Serial PSMA PET for Treatment Response Monitoring in Newly Diagnosed Clinically Significant, Treatment-Naïve Prostate Cancer - A Prospective, Multicenter Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 110
- 试验地点
- 9
- 主要终点
- Absolute and relative change in SUVmax from baseline to follow-up PSMA PET
研究概览
简要总结
This prospective, multicenter study aims to evaluate the clinical utility of serial PSMA PET for therapy monitoring in patients with newly diagnosed clinically significant prostate cancer.
Clinically significant prostate cancer is defined as Gleason score ≥7.Patients will undergo baseline PSMA PET/CT prior to any treatment. A second PSMA PET/CT will be performed either at PSA recurrence (PSA rise ≥2 ng/mL above nadir after radiotherapy or biochemical progression per PCWG3 criteria) or at a fixed time window of 12-24 months after treatment completion for those without biochemical recurrence.
Primary Outcome:
1. Absolute and relative change in SUVmax from baseline to follow-up PSMA PET, correlated with treatment response categories (complete response, partial response, stable disease, progressive disease) defined by a composite reference standard (PSA kinetics, conventional imaging, clinical outcomes).
[Time Frame: Baseline and follow-up (up to 24 months)]
Secondary Outcomes:
- Absolute and relative change in the number of PSMA-avid lesions (primary tumor, nodal, bone metastases) as a supportive exploratory endpoint.
- Proportion of patients with treatment strategy change following serial PSMA PET.
- Agreement between PSMA PET response (≥30% decrease in SUVmax) and PSA50 response (≥50% PSA decline) using Cohen's kappa.
- Agreement between PSMA PET response and PSA90 response (≥90% PSA decline).
- Prognostic value of baseline and follow-up PSMA PET parameters for progression-free survival (PFS).
- Prognostic value of baseline and follow-up PSMA PET parameters for time to castration resistance (ADT-treated patients only).
- Subgroup analyses by treatment type (radiotherapy, ADT, chemotherapy), baseline disease burden (oligometastatic vs. polymetastatic), and Gleason grade group (≤7 vs. ≥8).
- Inter-reader agreement for PSMA-avid lesion counts. [Time Frame: Up to 2 years, except inter-reader agreement at baseline]
Need:
Current treatment response evaluation relies on PSA changes and conventional imaging, which lack sensitivity and accuracy for early assessment. PSMA PET has demonstrated superior sensitivity for detecting prostate cancer lesions, but its role in longitudinal therapy monitoring remains undefined, with no specific regulatory approval for this indication. Prospective data on serial PSMA PET to guide treatment decisions in patients with clinically significant prostate cancer (Gleason score ≥7) are urgently needed.
Inclusion Criteria:
- Newly diagnosed, histologically confirmed clinically significant prostate cancer with Gleason score ≥7.
- Planned curative-intent or systemic therapy.
- Baseline PSMA PET performed prior to any treatment.
- Age ≥18 years.
- Written informed consent.
Exclusion Criteria:
- Prior prostate cancer treatment before baseline PSMA PET.
- Contraindication to PSMA PET imaging.
- Other active malignancy within past two years (excluding non-melanoma skin cancer).
- Unable to comply with follow-up schedule.
详细描述
Background and Rationale Prostate cancer is the fastest-growing male malignancy in China, with an average annual increase of approximately 12.6% over the past decade. The concept of clinically significant prostate cancer (csPCa) distinguishes patients who require active treatment from those with indolent disease. For this study, csPCa is defined as Gleason score ≥7 (grade group ≥2).
PSMA PET has emerged as the most sensitive imaging modality for detecting prostate cancer lesions, outperforming conventional imaging (CT, bone scan). However, its application has been primarily limited to single time-point assessments for initial staging or biochemical recurrence. Standardized response criteria such as RECIP 1.0 (Response Evaluation Criteria in PSMA PET/CT) and PPP (PSMA PET Progression) criteria have been validated in the context of radiopharmaceutical therapy and show robust prognostic value (HR for mortality 3.48; 95% CI: 2.64-4.59) , but their role in patients treated with androgen signaling inhibitors is less clear due to potential "PSMA flare" or treatment-induced heterogeneous expression. Prospective data on serial PSMA PET for therapy monitoring in csPCa are urgently needed.
