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

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.

Inclusion Criteria:

1. Patients with suspected prostate cancer and a PSA level ≥4.0 ng/mL
2. Patients who undergo PSMA PET imaging (including delayed phase imaging) prior to prostate biopsy
3. Patients who are willing to undergo prostate biopsy
4. Patients who provide written informed consent to participate in the study

Exclusion Criteria:

1. Patients who have received any prior prostate cancer-related treatment before the initial PSMA PET scan
2. Patients with a history of other malignancies within the past two years
3. 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.