Diagnostic Utility of rhPSMA-7.3 (18F) PET /CT Imaging in Patients With Prostate Cancer on Active Surveillance
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Proportion of participants with Grade Group ≥ 2
研究概览
简要总结
This investigator-initiated, prospective study evaluates the diagnostic utility of rhPSMA-7.3 (¹⁸F) PET/CT (flotufolastat F18, marketed as POSLUMA®) in men with biopsy-proven, low-risk or favorable intermediate-risk prostate cancer managed with active surveillance. The study aims to determine whether the addition of PSMA-based PET/CT to standard multiparametric MRI (mpMRI) improves detection of clinically significant prostate cancer compared to MRI alone. Eligible participants will undergo rhPSMA-7.3 (¹⁸F) PET/CT and mpMRI prior to confirmatory prostate biopsy. Biopsies will target areas identified on MRI, PET/CT, or both, and histopathologic outcomes will serve as the reference standard. The study will assess lesion-level concordance between PET/CT, MRI, and pathology, and evaluate the predictive value of PET/CT for disease upgrading. Approximately 120 participants will be enrolled at Mount Sinai Hospital over 12 months. Study participation will involve one imaging visit, one confirmatory biopsy, and follow-up through review of clinical results. There is minimal risk to participants beyond standard diagnostic procedures. The study is funded jointly by the Icahn School of Medicine at Mount Sinai and Blue Earth Diagnostics, which provides the imaging agent flotufolastat F18 and technical support.
详细描述
This investigator-initiated, single-center, prospective study aims to evaluate the diagnostic utility of rhPSMA-7.3 (¹⁸F) PET/CT (flotufolastat F18, marketed as POSLUMA®) in detecting clinically significant prostate cancer (csPCa) among men on active surveillance for low-risk or favorable intermediate-risk prostate cancer.
Background and Rationale: Active surveillance (AS) is the preferred management strategy for carefully selected men with low-risk and favorable intermediate-risk prostate cancer, balancing the avoidance of overtreatment against the need to identify disease progression early. Current surveillance strategies rely on serial PSA monitoring, digital rectal examination, mpMRI, and confirmatory biopsies. However, mpMRI can miss or underestimate clinically significant lesions, particularly those in the anterior or transitional zones. Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells and can be visualized using PET/CT imaging with radiolabeled PSMA ligands. The next-generation tracer rhPSMA-7.3 (¹⁸F), or flotufolastat F18, has demonstrated improved image resolution, favorable kinetics, and low urinary excretion compared to earlier PSMA ligands. Incorporating PSMA PET/CT into the active surveillance pathway may identify occult or higher-grade disease not detected by MRI, improving risk stratification and treatment decision-making.
Study Objectives: The primary objective of the study is to determine whether the addition of rhPSMA-7.3 (¹⁸F) PET/CT to standard mpMRI improves detection of clinically significant prostate cancer (ISUP Grade Group ≥2) in men on active surveillance.
Secondary objectives include: Comparing lesion-level concordance between PET/CT, mpMRI, and histopathology. Evaluating the predictive value of PET SUVmax for detecting clinically significant disease. Assessing diagnostic performance metrics (sensitivity, specificity, PPV, NPV) for PET/CT versus MRI. Quantifying the proportion of patients reclassified (i.e., upgraded or transitioned from AS to definitive treatment) based on PET/CT findings.
Exploratory endpoints include: Association between PET quantitative parameters (SUVmax, lesion volume) and PSA density. Characterization of PET-only lesions not visualized on MRI. Correlation of PET/CT findings with adverse pathological features (ECE, SVI, cribriform/intraductal carcinoma) at biopsy or surgery. Evaluation of lesion-level changes in SUVmax and volume in patients who undergo repeat PET/CT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
盲法说明
This is an open-label diagnostic imaging study. Neither participants nor investigators are blinded to the imaging procedures. However, imaging interpretation will be performed independently - PET/CT scans will be reviewed by nuclear medicine physicians blinded to MRI findings, and MRI scans will be reviewed by radiologists blinded to PET/CT results. Pathologists evaluating biopsy specimens will be blinded to imaging results to minimize interpretation bias.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male participants aged ≥18 years.
