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.
Přehled studie
Postavení
Detailní popis
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.
Typ studie
Zápis (Odhadovaný)
Kontakty a umístění
Studijní kontakt
- Jméno: biming He
- Telefonní číslo: 15502139410
- E-mail: 190589109@qq.com
Studijní záloha kontaktů
- Jméno: haifeng wang
- Telefonní číslo: 86-13681750891
- E-mail: 190589109@qq.com
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Metoda odběru vzorků
Studijní populace
patients who suspected to have prostate cancer
Popis
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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Observační modely: COHORT
- Časové perspektivy: PROSPECTIVE
Kohorty a intervence
Skupina / kohorta |
Intervence / Léčba |
|---|---|
|
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. |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Patient-level sensitivity of the EndoScell system for clinically significant prostate cancer
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Core-level diagnostic concordance
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
|
Spolupracovníci a vyšetřovatelé
Sponzor
Vyšetřovatelé
- Studijní židle: haifeng wang, Changhai Hospital
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- 2026304
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu 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.
Časový rámec sdílení IPD
Beginning 12 months after publication of the primary results, for a period of 5 years.
Kritéria přístupu pro sdílení IPD
Proposals will be reviewed by the Trial Steering Committee; access requires approval and a data-access agreement.
Typ podpůrných informací pro sdílení IPD
- PROTOKOL STUDY
- MÍZA
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