostate biopsy.
Immediately after extraction, every core will undergo ex vivo dual staining (fluorescein sodium for 30 seconds followed by methylene blue for 30 seconds) and contact-mode scanning with the EndoScell real-time fluorescence microscope (model MES-1000P), completed within 5 minutes per core by certified technicians. Each core is assigned to a three-tier category (0 = negative/suspected low-grade; 1 = suspected clinically significant prostate cancer; 2 = equivocal). The interval from core extraction to formalin fixation will not exceed 15 minutes. All cores then undergo routine formalin-fixed paraffin-embedded (FFPE) histopathology with haematoxylin and eosin staining, with immunohistochemistry as clinically indicated, reported by senior uropathologists.
Bidirectional blinding is enforced throughout: technicians are blinded to all clinical data, MRI findings, and core origin; device results are withheld from the treating team and never enter the medical record; uropathologists are blinded to all device data; the statistician works with coded variables until database lock. Central pathology review is performed for discordant and equivocal cases.
The primary outcome is patient-level diagnostic accuracy (sensitivity, specificity, positive and negative predictive values with exact 95% confidence intervals) of the device for clinically significant prostate cancer (ISUP grade group >=2) against FFPE histopathology in the intention-to-diagnose population. Secondary outcomes include core-level concordance with cluster adjustment, inter-reader reproducibility, tissue-integrity assessment, operational metrics, and a prespecified decision-analytic simulation of a "Positive-then-Stop" biopsy-sparing pathway, which is hypothesis-generating and does not alter patient care. The accuracy and utility estimates are intended to inform the design of a future randomised de-implementation trial.
Tipo de estudio
Inscripción (Estimado)
Contactos y Ubicaciones
Estudio Contacto
- Nombre: biming He
- Número de teléfono: 15502139410
- Correo electrónico: 190589109@qq.com
Copia de seguridad de contactos de estudio
- Nombre: haifeng wang
- Número de teléfono: 86-13681750891
- Correo electrónico: 190589109@qq.com
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Método de muestreo
Población de estudio
patients who suspected to have prostate cancer
Descripción
Inclusion Criteria:
- Age >= 40 years;
- Serum total PSA > 4.0 ng/mL and/or abnormal digital rectal examination;
- Biopsy-naïve;
- Pre-biopsy 3.0-T multiparametric MRI demonstrating at least one suspicious lesion (PI-RADS v2.1 score 3-5);
- Fit for transperineal or transrectal prostate biopsy under local, regional, or general anaesthesia;
- Written informed consent.
Exclusion Criteria:
- Prior treatment for prostate cancer (surgery, radiotherapy, focal therapy, or androgen-deprivation therapy), or use of 5-alpha-reductase inhibitors within the preceding 6 months;
- Acute prostatitis or active urinary tract infection;
- Contraindications to MRI (e.g., incompatible implants, severe claustrophobia);
- Severe coagulation disorders or uncorrectable bleeding tendency;
- History of major anorectal surgery precluding safe insertion of the endorectal ultrasound probe (where transrectal guidance is used);
- Any other condition that, in the investigator's judgement, makes the participant unsuitable for the trial.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Modelos observacionales: COHORT
- Perspectivas temporales: PROSPECTIVE
Cohortes e Intervenciones
Grupo / Cohorte |
Intervención / Tratamiento |
|---|---|
|
Biopsy-naïve men with suspected prostate cancer
Men undergoing standard-of-care combined targeted plus systematic prostate biopsy; every core undergoes ex vivo EndoScell fluorescence microscopy (index test) followed by FFPE histopathology (reference standard). Device results are not used for patient care. |
Fresh biopsy cores are stained with fluorescein sodium (30 s) and methylene blue (30 s), scanned in contact mode within 5 minutes per core, and categorised on a three-tier scale; the tissue then proceeds to routine FFPE histopathology unchanged. The test is performed on excised tissue only and does not influence clinical management. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Patient-level sensitivity of the EndoScell system for clinically significant prostate cancer
Periodo de tiempo: Index test on Day 0; reference standard completed Day 7-14
|
Proportion of reference-positive participants (any core with ISUP grade group >=2 on FFPE histopathology) with at least one core read as Category 1 (suspected clinically significant prostate cancer) on the index test; reported with exact (Clopper-Pearson) 95% confidence interval in the intention-to-diagnose population. |
Index test on Day 0; reference standard completed Day 7-14
|
|
Patient-level negative predictive value (NPV) of the EndoScell system
Periodo de tiempo: Index test on Day 0; reference standard completed Day 7-14
|
Proportion of participants with no Category 1 core who are reference-negative; exact 95% CI. |
Index test on Day 0; reference standard completed Day 7-14
|
|
Patient-level positive predictive value (PPV) of the EndoScell system
Periodo de tiempo: Index test on Day 0; reference standard completed Day 7-14
