Delayed PSMA PET/CT Imaging for Diagnosing Clinically Significant Prostate Cancer in Biopsy-Naïve Men With Suspected Prostate Cancer

Overview

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

Detailed description

Study Design and Objective This is a prospective, multicenter diagnostic accuracy study designed to evaluate whether delayed PSMA PET imaging improves diagnostic efficacy for clinically significant prostate cancer (csPCa) compared with standard imaging in patients with suspected newly diagnosed, treatment-naïve prostate cancer. Each patient serves as their own control.

Imaging Protocol

All enrolled patients undergo dual-time-point PSMA PET/CT before biopsy:

1. Standard acquisition: whole-body imaging at approximately 60 minutes post-injection. 2. Delayed acquisition: pelvic-focused imaging at 2-3 hours post-injection.

Reference Standard All patients undergo prostate biopsy using 12-core systematic biopsy plus targeted biopsy when indicated. Histopathology serves as the reference standard. csPCa is defined as ISUP grade group ≥2.

Primary Outcome To compare the area under the receiver operating characteristic curve (AUC) of delayed SUVmax versus standard SUVmax for detecting csPCa, and to determine whether delayed imaging is superior to standard imaging.

Secondary Outcomes

1. Optimal diagnostic thresholds for delayed SUVmax and ΔSUVmax, with internal validation; 2. Negative predictive value (NPV) and biopsy avoidance potential (especially in PI-RADS 4-5 patients); 3. Diagnostic performance in key subgroups (PI-RADS 2-3 vs. 4-5); 4. Proportion of patients with additional csPCa lesions detected only on delayed imaging; 5. Proportion of patients whose management would change after incorporating delayed results; 6. Exploratory subgroup analyses by PSA level, PSA density, and combined gray-zone subgroups.

Statistical Analysis The primary analysis will compare paired AUCs using the DeLong test . Secondary analyses will use appropriate paired tests with adjustment for multiple comparisons. Missing data will be handled by complete-case analysis.

Data Monitoring An independent data monitor reviews data integrity and protocol adherence. No interim analysis is planned. The study complies with the Declaration of Helsinki and local regulations.

Interventions

• Diagnostic test [⁶⁸Ga]Ga-PSMA PET/CT with Delayed Pelvic PET-Only Acquisition
  All 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 reco

Primary outcome measures

• Area Under the Curve (AUC) of Delayed SUVmax vs. Standard SUVmax for csPCa [Time frame: [Time Frame: Baseline (comparison of standard vs. delayed images)]]

Secondary outcome measures (9)

• Optimal Threshold of Delayed SUVmax for csPCa [Time frame: Baseline]
• Optimal Threshold of ΔSUVmax (Delayed Minus Standard) for csPCa [Time frame: Baseline]
• Diagnostic Performance of Optimal Thresholds in Validation Cohort [Time frame: Baseline]
• Negative Predictive Value for Biopsy Avoidance in PI-RADS 4-5 Patients [Time frame: Baseline]
• AUC of Delayed vs. Standard Imaging in PI-RADS 2-3 and PI-RADS 4-5 Subgroups [Time frame: Baseline]
• Proportion of Patients with Additional csPCa Lesions Detected Only on Delayed Imaging [Time frame: Baseline]
• Proportion of Patients with Change in Clinical Management After Delayed Imaging ( Exploratory) [Time frame: Baseline]
• Exploratory Subgroup Analyses by PSA and PSAD [Time frame: Baseline]
• Inter-Observer Agreement for SUVmax Measurement of the Most Suspicious Intraprostatic Lesion on Standard and Delayed PSMA PET/CT (Intraclass Correlation Coefficient, ICC, Exploratory) [Time frame: Baseline]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Case-crossover

Study locations

China · 9 centers

• The First Hospital of Lanzhou University — Lanzhou
• General Hospital of Ningxia Medical University — Yinchuan
• Qinghai University Affiliated Hospital — Xining
• Weinan Central Hospita — Weinan
• Xijing 986 Hospital — Xi'an
• Xijing Hospital — Xi'an
• Shaanxi Provincial People's Hospital — Xi'an
• The Second Affiliated Hospital of Shaanxi University of Chinese Medicine — Xianyang
• … and 1 more center

Identifiers

NCT: NCT07531329 · KY20262036-F-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