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

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.

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.

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.

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.

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.

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.

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.