Serial PSMA PET for Therapy Monitoring in Clinically Significant Prostate Cancer (PSMA-TM)

Serial PSMA PET for Treatment Response Monitoring in Newly Diagnosed Clinically Significant, Treatment-Naïve Prostate Cancer - A Prospective, Multicenter Study

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:

1. Absolute and relative change in the number of PSMA-avid lesions (primary tumor, nodal, bone metastases) as a supportive exploratory endpoint.
2. Proportion of patients with treatment strategy change following serial PSMA PET.
3. Agreement between PSMA PET response (≥30% decrease in SUVmax) and PSA50 response (≥50% PSA decline) using Cohen's kappa.
4. Agreement between PSMA PET response and PSA90 response (≥90% PSA decline).
5. Prognostic value of baseline and follow-up PSMA PET parameters for progression-free survival (PFS).
6. Prognostic value of baseline and follow-up PSMA PET parameters for time to castration resistance (ADT-treated patients only).
7. Subgroup analyses by treatment type (radiotherapy, ADT, chemotherapy), baseline disease burden (oligometastatic vs. polymetastatic), and Gleason grade group (≤7 vs. ≥8).
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:

1. Newly diagnosed, histologically confirmed clinically significant prostate cancer with Gleason score ≥7.
2. Planned curative-intent or systemic therapy.
3. Baseline PSMA PET performed prior to any treatment.
4. Age ≥18 years.
5. Written informed consent.

Exclusion Criteria:

1. Prior prostate cancer treatment before baseline PSMA PET.
2. Contraindication to PSMA PET imaging.
3. Other active malignancy within past two years (excluding non-melanoma skin cancer).
4. Unable to comply with follow-up schedule.

Study Overview

• Status: Recruiting
• Conditions: High-risk Prostate Cancer; PSMA PET; Treatment Response; Therapy Monitoring

Detailed Description

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.

Follow-up scan: Triggered either by:

PSA recurrence: PSA rise ≥2 ng/mL above nadir after radiotherapy, or biochemical progression per PCWG3 criteria; OR

Fixed time window: 12-24 months after treatment completion (for patients without biochemical recurrence).

Consistency: Same radiotracer and scanner type will be used whenever possible. Images centrally collected and analyzed.

Quantitative PSMA PET Parameters (Primary)

SUVmax change: Maximum standardized uptake value measured in the most intense PSMA-avid lesion. Up to five lesions per patient may be recorded; the highest SUVmax is used for analysis. Absolute and relative (percentage) change from baseline to follow-up will be calculated.

PSMA-avid lesion count change: Total number of PSMA-avid lesions per patient, including primary tumor, nodal metastases, and bone metastases. Counting rules:

Primary tumor: counted as 1 lesion if present and PSMA-avid.

Lymph nodes: each distinct node with SUVmax > liver background and typical morphology counted separately; contiguous nodal clusters counted as 1.

Bone metastases: each discrete focus counted separately; diffuse marrow involvement counted as 1 "marrow" lesion.

Excluded: sites of physiological uptake (e.g., salivary glands, bowel, renal collecting system).

Two independent nuclear medicine physicians will perform counts; discrepancies resolved by consensus.

Composite Reference Standard for Treatment Response

Treatment response (ground truth) will be categorized as: complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) based on an adjudicated composite reference standard:

PSA kinetics: PSA50, PSA90, PSA nadir, time to PSA progression per PCWG3.

Conventional imaging: CT and bone scan, assessed per RECIST 1.1 (for soft tissue) and PCWG3 (for bone) by two independent radiologists blinded to PSMA PET results; disagreements resolved by a third reader.

Clinical outcomes: Need for treatment switch, occurrence of symptomatic progression, or death.

The composite standard will be determined by a clinical adjudication committee blinded to PSMA PET results.

Statistical Considerations (Detailed) Sample Size Justification

Target enrollment: 110 patients (allowing 10% loss to follow-up, aiming for 100 evaluable). Assumptions based on csPCa (Gleason ≥7) population:

Prognostic analysis: Expected 2-year progression rate 30% → ~30 events. With 100 patients, 80% power to detect a hazard ratio of 2.0 between PSMA PET-defined responders and non-responders (two-sided alpha 0.05, log-rank test). This detectable HR is consistent with prior RECIP 1.0 validation studies (HR 3.2).

