New prostate cancer risk groups by PSMA-PET (PPP3): an international, retrospective, registry-based cohort study

Research output: Contribution to journal › Research article › Contributed › peer-review

Contributors

  • PROMISE Registry Group - (Author)
  • Madeleine J. Karpinski - , University Hospital Essen, University of Münster, University of Cologne (Author)
  • Caner Civan - , University Hospital Essen, University of Cologne (Author)
  • Isabel Rauscher - , Technical University of Munich (Author)
  • Osman Güven - , Technical University of Munich (Author)
  • Matthias Eiber - , Technical University of Munich, Bavarian Center for Cancer Research (BZKF) (Author)
  • Sebastian Hoberück - , Department of Nuclear Medicine, University Hospital Carl Gustav Carus Dresden (Author)
  • Matthias Miederer - , Department of Nuclear Medicine, National Center for Tumor Diseases Dresden (NCT/UCC), University Hospital Carl Gustav Carus Dresden (Author)
  • Ralph A. Bundschuh - , Department of Nuclear Medicine, University Hospital Carl Gustav Carus Dresden (Author)
  • Tobias Hölscher - , Department of Radiotherapy and Radiooncology, University Hospital Carl Gustav Carus Dresden (Author)
  • Jeremie Calais - , University of California at Los Angeles (Author)
  • Lela Theus - , University of California at Los Angeles (Author)
  • Andrew T. Nguyen - , University of California at Los Angeles (Author)
  • Helen Scholtissek - , Augsburg University (Author)
  • Constantin Lapa - , Augsburg University (Author)
  • Andrea Di Giorgio - , University of Bologna (Author)
  • Andrea Farolfi - , IRCCS Azienda Ospedaliero-Universitaria di Bologna (Author)
  • Dominic Ufton - , University of Cologne (Author)
  • Alexander Drzezga - , University of Cologne (Author)
  • Jolanta Kunikowska - , Medical University of Warsaw (Author)
  • Kacper Pełka - , Medical University of Warsaw (Author)
  • Laura Evangelista - , IRCCS Istituto Clinico Humanitas - Rozzano (Milano), Humanitas University (Author)
  • Glenn Bauman - , Western University (Author)
  • Göksel Alçın - , Istanbul Traınıng And Research Hospıtal (Author)
  • Stephan Beintner-Skawran - , University of Zurich (Author)
  • Mohd Fazrin Mohd Rohani - , Kuala Lumpur Hospital, Institut Kanser Negara (Author)
  • Jonathan Miksch - , Ulm University (Author)
  • Anika Hüsing - , University Hospital Essen (Author)
  • Claudia Kesch - , University Hospital Essen (Author)
  • Ken Herrmann - , University Hospital Essen (Author)
  • Martin Stuschke - , University Hospital Essen (Author)
  • Lale Umutlu - , University Hospital Essen (Author)
  • Andrei Gafita - , Johns Hopkins Medicine (Author)
  • Michael S. Hofman - , Peter Maccallum Cancer Centre, University of Melbourne (Author)
  • Thomas A. Hope - , University of California at San Francisco (Author)
  • Karolien Goffin - , KU Leuven (Author)
  • Felix Kind - , University Medical Center Freiburg (Author)
  • Daniele A. Pizzuto - , A. Gemelli University Hospital Foundation IRCCS (Author)
  • Timo F.W. Soeterik - , Utrecht University, St. Antonius Hospital (Author)
  • Halil Kömek - , University of Health Sciences (Author)
  • Louise Emmett - , St. Vincent's Hospital Sydney (Author)
  • Andrej Vondrak - , IZOTOPCENTRUM, s.r.o. – Nuclear Medicine Centrum (Author)
  • Tomas Pinter - , IZOTOPCENTRUM, s.r.o. – Nuclear Medicine Centrum (Author)
  • Francesco Lanfranchi - , University of Genoa (Author)
  • Matteo Bauckneht - , University of Genoa, IRCCS San Martino Polyclinic Hospital (Author)
  • Lena M. Unterrainer - , Ludwig Maximilian University of Munich (Author)
  • Adrien Holzgreve - , University of California at Los Angeles, Ludwig Maximilian University of Munich (Author)

Abstract

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. Funding German Research Foundation, Prostate Cancer Foundation, Innovative Health Initiative Joint Undertaking, Novartis, AstraZeneca, and Amgen.

Details

Original languageEnglish
Pages (from-to)480-490
Number of pages11
JournalThe Lancet Oncology
Volume27
Issue number4
Publication statusPublished - Apr 2026
Peer-reviewedYes

External IDs

PubMed 41819113
ORCID /0000-0003-1776-9556/work/224858699

Keywords

Sustainable Development Goals

ASJC Scopus subject areas