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

N/AActive Not RecruitingNCT07608419

General University Hospital, Prague400 enrolled

Overview

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 Type

OBSERVATIONAL

Enrollment

400

Conditions

Prostate Cancer High Risk Prostate Cancer PSMA PET Staging

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: Data collected at the time of result of PSMA PET/CT imaging, approximately 1 month after.

Secondary Outcomes

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.

Time frame: 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.

Time frame: From the date of treatment with curative intent up to 10 years.