Concordance analysis: For Cohen's kappa, 100 patients yield a 95% CI half-width of ±0.10 when kappa ≈ 0.70, sufficient for agreement assessment.

Subgroup analyses: Descriptive only; no formal power calculation.

Statistical Analysis Plan

All analyses will be performed using R (version ≥4.2). The final SAP will be finalized before database lock.

Primary analysis:

Linear mixed-effects models (LMM) for log-transformed SUVmax and lesion count, with fixed effects for time point (baseline, follow-up), treatment type, and random intercept per patient.

Multinomial logistic regression to assess association between ΔSUVmax/Δlesion count and the composite reference standard response categories, adjusting for baseline disease volume.

Survival analysis:

Progression-free survival (PFS): time from treatment initiation to radiographic progression (per composite standard), PSA progression (PCWG3), or death.

Time to castration resistance (for ADT patients).

Kaplan-Meier curves and log-rank tests comparing PFS between PSMA PET response groups (e.g., responders vs. non-responders, defined by ≥30% decrease in SUVmax or lesion count).

Cox proportional hazards models for baseline and follow-up parameters, adjusting for clinical covariates (PSA, Gleason, T stage, treatment type).

Agreement analysis:

Cohen's kappa with quadratic weights for agreement between PSMA PET response categories (binary or ordinal) and PSA response categories (PSA50, PSA90, PSA progression). Percent agreement and 95% CI reported.

Clinical management impact:

Proportion of patients with treatment change following serial PSMA PET, with exact binomial 95% CI.

Multiple testing:

Benjamini-Hochberg procedure for secondary endpoints (FDR 5%). No adjustment for exploratory subgroup analyses.

Data Management and Quality Assurance Data will be stored centrally in a REDCap database with 3-step authentication. Data entry every 3-6 months. PSMA PET images centrally reviewed by two nuclear medicine physicians blinded to clinical outcomes, using standardized software (MIM Software, Hermes, or institutional platform). Inter-reader agreement for lesion counts and SUVmax measurement will be assessed using intraclass correlation coefficients (ICC).

• Study Type: Observational
• Enrollment (Estimated): 110

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
      • Contact: Zhiyong Lv, MD.; Phone Number: +86 18700919857; Email: 1531769428@qq.com
      • Principal Investigator: Zhiyong Lv, MD.
  • 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 Hospital
      • Contact: Weihong Zhao, MD.; Phone Number: +86 18700919857; Email: 1531769428@qq.com
      • Principal Investigator: Weihong Zhao, MD.
    • Xi'an, Shaanxi, China
      • 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
      • Recruiting
      • Xijing 986 Hospital
      • Contact: Wuhe Zhang, MD.; Phone Number: +86 18700919857; Email: 1531769428@qq.com
      • Principal Investigator: Wuhe Zhang, MD.
    • 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
      • Principal Investigator: Jixue Gao, MD.
      • Contact: Jixue Gao; Phone Number: +86 18700919857; Email: 1531769428@qq.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

A consecutive series of approximately 110 patients (targeting 100 evaluable after 10% loss to follow-up) with newly diagnosed, histologically confirmed clinically significant prostate cancer (Gleason score ≥7), treatment-naïve, recruited from multiple centers. All patients undergo baseline PSMA PET/CT prior to any treatment. A second PSMA PET/CT is performed either at PSA recurrence (defined as PSA ≥0.2 ng/mL after radical prostatectomy or PSA rise ≥2 ng/mL above nadir after radiotherapy) or at 12-24 months after treatment completion for those without biochemical recurrence. Patients receive standard clinical treatments per physician discretion. This single cohort is used to evaluate serial PSMA PET for treatment response monitoring.

Description

Inclusion Criteria

1. Newly diagnosed, histologically confirmed prostate cancer with Gleason score ≥7 (clinically significant prostate cancer).
2. Planned to receive curative-intent therapy (radical prostatectomy or radiotherapy) or systemic therapy (androgen deprivation therapy, chemotherapy, or combination).
3. Undergo baseline PSMA PET/CT imaging prior to any prostate cancer-related treatment.
4. Age ≥18 years.
5. Willing and able to comply with the follow-up schedule, including the second PSMA PET/CT scan.
6. Provide written informed consent.

