Predictors of Nodal and Distant Metastatic Disease Detected by PSMA PET in Treatment-Naïve High-Risk Prostate Cancer: A Czech Multicentre Cohort Study (CZECH-PSMA)

Prostate cancer is the second most common malignancy worldwide and the fifth leading cause of male cancer-related mortality. Approximately 15% of localized cases are classified as high-risk for biochemical recurrence. These patients frequently harbour occult metastases undetected by conventional imaging (CT and bone scintigraphy). Consequently, PSMA PET has revolutionized primary staging and is strongly recommended by EAU guidelines. In the Czech Republic, a transition toward a "PSMA-first" pathway is evident, where molecular imaging increasingly replaces conventional modalities. This "stage-migration" identifies a new cohort of miN1/M1 patients previously classified as having localized disease. However, PSMA PET is a resource-demanding modality and not yet universally available. To optimize its utility, identifying which combinations of routinely available parameters predict metastatic disease and characterizes this new cohort is essential. Furthermore, real-world evidence regarding early oncological outcomes within this PSMA-only framework is limited. This multicentre cohort study aims to define a multiparametric predictive model for PSMA-detected metastases and evaluate the real-world therapeutic trajectories and follow-up outcomes of this newly defined high-risk population. Integrating clinical, biological, and molecular data, seeks to refine patient selection and provide a longitudinal perspective on the "PSMA-first" diagnostic era.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Cancer; High Risk Prostate Cancer; PSMA PET; Staging
• Intervention / Treatment: Diagnostic test: PSMA PET

• Study Type: Observational
• Enrollment (Estimated): 400

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Persons: Male patients aged ≥ 18 years with histologically confirmed prostate adenocarcinoma. Place: The Czech Republic, including patients diagnosed and treated in Urological and ahiliated Nuclear Medicine Departments.

Time period (Study Window): January 1, 2016 to December 31, 2025, capturing the transition toward molecular imaging in primary staging.

Selection Criteria: Patients with histologically confirmed high-risk prostate cancer according to EAU guidelines who underwent primary staging with PSMA PET within the study window.

Description

Inclusion Criteria

Male patients will be included if:

• Male patients aged ≥ 18 years with histologically confirmed prostate adenocarcinoma,
• high-risk disease defined as ISUP GG ≥ 4 and/or PSA ≥ 20 ng/ml and/or clinical stage assessed by DRE ≥ cT2c,
• PSMA PET performed for primary staging within study window.

Exclusion Criteria

Patients with:

