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Updated Prostate Cancer Risk Groups by Prostate-specific Membrane Antigen Positron Emission Tomography Prostate Cancer Molecular Imaging Standardized Evaluation (PPP2) : Results from an International Multicentre Registry Study

Karpinski, Madeleine J. ; Rahbar, Kambiz ; Bögemann, Martin ; Nikoukar, Laya Rahbar ; Schäfers, Michael ; Hoberück, Sebastian ; Miederer, Matthias ; Hölscher, Tobias ; Rasul, Sazan and Miszczyk, Marcin , et al. (2025) In European Urology
Abstract

Background and objective: We established prognostic nomograms incorporating prostate-specific membrane antigen (PSMA) positron emission tomography (PET) parameters standardised by Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE; PPP1). Here, we develop an updated PPP2 risk score from a large international multicentre registry study. Methods: We included 6128 prostate cancer patients who underwent PSMA-PET at 20 hospitals in Europe, USA, and Australia between 2013 and 2022. Investigator sites were split 2:1 into the development (4044 patients) and validation (2084 patients) cohorts. We created nomograms of version 2 (PPP2) based on Cox regression models with the least absolute shrinkage and selection operator penalty... (More)

Background and objective: We established prognostic nomograms incorporating prostate-specific membrane antigen (PSMA) positron emission tomography (PET) parameters standardised by Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE; PPP1). Here, we develop an updated PPP2 risk score from a large international multicentre registry study. Methods: We included 6128 prostate cancer patients who underwent PSMA-PET at 20 hospitals in Europe, USA, and Australia between 2013 and 2022. Investigator sites were split 2:1 into the development (4044 patients) and validation (2084 patients) cohorts. We created nomograms of version 2 (PPP2) based on Cox regression models with the least absolute shrinkage and selection operator penalty for overall survival (development cohort). Performance of both nomograms was measured using Harrell's C-index and calibration plots and a head-to-head comparison with the National Comprehensive Cancer Network (NCCN) risk score by receiver operating characteristic curves (validation cohort). Key findings and limitations: Predictors were distant metastases (extrapelvic nodal metastases [M1a], bone metastases [M1b], and visceral metastases [M1c]), PSMA expression score, and total lesion count (visual PPP2) or total tumour volume (quantitative PPP2). C-indices (95% confidence interval) in the validation cohort were 0.80 (0.78–0.82; visual) and 0.80 (0.79–0.82; quantitative), respectively. Accuracy of both the PPP2 nomograms was superior to the NCCN risk score (n = 1034, area under the curve 0.84 vs 0.76; p < 0.001). The retrospective design represents a limitation of the study. Conclusions and clinical implications: PPP nomograms were improved in an international multicentre study to predict accurately the 3- and 5-yr overall survival probabilities of prostate cancer. PPP2 yielded superior accuracy to the NCCN risk score. A free software tool has been created for PROMISE and PPP2 assessments (promise-pet.org).

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Contribution to journal
publication status
epub
subject
keywords
Overall survival, Prognosis, Prostate cancer, Prostate Cancer Molecular Imaging Standardized Evaluation nomogram, Prostate-specific membrane antigen positron emission tomography
in
European Urology
publisher
Elsevier
external identifiers
  • scopus:105004303105
ISSN
0302-2838
DOI
10.1016/j.eururo.2025.04.017
language
English
LU publication?
yes
id
cc226d16-9483-49f9-b581-e01af303e88a
date added to LUP
2025-09-26 13:43:12
date last changed
2025-09-26 13:43:57
@article{cc226d16-9483-49f9-b581-e01af303e88a,
  abstract     = {{<p>Background and objective: We established prognostic nomograms incorporating prostate-specific membrane antigen (PSMA) positron emission tomography (PET) parameters standardised by Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE; PPP1). Here, we develop an updated PPP2 risk score from a large international multicentre registry study. Methods: We included 6128 prostate cancer patients who underwent PSMA-PET at 20 hospitals in Europe, USA, and Australia between 2013 and 2022. Investigator sites were split 2:1 into the development (4044 patients) and validation (2084 patients) cohorts. We created nomograms of version 2 (PPP2) based on Cox regression models with the least absolute shrinkage and selection operator penalty for overall survival (development cohort). Performance of both nomograms was measured using Harrell's C-index and calibration plots and a head-to-head comparison with the National Comprehensive Cancer Network (NCCN) risk score by receiver operating characteristic curves (validation cohort). Key findings and limitations: Predictors were distant metastases (extrapelvic nodal metastases [M1a], bone metastases [M1b], and visceral metastases [M1c]), PSMA expression score, and total lesion count (visual PPP2) or total tumour volume (quantitative PPP2). C-indices (95% confidence interval) in the validation cohort were 0.80 (0.78–0.82; visual) and 0.80 (0.79–0.82; quantitative), respectively. Accuracy of both the PPP2 nomograms was superior to the NCCN risk score (n = 1034, area under the curve 0.84 vs 0.76; p &lt; 0.001). The retrospective design represents a limitation of the study. Conclusions and clinical implications: PPP nomograms were improved in an international multicentre study to predict accurately the 3- and 5-yr overall survival probabilities of prostate cancer. PPP2 yielded superior accuracy to the NCCN risk score. A free software tool has been created for PROMISE and PPP2 assessments (promise-pet.org).</p>}},
  author       = {{Karpinski, Madeleine J. and Rahbar, Kambiz and Bögemann, Martin and Nikoukar, Laya Rahbar and Schäfers, Michael and Hoberück, Sebastian and Miederer, Matthias and Hölscher, Tobias and Rasul, Sazan and Miszczyk, Marcin and Lanfranchi, Francesco and Bauckneht, Matteo and Pfob, Christian H. and Kind, Felix and Goffin, Karolien and Hüsing, Anika and Kesch, Claudia and Herrmann, Ken and Stuschke, Martin and Gafita, Andrei and Hüsing, Johannes and Calais, Jeremie and Hofman, Michael S. and Hope, Thomas A. and Miksch, Jonathan and Soeterik, Timo F.W. and Di Giorgio, Andrea and Farolfi, Andrea and Bjartell, Anders and Trägårdh, Elin and Unterrainer, Lena M. and Holzgreve, Adrien and Sheikh, Gabriel T. and Rauscher, Isabel and Eiber, Matthias and Hadaschik, Boris A. and Fendler, Wolfgang P.}},
  issn         = {{0302-2838}},
  keywords     = {{Overall survival; Prognosis; Prostate cancer; Prostate Cancer Molecular Imaging Standardized Evaluation nomogram; Prostate-specific membrane antigen positron emission tomography}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{European Urology}},
  title        = {{Updated Prostate Cancer Risk Groups by Prostate-specific Membrane Antigen Positron Emission Tomography Prostate Cancer Molecular Imaging Standardized Evaluation (PPP2) : Results from an International Multicentre Registry Study}},
  url          = {{http://dx.doi.org/10.1016/j.eururo.2025.04.017}},
  doi          = {{10.1016/j.eururo.2025.04.017}},
  year         = {{2025}},
}