Exclusion Criteria

1. Any prior prostate cancer treatment (including hormonal therapy, radiotherapy, chemotherapy, or surgery) before baseline PSMA PET/CT.
2. 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).
3. Other active malignancy within the past two years, excluding non-melanoma skin cancer.
4. Severe comorbidities or conditions that, in the opinion of the investigator, could interfere with study compliance or pose a significant risk to the patient.
5. Unable or unwilling to provide informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute and relative change in SUVmax from baseline to follow-up PSMA PET	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 (%).	Baseline and follow-up (12-24 months post-treatment or at time of PSA recurrence); overall assessment up to 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with treatment strategy change following serial PSMA PET	Description: The proportion of patients in whom serial PSMA PET findings lead to a change in clinical management (treatment intensification, switch, or de-escalation). Exact binomial 95% confidence interval will be reported. Measurement tool and unit: Clinical management decision recorded by investigator; proportion (%) of patients.	Up to 2 years
Absolute and relative change in number of PSMA-avid lesions (supportive endpoint)	Description: Total number of PSMA-avid lesions (primary tumor, nodal metastases, bone metastases) counted using standardized rules. Absolute change (Δcount) and relative change (percentage) calculated. Correlation with treatment response categories (composite reference standard) assessed by Spearman correlation and negative binomial regression. This is a supportive endpoint; no multiplicity adjustment applied. Measurement tool and unit: PSMA PET/CT with standardized lesion counting rules; integer (count) and percentage (%).	Baseline and follow-up (12-24 months or at PSA recurrence); overall up to 2 years.
Agreement between PSMA PET response and PSA50 response	Description: PSA50 response defined as ≥50% decline in PSA from baseline to follow-up (binary). PSMA PET response defined as ≥30% decrease in SUVmax (binary). Cohen's kappa coefficient with 95% CI, percent agreement, and PABAK will be reported. Measurement tool and unit: PSA measured in ng/mL by clinical laboratory; binary category.	Up to 2 years
Agreement between PSMA PET response and PSA90 response	Description: PSA90 response defined as ≥90% decline in PSA from baseline to follow-up (binary). PSMA PET response same as above. Cohen's kappa with 95% CI, percent agreement, and PABAK reported. Measurement tool and unit: PSA measured in ng/mL by clinical laboratory; binary category.	Up to 2 years
Association of PSMA PET parameters with progression-free survival (PFS)(exploratory)	Description: PFS defined as time from treatment initiation to first evidence of radiographic progression (per composite reference standard), PSA progression (per PCWG3 criteria), or death from any cause. Cox proportional hazards regression will assess hazard ratios for baseline SUVmax, baseline lesion count, and ΔSUVmax, adjusting for clinical covariates (PSA, Gleason, treatment type). Hazard ratios with 95% CI and p-values will be reported. Measurement tool and unit: PSMA PET parameters and clinical follow-up; time-to-event in months	Up to 2 years
Association of baseline and follow-up PSMA PET parameters with time to castration resistance (exploratory, ADT patients only)	Description: For patients receiving androgen deprivation therapy (ADT) as part of initial treatment, time to castration resistance defined per PCWG3 criteria (serum testosterone <50 ng/dL plus PSA progression or radiographic progression). Cox regression will assess hazard ratios for baseline and follow-up PSMA PET parameters. Measurement tool and unit: PSMA PET parameters and clinical follow-up; time-to-event in months	Up to 2 years
Subgroup analyses of PSMA PET parameter changes (exploratory)	Description: For subgroups defined by treatment type (radiotherapy/ADT/chemotherapy), baseline disease burden (oligometastatic ≤3 lesions vs polymetastatic >3), and Gleason grade group (≤7 vs ≥8), descriptive statistics (median, IQR) of ΔSUVmax and Δlesion count will be provided, and logistic regression will explore association with response. No multiplicity adjustment. Measurement tool and unit: PSMA PET parameters; continuous (SUVmax, count) and binary subgroups.	Up to 2 years
Inter-reader agreement for PSMA-avid lesion counts (exploratory)	Description: Two independent nuclear medicine physicians will count lesions. Intraclass correlation coefficient (ICC, two-way random, absolute agreement) with 95% CI, and Cohen's kappa for presence/absence of any lesion will be reported. Measurement tool and unit: PSMA PET/CT images; ICC (unitless) and kappa.	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

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2021
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: April 20, 2026
• First Posted (Actual): April 28, 2026

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Prostate Cancer; High-Risk; PSMA PET; Treatment Response; Therapy Monitoring
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: KY20262013-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