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.
調査の概要
状態
条件
詳細な説明
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.
研究の種類
入学 (推定)
連絡先と場所
研究連絡先
- 名前：biming He
- 電話番号：15502139410
- メール：190589109@qq.com
研究連絡先のバックアップ
- 名前：haifeng wang
- 電話番号：86-13681750891
- メール：190589109@qq.com
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
patients who suspected to have prostate cancer
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 観測モデル：COHORT
- 時間の展望：PROSPECTIVE
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
|
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. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Patient-level sensitivity of the EndoScell system for clinically significant prostate cancer
時間枠：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
時間枠：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
時間枠：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
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Core-level diagnostic concordance
時間枠：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
時間枠：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
時間枠：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
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
|
協力者と研究者
スポンサー
捜査官
- スタディチェア：haifeng wang、Changhai Hospital
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 2026304
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
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.
IPD 共有時間枠
Beginning 12 months after publication of the primary results, for a period of 5 years.
IPD 共有アクセス基準
Proposals will be reviewed by the Trial Steering Committee; access requires approval and a data-access agreement.
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
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米国FDA規制医薬品の研究
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