- •Histologically confirmed diagnosis of prostate adenocarcinoma.
- •Classified as low-risk or favorable intermediate-risk prostate cancer according to NCCN criteria: Low-risk: Grade Group 1, PSA <10 ng/mL, cT1-T2a Favorable intermediate-risk: Grade Group 2, PSA 10-20 ng/mL, cT2b-c Currently managed with active surveillance.
- •Able and willing to undergo rhPSMA-7.3 (¹⁸F) PET/CT imaging, mpMRI, and confirmatory prostate biopsy.
- •Able to provide written informed consent.
排除标准
- •A history of other active malignancy within the last 5 years, except for non-melanoma skin cancer.
- •Contraindication to 3-T mpMRI.
- •Significant intercurrent morbidity** limiting compliance with study protocols.
- •** Significant intercurrent morbidity refers to a substantial medical condition or complication that arises during a study or treatment, which is severe enough to impact the patient's participation, treatment outcomes, or overall prognosis. These conditions may be unrelated to the primary disease but can influence clinical decision-making, treatment efficacy, and patient safety. Examples include major infections, cardiovascular events, organ failure, or significant worsening of pre-existing comorbidities (https://doi.org/10.1016/S1053-4296(03)00031-6).
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to Agent(s) or other agents used in study.
研究组 & 干预措施
rhPSMA-7.3 (18F) PET/CT Imaging
Participants in this arm will undergo rhPSMA-7.3 (¹⁸F) PET/CT (flotufolastat F18, POSLUMA®) imaging and standard multiparametric MRI prior to confirmatory prostate biopsy. All participants receive the same imaging procedures; there are no control or comparison arms.
干预措施: rhPSMA-7.3 (18F) PET/CT Imaging (Flotufolastat F18, POSLUMA®) (Radiation)
rhPSMA-7.3 (18F) PET/CT Imaging
Participants in this arm will undergo rhPSMA-7.3 (¹⁸F) PET/CT (flotufolastat F18, POSLUMA®) imaging and standard multiparametric MRI prior to confirmatory prostate biopsy. All participants receive the same imaging procedures; there are no control or comparison arms.
干预措施: Flotufolastat F18 (Drug)
结局指标
主要结局
Proportion of participants with Grade Group ≥ 2
时间窗: Up to 3 months after PET/CT imaging
Detection rate measured by the proportion of participants with clinically significant prostate cancer (csPCa) (Grade Group ≥2) using rhPSMA-7.3 (¹⁸F) PET/CT compared to standard mpMRI confirmed on targeted or systematic biopsy Clinically significant prostate cancer is defined as Gleason Grade Group ≥ 2 (Gleason score ≥ 3+4 Predominantly well-formed glands with a lesser component of poorly-formed/fused/cribriform glands) based on histopathologic evaluation of biopsy cores obtained after PET/CT imaging.
次要结局
- Incremental detection rate of csPCa by PET/CT over MRI(up to 6 months)
- Lesion-level concordance between rhPSMA-7.3 (¹⁸F) PET/CT, multiparametric MRI, and histopathology(Up to 6 months following enrollment (from baseline imaging to confirmatory biopsy))
- Predictive value of PET SUVmax for detecting clinically significant disease(Baseline to 6 months)
- Sensitivity(Baseline to 6 months)
- Specificity(Baseline to 6 months)
- Positive Predictive Value (PPV)(Baseline to 6 months)
- Negative Predictive Value (NPV)(Baseline to 6 months)
- Number of participants that were reclassified(Baseline to 6 months)
研究者
Ashutosh Kumar Tewari
Professor and System Chair
Icahn School of Medicine at Mount Sinai