• definitive local treatment (e.g., radical prostatectomy or radiation therapy) or systemic treatment (e.g., androgen deprivation therapy) administered prior to primary staging with PSMA PET,
• low or intermediate-risk PCa as defined by failing to meet any of the inclusionary high-risk parameters,
• incomplete or fragmented medical records that preclude the accurate extraction of primary staging parameters (PSA, ISUP GG, clinical T-stage) or PSMA PET results (miN/miM status),
• active malignancy requiring systemic treatment at the time of PSMA PET.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
High-risk localized or locally advanced PCa before treatment	Diagnostic test: PSMA PET; PSMA PET with different the use radiotracers as primary staging of high risk localized or locally advanced PCa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Receiver Operating Characteristic (AUC ROC) [scale 0 to 1] of multiparametric model for miN1 and/or miM1 on PSMA (prostate specific membrane antigen) PET (positron emission tomography) according to PROMISE (prostate cancer) V2 criteria.	This predictive model aggregates heterogeneous predictors into a single numerical probability score to determine the presence of metastasis by multivariate logistical regression. The model will include: serum PSA (prostate specific antigen) [μg/ml] and/or PSA density [μg/ml/cc], clinical T stage [T1a/b/c, T2a/b/c, T3a/b, T4], prostate biopsy ISUP GG - International Society of Urology Pathology Grade Group [1/2/3/4/5], and the presence of a cribriform growth pattern, multiparametric MRI (magnetic resonance imaging) PI-RADS (Prostate Imaging Reporting and Data System) v2.1 score [1/2/3/4/5], as well as SUVmax (maximum standardized uptake value) [g/ml] and PSMA PET total tumor volume [ml] of the primary intraprostatic lesion. Higher scores/values indicate more aggressive disease.	Data collected at the time of result of PSMA PET/CT imaging, approximately 1 month after.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of miT and miN stage migration between PSMA PET (according to PROMISE V2) and final histopathology from radical prostatectomy.	The proportion of participants whose pathological stage pT and pN differs from the molecular imaging stage miT and miN. Upstaging: Percentage of cases where pathology reveals more advanced disease than PET (e.g., miT2 to pT3a). Downstaging: Percentage of cases where pathology reveals less extensive disease than PET (e.g., miN1 to pN0). Total Concordance: Percentage of cases where miT/N and pT/N are identical.	At the time of surgery (approximately 2-6 weeks post-imaging).
Prognostic Value of Combined Molecular and Clinicopathological Markers for Early Oncological Outcomes	Evaluation of the combined predictive utility of PSMA SUVmax (maximum standardized uptake value) [g/ml] and / or phi (the Prostate Health Index) and / or the presence of a cribriform growth pattern for forecasting early oncological outocmes including biochemical persistence (defined as PSA ≥ 0.1 ng/mL at 6-8 weeks post-surgery) and biochemical recurrence (defined as two consecutive PSA values ≥ 0.2 ng/mL after radical prostatectomy or ≥ 2 ng/mL above nadir after radical radiotherapy). The study also measures the impact of these integrated parameters on progression-free survival and overall survival. Predictive accuracy is quantified through multivariable modeling to determine the additive value of molecular imaging over standard clinical parameters.	From the date of treatment with curative intent up to 10 years.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of clinical management changes based on PSMA PET/CT compared to conventional imaging	This measure assesses the proportion of participants whose treatment plan is modified following PSMA PET/CT staging relative to the strategy established by conventional imaging. A management change is defined as a transition in clinical intent, such as moving from local curative therapy to systemic treatment due to the discovery of metastatic disease. The study records the rate at which molecular imaging findings lead to a change in the final management decision compared to standard-of-care imaging.	From the date of initial conventional imaging to the initiation of the final treatment plan (approximately 4-12 weeks).
Rate of interobserver agreement between local and central expert reviews using standardized PROMISE V2 criteria	The level of consistency between local site investigators and central expert reviewers is assessed through the comparison of PSMA PET/CT molecular staging findings. Agreement is quantified using Cohen's kappa coefficient to evaluate the reproducibility of the PROMISE V2 criteria.	From the date of initial imaging until the completion of centralized review (approximately 3 months).
Predictive accuracy of preoperative markers for adverse pathological features at radical prostatectomy	This measure assesses the ability of PSMA PET findings (SUVmax of prostate and seminal vesicles and / or total PSMA volume) and clinical parameters (PSA-D and / or cribriform pattern) to predict the presence of high-risk disease features in the final surgical specimen. Adverse pathological features are defined as the presence of pT3 (pathological T stage 3) and final ISUP (International Society of Urological Pathology) Grade Group ≥ 4, or pelvic lymph node metastasis (pN1). The predictive performance is reported using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity to quantify the diagnostic accuracy of preoperative staging compared to the gold-standard histopathology.	At the time of surgery (approximately 2-6 weeks post-imaging)
Rate of biochemical recurrence-free survival in the oligometastatic subgroup of this cohort primarly staged with PSMA PET	This outcome measure determines the proportion of participants in the oligometastatic subgroup who remain free of biochemical recurrence following primary treatment. Biochemical recurrence is defined as the occurrence of two consecutive PSA values ≥ 0.2 ng/mL. By aggregating these clinical, diagnostic, and oncological parameters, the study evaluates the total impact of PSMA PET/CT on the standard of care and its influence on subsequent clinical management.	From the date of primary treatment up to 10 years.

Collaborators and Investigators

• Sponsor: General University Hospital, Prague
• Collaborators: University Hospital Olomouc; Ústřední fakultní vojenská nemocnice, Praha, Czechia; Nemocnice České Budějovice, České Budějovice, Czechia; Masaryk University; University Hospital, Motol; County Hospital Liberec, Liberec, Czech Republic

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: April 2, 2026
• First Submitted That Met QC Criteria: May 19, 2026
• First Posted (Actual): May 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• 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: 49/26 S-IV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: If asked for other studies e.g. systematic review and metaanalysis.

Drug and device information, study documents

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