Open Access

Background Prostate-specific membrane antigen (PSMA)-PET usage in patients with prostate cancer is growing rapidly. Thus, novel risk-group definitions based on PSMA-PET are urgently needed for guidelines, clinical use, and trial study design. We report improved risk classification based on PSMA-PET Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE; PPP) nomograms (PPP3) to prognosticate 3-year, 5-year, and 7-year overall survival. Methods In this international, retrospective, registry-based cohort study, we collected data from the PROMISE PET registry with ongoing overall survival follow-up. Male patients (aged ≥18 years) with histological proven prostate cancer at any disease stage and any performance status, who underwent any PSMA-PET between Dec 6, 2012, and June 26, 2024, were included in the registry. Patients with neuroendocrine pattern or metastasised or disseminated malignancy other than prostate cancer were excluded. 35 investigator sites in Europe, Asia, Australia, North America, and South America were split pairwise (2:1) into development and validation cohorts. Entire investigator sites were split pairwise according to their site characteristics (ie, number of patients per disease group, country, follow-up). The primary study objective was overall survival. PPP3 nomograms were created based on Cox regression models with least absolute shrinkage and selection operator penalty to prognosticate 3-year, 5-year, and 7-year overall survival. Calibration curves and Harrell's c indices were applied and head-to-head comparison with clinical risk scores separated for each disease subgroup was conducted. Based on the visual PPP3 nomogram, a simplified risk-stratification table was created. Findings We analysed 11 154 patients and 7253 were included in the development cohort and 3901 in the validation cohort. Median follow-up to censoring or death was 4·9 years (IQR 3·5–6·6). Clinical disease group and PROMISE metrics were combined into visual and quantitative PPP3 nomograms, respectively. C indices were 0·83 (95% CI 0·82–0·84) for the visual nomogram and 0·84 (0·82–0·85) for the quantitative nomogram. Both nomograms and the simplified risk stratification table were accurate and equal or superior compared with established clinical risk scores (International Staging Collaboration for Cancer of the Prostate, European Association of Urology, a nomogram defined by Gafita and colleagues, and National Comprehensive Cancer Network). Interpretation We present new risk nomograms by PROMISE along with a simple table to prognosticate 3-year, 5-year, and 7-year overall survival in prostate cancer. PROMISE and PPP3 assessments are freely available online for global implementation.

Context: Prostate-specific membrane antigen (PSMA) targeting positron emission tomography (PET) is emerging to become a reference imaging tool for the staging and restaging of patients with prostate cancer for both clinical routine and trials. The prostate cancer molecular imaging standardized evaluation (PROMISE) criteria have been proposed as a framework for whole-body staging (molecular imaging TNM staging, denoted miTNM staging) to describe the prostate cancer disease extent on PSMA-PET. Objective: To create a comprehensive and integrated framework for PSMA-PET image interpretation and reporting. Evidence acquisition: We propose the PROMISE V2 framework, which integrates an updated miTNM system, improved assessment of local disease, and a slightly modified PSMA-expression score for clinical routine. We have added a response monitoring framework defining qualitative and quantitative parameters to be recorded for a longitudinal assessment in clinical trials. Evidence synthesis: We provide a comprehensive literature review on the current use of the PROMISE framework in clinical research and prospective trials. PROMISE variables demonstrate a clear association with survival. PSMA expression assessed by the PSMA-expression score was used in several trials, and a low PSMA-expression score is a negative prognosticator of overall survival after 177Lu-PSMA radioligand therapy. The proposed imaging parameters recorded for response assessment in clinical trials can be utilized to determine response according to PSMA-PET progression (PPP) or Response Evaluation Criteria in PSMA-PET/Computed Tomography (RECIP) frameworks, but also future response criteria. Conclusions: PROMISE V2 offers standardized reporting of disease extent for clinical routine and research. Parameters recorded within clinical trials facilitate objective response assessment. Patient summary: Prostate-specific membrane antigen (PSMA) targeting positron emission tomography (PET) has become a standard imaging examination for prostate cancer. We propose a comprehensive framework for the analysis and reporting of PSMA-PET findings that will improve the communication between imaging experts and uro-oncologists.