|
Proportion of participants with at least one Category 1 core who are reference-positive (ISUP grade group >=2 on FFPE); exact 95% CI. |
Index test on Day 0; reference standard completed Day 7-14
|
|
Patient-level specificity of the EndoScell system for clinically significant prostate cancer
Periodo de tiempo: Index test on Day 0; reference standard completed Day 7-14
|
Proportion of reference-negative participants with no core read as Category 1; equivocal (Category 2) readings are grouped with test-negative in the primary analysis, with worst-case/best-case/exclusion sensitivity analyses prespecified; exact 95% CI. |
Index test on Day 0; reference standard completed Day 7-14
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Core-level diagnostic concordance
Periodo de tiempo: Index test on Day 0; reference standard completed Day 7-14
|
Per-core sensitivity, specificity, PPV and NPV of the index test against FFPE histopathology, overall and stratified by core origin (targeted vs systematic), with cluster-robust 95% CIs from a generalised estimating equation (logit link, exchangeable correlation) accounting for within-patient clustering. |
Index test on Day 0; reference standard completed Day 7-14
|
|
Biopsy-sparing rate of the simulated "Positive-then-Stop" pathway
Periodo de tiempo: Simulation performed after database lock (estimated December 2028)
|
Proportion of participants in whom systematic biopsy would have been omitted (any targeted core read as Category 1), and the corresponding proportion of systematic cores avoided; prespecified deterministic simulation, exact 95% CIs. Hypothesis-generating; does not alter patient care. |
Simulation performed after database lock (estimated December 2028)
|
|
Overdiagnosis reduction in the simulated pathway
Periodo de tiempo: Simulation performed after database lock (estimated December 2028)
|
Number and proportion of ISUP grade group 1 diagnoses that would have been averted by omitting systematic biopsy after a positive intraoperative reading; exact 95% CI. |
Simulation performed after database lock (estimated December 2028)
|
|
Clinically significant prostate cancer miss rate in the simulated pathway
Periodo de tiempo: Simulation performed after database lock (estimated December 2028)
|
Number and proportion of reference-positive participants who would have been missed under the simulated pathway (targeted cores negative on both index test and FFPE, with csPCa found only in systematic cores); exact 95% CI. |
Simulation performed after database lock (estimated December 2028)
|
|
Net benefit of the simulated pathway (decision-curve analysis)
Periodo de tiempo: Simulation performed after database lock (estimated December 2028)
|
Decision-curve analysis with patient-level bootstrap (1000 resamples) comparing three strategies (combined biopsy for all; targeted biopsy alone; Positive-then-Stop) across threshold probabilities. |
Simulation performed after database lock (estimated December 2028)
|
|
Inter-reader agreement of index-test readings
Periodo de tiempo: Video re-reading after completion of enrolment (estimated 2028)
|
Cohen's kappa (three-tier scale and dichotomised Category 1 vs 0/2) and percent agreement between two blinded technicians re-interpreting a random 20% subset of archived scan videos (~900-1200 cores). |
Video re-reading after completion of enrolment (estimated 2028)
|
|
Tissue-integrity (tissue-compromise) rate
Periodo de tiempo: Day 7-14 (pathology reporting)
|
Proportion of cores flagged by uropathologists as degraded, unreadable, or inadequate for definitive H&E/IHC evaluation attributable to the staining/scanning procedure; one-sided upper 95% confidence bound compared against the 1% acceptability benchmark. |
Day 7-14 (pathology reporting)
|
|
Operational performance of the index test
Periodo de tiempo: Day 0
|
Per-core scanning time, extraction-to-fixation interval, equivocal (Category 2) rate, and device/scan failure rate, summarised descriptively by centre and calendar quarter. |
Day 0
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Silla de estudio: haifeng wang, Changhai Hospital
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades urogenitales
- Enfermedades Genitales
- Procesos Patológicos
- Neoplasias Genitales Masculinas
- Neoplasias urogenitales
- Neoplasias por sitio
- Neoplasias
- Enfermedades Genitales Masculinas
- Enfermedades prostáticas
- Enfermedades urogenitales masculinas
- Condiciones Patológicas, Signos y Síntomas
- Neoplasias prostáticas
- Enfermedad
Otros números de identificación del estudio
- 2026304
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
De-identified participant-level data and the signed statistical analysis plan will be made available on reasonable request to the corresponding author, subject to a methodologically sound proposal and a signed data-access agreement.
Marco de tiempo para compartir IPD
Beginning 12 months after publication of the primary results, for a period of 5 years.
Criterios de acceso compartido de IPD
Proposals will be reviewed by the Trial Steering Committee; access requires approval and a data-access agreement.
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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