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

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 Overview

• Status: Recruiting
• Conditions: Molecular Imaging; Suspected Prostate Cancer; Treatment-naive Prostate Cancer
• Intervention / Treatment: Diagnostic test: [⁶⁸Ga]Ga-PSMA PET/CT with Delayed Pelvic PET-Only Acquisition

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.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Jianhua Jiao, MD.; Phone Number: +86 18700919857; Email: 1531769428@qq.com

Study Locations

• China
  • Gansu
    • Lanzhou, Gansu, China
      • Recruiting
      • The First Hospital of Lanzhou University
      • Principal Investigator: Wei Zhang, MD.
      • Contact: Wei Zhang, MD.; Phone Number: +86 18700919857; Email: 1531769428@qq.com
  • Ningxia
    • Yinchuan, Ningxia, China
      • Recruiting
      • General Hospital of Ningxia Medical University
      • Principal Investigator: Zhiyong Lv, MD.
      • Contact: Zhiyong Lv; Phone Number: +86 18700919857; Email: 1531769428@qq.com
  • Qinghai
    • Xining, Qinghai, China
      • Recruiting
      • Qinghai University Affiliated Hospital
      • Contact: Guojun Chen, MD.; Phone Number: +86 18700919857; Email: 1531769428@qq.com
      • Principal Investigator: Guojun Chen, MD.
  • Shaanxi
    • Weinan, Shaanxi, China
      • Recruiting
      • Weinan Central Hospita
      • Contact: Weihong Zhao, MD.; Phone Number: +86 18700919857; Email: 1531769428@qq.com
      • Principal Investigator: Weihong Zhao, MD.
    • Xi'an, Shaanxi, China, 710032
      • Recruiting
      • Xijing Hospital
      • Contact: Jianhua Jiao, MD.; Phone Number: +86 18700919857; Email: 1531769428@qq.com
      • Principal Investigator: Weijun Qin, MD.
    • Xi'an, Shaanxi, China
      • Recruiting
      • Shaanxi Provincial People's Hospital
      • Contact: Yi Sun, MD.; Phone Number: +86 18700919857; Email: 1531769428@qq.com
      • Principal Investigator: Yi Sun, MD.
    • Xi'an, Shaanxi, China, 710032
      • Recruiting
      • Xijing 986 Hospital
      • Principal Investigator: Wuhe Zhang, MD.
      • Contact: Wuhe Zhang; Phone Number: +86 18700919857; Email: 1531769428@qq.com
    • Xianyang, Shaanxi, China
      • Recruiting
      • The Second Affiliated Hospital of Shaanxi University of Chinese Medicine
      • Contact: Wei Zheng, MD.; Phone Number: +86 18700919857; Email: 1531769428@qq.com
      • Principal Investigator: Wei Zheng, MD.
    • Yan’an, Shaanxi, China
      • Recruiting
      • Affiliated Hospital of Yan'an University
      • Contact: Jixue Gao, MD.; Phone Number: +86 18700919857; Email: 1531769428@qq.com
      • Principal Investigator: Jixue Gao, MD.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Study Cohort; All enrolled patients with suspected prostate cancer undergo both standard and delayed PSMA PET imaging. Each patient serves as their own control, with diagnostic performance compared between the standard imaging phase and the delayed imaging phase.

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 reconstructed using the CT dataset obtained from the initial whole-body acquisition for attenuation correction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	[Time Frame: Baseline (comparison of standard vs. delayed images)]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline
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.	Baseline
Diagnostic Performance of Optimal Thresholds in Validation Cohort	Apply the derived thresholds to a temporally separate validation set to assess sensitivity, specificity, and AUC.	Baseline
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.	Baseline
AUC of Delayed vs. Standard Imaging in PI-RADS 2-3 and PI-RADS 4-5 Subgroups	Compare the AUC of delayed Imaging versus standard SUVmax for csPCa detection separately in patients with PI-RADS 2-3 (target of PRIMARY2 study) and PI-RADS 4-5.	Baseline
Proportion of Patients with Additional csPCa Lesions Detected Only on Delayed Imaging	Calculate the proportion of patients who have additional csPCa lesions identified exclusively on delayed images that were not seen on standard images.	Baseline
Proportion of Patients with Change in Clinical Management After Delayed Imaging ( Exploratory)	Proportion of patients for whom management recommendations (biopsy vs. surveillance) would change after incorporating delayed imaging results, compared with standard imaging alone.	Baseline
Exploratory Subgroup Analyses by PSA and PSAD	Compare AUC of delayed vs. standard SUVmax for csPCa detection stratified by PSA level (<4, 4-10, >10 ng/mL) and PSA density (<0.10, 0.10-0.20, >0.20 ng/mL/cc); additionally explore combined gray-zone subgroups (e.g., PI-RADS 3 with PSA 4-10 or PSAD 0.10-0.20).	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)	Two nuclear medicine physicians independently identify the most suspicious intraprostatic lesion on both standard and delayed images and measure its maximum standardized uptake value (SUVmax) once per lesion. Inter-observer agreement for SUVmax measurement will be assessed using the intraclass correlation coefficient (ICC, two-way random model, absolute agreement). ICC values with 95% confidence intervals will be reported separately for standard and delayed imaging. Higher ICC indicates better measurement consistency.	Baseline

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Collaborators: LanZhou University; Shaanxi Provincial People's Hospital; Air Force Military Medical University, China; General Hospital of Ningxia Medical University; Affiliated Hospital of Qinghai University; Weinan Central Hospital; Yan'an University Affiliated Hospital; The Second Affiliated Hospital of Shaanxi University of Chinese Medicine; National Translational Science Center for Molecular Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2021
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): March 5, 2028

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: April 8, 2026
• First Posted (Actual): April 15, 2026

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Efficacy; Prostate Cancer; Diagnostic; PSMA PET; Delayed imaging
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Pathological Conditions, Signs and Symptoms; Prostatic Neoplasms; Disease
• Other Study ID Numbers: KY20262036-F-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No