Study Design and Technical Phases This is a prospective, multicenter, observational cohort study. Eligible patients are newly diagnosed csPCa with Gleason score ≥7, scheduled for curative-intent or systemic therapy (radiotherapy, ADT, chemotherapy, or combination).
PSMA PET Acquisition Protocol
Baseline scan: Performed prior to any treatment. Radiotracer: 68Ga-PSMA-11 or 18F-DCFPyL, dose according to institutional guidelines, acquisition starting 60 minutes post-injection.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Newly diagnosed, histologically confirmed prostate cancer with Gleason score ≥7 (clinically significant prostate cancer).
- •Planned to receive curative-intent therapy (radical prostatectomy or radiotherapy) or systemic therapy (androgen deprivation therapy, chemotherapy, or combination).
- •Undergo baseline PSMA PET/CT imaging prior to any prostate cancer-related treatment.
- •Age ≥18 years.
- •Willing and able to comply with the follow-up schedule, including the second PSMA PET/CT scan.
- •Provide written informed consent.
排除标准
- •Any prior prostate cancer treatment (including hormonal therapy, radiotherapy, chemotherapy, or surgery) before baseline PSMA PET/CT.
- •Contraindications to PSMA PET/CT imaging (e.g., known severe allergic reaction to radiotracer components, inability to lie flat for the duration of the scan).
- •Other active malignancy within the past two years, excluding non-melanoma skin cancer.
- •Severe comorbidities or conditions that, in the opinion of the investigator, could interfere with study compliance or pose a significant risk to the patient.
- •Unable or unwilling to provide informed consent.
研究组 & 干预措施
Clinically Significant Prostate Cancer Cohort
A single cohort of 110 patients with newly diagnosed, treatment-naïve clinically significant prostate cancer (defined as Gleason score ≥7). All patients undergo baseline PSMA PET imaging prior to any treatment, followed by a second PSMA PET scan triggered by PSA recurrence (PSA ≥0.2 ng/mL after radical prostatectomy or ≥2 ng/mL above nadir after radiotherapy) or performed at 12-24 months after treatment completion if no recurrence occurs. Patients receive standard clinical treatments (radiotherapy, radical prostatectomy, ADT, or chemotherapy) as determined by their physicians. The cohort is used to evaluate the utility of serial PSMA PET for treatment response monitoring and its association with clinical outcomes.
结局指标
主要结局
Absolute and relative change in SUVmax from baseline to follow-up PSMA PET
时间窗: Baseline and follow-up (12-24 months post-treatment or at time of PSA recurrence); overall assessment up to 2 years.
Description: SUVmax (maximum standardized uptake value) will be measured in the most intense PSMA-avid lesion (up to 5 lesions recorded; the highest value used). Absolute change (ΔSUVmax) and relative change (percentage) will be calculated. The correlation with treatment response categories (complete response, partial response, stable disease, progressive disease) defined by a composite reference standard (PSA kinetics, conventional imaging, clinical outcomes) will be assessed using Spearman correlation and linear mixed-effects models. Measurement tool and unit: PSMA PET/CT; unitless (SUVmax) and percentage (%).
次要结局
- Proportion of patients with treatment strategy change following serial PSMA PET(Up to 2 years)
- Absolute and relative change in number of PSMA-avid lesions (supportive endpoint)(Baseline and follow-up (12-24 months or at PSA recurrence); overall up to 2 years.)
- Agreement between PSMA PET response and PSA50 response(Up to 2 years)
- Agreement between PSMA PET response and PSA90 response(Up to 2 years)
- Association of PSMA PET parameters with progression-free survival (PFS)(exploratory)(Up to 2 years)
- Association of baseline and follow-up PSMA PET parameters with time to castration resistance (exploratory, ADT patients only)(Up to 2 years)
- Subgroup analyses of PSMA PET parameter changes (exploratory)(Up to 2 years)
- Inter-reader agreement for PSMA-avid lesion counts (exploratory)(Baseline)