Combining PSMA-PET and PROMISE to re-define disease stage and risk in patients with prostate cancer: a multicentre retrospective study

• Published in: The lancet oncology 2024-09, Vol.25 (9), p.1188-1201
• Main Authors: Karpinski, Madeleine J, Hüsing, Johannes, Claassen, Kevin, Möller, Lennart, Kajüter, Hiltraud, Oesterling, Florian, Grünwald, Viktor, Umutlu, Lale, Kleesiek, Jens, Telli, Tugce, Merkel-Jens, Anja, Hüsing, Anika, Kesch, Claudia, Herrmann, Ken, Eiber, Matthias, Hoberück, Sebastian, Meyer, Philipp T, Kind, Felix, Rahbar, Kambiz, Schäfers, Michael, Stang, Andreas, Hadaschik, Boris A, Fendler, Wolfgang P
• Format: Article
• Language: English
• Subjects: Aged; Antigens; Antigens, Surface - analysis; Atrophy; Bone imaging; Bone marrow; Castration; Collaboration; Germany - epidemiology; Glutamate Carboxypeptidase II - metabolism; Hospitals; Humans; Localization; Lymph nodes; Lymphatic system; Male; Medical prognosis; Metastases; Metastasis; Middle Aged; Neoplasm Staging; Nomograms; Nuclear medicine; Patients; Positron emission tomography; Prognosis; Prostate cancer; Prostatic Neoplasms - diagnostic imaging; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; Regression analysis; Retrospective Studies; Risk Assessment; Risk Factors; Risk groups; Survival; Tumors; Urology; Variables
• ISSN: 1470-2045; 1474-5488; 1474-5488
• DOI: 10.1016/S1470-2045(24)00326-7

Prostate-specific membrane antigen (PSMA)-PET was introduced into clinical practice in 2012 and has since transformed the staging of prostate cancer. Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria were proposed to standardise PSMA-PET reporting. We aimed to compare the prognostic value of PSMA-PET by PROMISE (PPP) stage with established clinical nomograms in a large prostate cancer dataset with follow-up data for overall survival. In this multicentre retrospective study, we used data from patients of any age with histologically proven prostate cancer who underwent PSMA-PET at the University Hospitals in Essen, Münster, Freiburg, and Dresden, Germany, between Oct 30, 2014, and Dec 27, 2021. We linked a subset of patient hospital records with patient data, including mortality data, from the Cancer Registry North-Rhine Westphalia, Germany. Patients from Essen University Hospital were randomly assigned to the development or internal validation cohorts (2:1). Patients from Münster, Freiburg, and Dresden University Hospitals were included in an external validation cohort. Using the development cohort, we created quantitative and visual PPP nomograms based on Cox regression models, assessing potential PPP predictors for overall survival, with least absolute shrinkage and selection operator penalty for overall survival as the primary endpoint. Performance was measured using Harrell's C-index in the internal and external validation cohorts and compared with established clinical risk scores (International Staging Collaboration for Cancer of the Prostate [STARCAP], European Association of Urology [EAU], and National Comprehensive Cancer Network [NCCN] risk scores) and a previous nomogram defined by Gafita et al (hereafter referred to as GAFITA) using receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) estimates. We analysed 2414 male patients (1110 included in the development cohort, 502 in the internal cohort, and 802 in the external validation cohort), among whom 901 (37%) had died as of data cutoff (June 30, 2023; median follow-up of 52·9 months [IQR 33·9–79·0]). Predictors in the quantitative PPP nomogram were locoregional lymph node metastases (molecular imaging N2), distant metastases (extrapelvic nodal metastases, bone metastases [disseminated or diffuse marrow involvement], and organ metastases), tumour volume (in L), and tumour mean standardised uptake value. Predictors in the visual PPP nomogram we