Brief Summary This prospective, multicenter study evaluates whether delayed PSMA PET imaging improves diagnostic efficacy for detecting clinically significant prostate cancer (Gleason score ≥7) compared with standard imaging in patients with suspected newly diagnosed prostate cancer. Each patient serves as their own control, with diagnostic performance compared between standard (60-minute) and delayed (2-3 hour) acquisitions.
Background PSMA PET has transformed prostate cancer imaging, with emerging evidence suggesting delayed acquisition may further improve diagnostic accuracy by increasing tumor-to-background ratio. Recent studies demonstrate that delayed imaging significantly reduces equivocal findings and enhances detection of clinically significant prostate cancer.
Need While standard PSMA PET is well-validated, prospective multicenter data specifically evaluating the incremental diagnostic value of delayed imaging for clinically significant prostate cancer in treatment-naïve patients are lacking. This study addresses this gap by systematically comparing standard and delayed imaging in a large, well-defined cohort.
Primary Outcome The primary outcome is to compare the area under the curve (AUC) of delayed SUVmax versus standard SUVmax for detecting clinically significant prostate cancer (csPCa), and to determine whether delayed imaging is superior to standard imaging.
Secondary Outcomes
1. Optimal diagnostic thresholds for delayed imaging
1. Determine the optimal threshold for delayed SUVmax using ROC analysis with the Youden index; 2. Determine the optimal threshold for ΔSUVmax (delayed minus standard SUVmax); 3. Validate the sensitivity, specificity, and AUC of these thresholds in an independent validation set. 2. Biopsy avoidance potential In patients with PI RADS 4-5 lesions, calculate the negative predictive value (NPV) using a predefined high threshold to estimate the proportion who could safely avoid biopsy. 3. Diagnostic performance in key subgroups Compare the AUC of delayed SUVmax versus standard SUVmax for csPCa detection in patients with PI RADS 2-3 and in those with PI RADS 4-5. 4. Additional lesion detection Proportion of patients with additional csPCa lesions detected only on delayed imaging, and the proportion whose PI RADS category would be upgraded based on these findings. 5. Clinical decision impact Proportion of patients in whom management recommendations would change after incorporating delayed imaging results, compared with standard imaging alone. 6. Exploratory subgroup analyses Stratify by PSA level (\<4, 4 10, \>10 ng/mL) and PSA density (\<0.10, 0.10-0.20, \>0.20 ng/mL/cc) to identify subgroups that derive the greatest benefit from delayed imaging; additionally, explore combined subgroups such as PI RADS 3 with PSA 4-10 or PSAD 0.10-0.20.
Inclusion Criteria
1. Suspected prostate cancer based on elevated PSA (≥4.0 ng/mL) or clinical symptoms 2. Undergo PSMA PET (standard + delayed) prior to prostate biopsy 3. Willing to undergo prostate biopsy 4. Provide written informed consent Exclusion Criteria
1\. Prior prostate cancer treatment before PSMA PET imaging 2. Other malignancy within past two years 3. Investigator-judged risk of serious complications interfering with study conduct
Patients with suspected prostate cancer and a PSA level ≥4.0 ng/mL
Patients who undergo PSMA PET imaging (including delayed phase imaging) prior to prostate biopsy
Patients who are willing to undergo prostate biopsy
Patients who provide written informed consent to participate in the study
Patients who have received any prior prostate cancer-related treatment before the initial PSMA PET scan
Patients with a history of other malignancies within the past two years
Patients judged by the study investigator to be at risk for serious complications that could interfere with the normal conduct of the study
The study population consists of a consecutive series of patients with suspected prostate cancer based on elevated PSA levels (≥4.0 ng/mL) who are referred for initial diagnostic evaluation at participating centers. All enrolled patients undergo dual-phase \[⁶⁸Ga\]Ga-PSMA-11 PET/CT imaging (standard whole-body acquisition at approximately 60 minutes post-injection, followed by delayed pelvic PET acquisition at approximately 2-3 hours post-injection) prior to transrectal or transperineal prostate biopsy. Eligible patients must have no prior history of prostate cancer-related treatment and no other active malignancy within the past two years. This prospective cohort represents a typical diagnostic population in whom the incremental value of delayed PSMA PET imaging for prostate cancer detection is being investigated.
Case-crossover
Prospective
[⁶⁸Ga]Ga-PSMA PET/CT with Delayed Pelvic PET-Only Acquisition
Diagnostic testAll enrolled patients undergo a dual-phase PSMA PET/CT imaging protocol consisting of: (1) a standard whole-body PET/CT acquisition performed at approximately 60 minutes after intravenous administration of \[⁶⁸Ga\]Ga-PSMA-11; and (2) a delayed pelvic PET acquisition performed at approximately 2-3 hours post-injection (exact timing to be standardized across participating centers based on local protocols and clinical workflow). The delayed phase does not include a separate CT scan; images are reconstructed using the CT dataset obtained from the initial whole-body acquisition for attenuation correction.
Area Under the Curve (AUC) of Delayed SUVmax vs. Standard SUVmax for csPCa
Compare the AUC of delayed SUVmax versus standard SUVmax for detecting clinically significant prostate cancer (ISUP grade group ≥2) using the DeLong test , to determine whether delayed imaging is superior.
Optimal Threshold of Delayed SUVmax for csPCa
Determine the optimal cutoff of delayed SUVmax for diagnosing clinically significant prostate cancer using ROC analysis with the Youden index.
Optimal Threshold of ΔSUVmax (Delayed Minus Standard) for csPCa
Calculate ΔSUVmax (delayed SUVmax minus standard SUVmax) and determine its optimal percentage-change cutoff for diagnosing clinically significant prostate cancer using ROC analysis with the Youden index.
Diagnostic Performance of Optimal Thresholds in Validation Cohort
Apply the derived thresholds to a temporally separate validation set to assess sensitivity, specificity, and AUC.
Negative Predictive Value for Biopsy Avoidance in PI-RADS 4-5 Patients
In patients with PI-RADS 4-5 lesions, calculate the negative predictive value using a predefined high threshold to estimate the proportion who could safely avoid biopsy.
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Xijing Hospital
Lead sponsor
Air Force Military Medical University, China
Collaborator
National Translational Science Center for Molecular Medicine
Collaborator
Shaanxi Provincial People's Hospital
Collaborator
Weinan Central Hospital
Collaborator
Yan'an University Affiliated Hospital
Collaborator
The Second Affiliated Hospital of Shaanxi University of Chinese Medicine
Collaborator
LanZhou University
Collaborator
Affiliated Hospital of Qinghai University
Collaborator
General Hospital of Ningxia Medical University
Collaborator
