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. 2025 May 2:S0302-2838(25)00249-0.
doi: 10.1016/j.eururo.2025.04.017. Online ahead of print.

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

Madeleine J Karpinski  1 , Kambiz Rahbar  2 , Martin Bögemann  3 , Laya Rahbar Nikoukar  2 , Michael Schäfers  2 , Sebastian Hoberück  4 , Matthias Miederer  5 , Tobias Hölscher  4 , Sazan Rasul  6 , Marcin Miszczyk  7 , Francesco Lanfranchi  8 , Matteo Bauckneht  9 , Christian H Pfob  10 , Felix Kind  11 , Karolien Goffin  12 , Anika Hüsing  13 , Claudia Kesch  14 , Ken Herrmann  15 , Martin Stuschke  16 , Andrei Gafita  17 , Johannes Hüsing  18 , Jeremie Calais  19 , Michael S Hofman  20 , Thomas A Hope  21 , Jonathan Miksch  22 , Timo F W Soeterik  23 , Andrea Di Giorgio  24 , Andrea Farolfi  25 , Anders Bjartell  26 , Elin Trägårdh  27 , Lena M Unterrainer  28 , Adrien Holzgreve  29 , Gabriel T Sheikh  30 , Isabel Rauscher  31 , Matthias Eiber  32 , Boris A Hadaschik  14 , Wolfgang P Fendler  15
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Free article

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

Madeleine J Karpinski et al. Eur Urol. .
Free article

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 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).

Keywords: Overall survival; Prognosis; Prostate Cancer Molecular Imaging Standardized Evaluation nomogram; Prostate cancer; Prostate-specific membrane antigen positron emission tomography.

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