1609P - PSMA-PET and PROMISE re-define stage and risk in patients with prostate cancer

Background

Prostate-Specific Membrane Antigen Positron-Emission-Tomography (PSMA-PET) was introduced in 2012 and has since significantly transformed the staging of prostate cancer. PROMISE criteria were proposed to standardize PSMA-PET reporting. Here we compare the prognostic value of PSMA-PET by PROMISE (PPP) stage head-to-head with established clinical risk scores in a large prostate cancer dataset with overall survival follow-up.

Methods

All prostate cancer patients, who underwent PSMA-PET at the Essen University Hospital between 2014 and 2021, were randomly split into development and validation cohorts (2:1). Patients from University Hospitals in Münster, Freiburg and Dresden, Germany, were included as external validation cohort. We created a quantitative and visual PPP Nomogram based on Cox regression models with LASSO penalty for overall survival on the Development cohort. Accuracy was measured using C-index and head-to-head comparison to clinical risk scores using ROC-curves.

Results

We analysed 2414 patients (1110 development, 502 internal and 802 external validation) with 901 (37.3%) deaths across all disease stages. Predictors in the quantitative PPP Nomogram were locoregional lymph node metastases (miN2), distant metastases (miM1a, miM1b pattern, miM1c), tumour volume, and tumour SUVmean. The visual PPP Nomogram includes distant metastases, and total tumour lesion count. C-indices in the internal and external validation cohorts were 0.80 and 0.77 (quantitative) or 0.78 and 0.77 (visual), respectively. The quantitative PPP Nomogram was superior to STARCAP at initial staging (n=139; AUC: 0.73 vs. 0.54; p=0.02), to EAU risk score at biochemical recurrence (n=412; AUC: 0.69 vs. 0.52; p<0.001) and to NCCN subgroups at any timepoint (n=1534; AUC: 0.81 vs. 0.74; p<0.001). The visual PPP Nomogram was superior to EAU at biochemical recurrence (n=414; AUC: 0.64 vs. 0.52; p<0.001) and NCCN subgroups at any timepoint (n=1544; AUC: 0.79 vs. 0.73; p<0.001).

Conclusions

Our PPP Nomograms accurately stratify high vs. low risk groups for overall survival in early and late stages of prostate cancer and yield better prediction than established clinical risk tools. Validation with long-term follow-up is ongoing (NCT06320223, promise-pet.com).

Clinical trial identification

NCT06320223.

Editorial acknowledgement

Legal entity responsible for the study

University Hospital Essen.

Funding

Cancer Registry North-Rhine Westphalia, Germany.

Disclosure

W.P. Fendler: Financial Interests, Personal, Advisory Board: Janssen, Calyx, Bayer, Novartis; Financial Interests, Personal, Invited Speaker: Telix, GE Healthcare, Eczacıbaşı Monrol, Abx, Amgen, Urotrials; Financial Interests, Institutional, Local PI: SOFIE Bioscience. M. Karpinski: Other, Personal, Stocks/Shares: Bayer. V. Gruenwald: Financial Interests, Personal, Invited Speaker: Amgen, Astellas, AstraZeneca, BMS, EISAI, Ipsen, Janssen-Cilag, MSD, Merck Serono, Novartis, Pfizer, Gilead; Financial Interests, Personal, Advisory Board: Apogepha, BMS, Debiopharm, EISAI, MSD, Merck Serono, Oncorena, PCI Biotech, Pfizer, Roche, Cureteq, Synthekine; Financial Interests, Personal, Stocks/Shares: BMS, MSD, AstraZeneca, bicycle; Financial Interests, Institutional, Steering Committee Member: BMS, Novartis; Financial Interests, Institutional, Research Grant: Ipsen, MSD, Pfizer, BMS; Financial Interests, Personal and Institutional, Steering Committee Member: EISAI, Ipsen; Non-Financial Interests, Member: ASCO, German medical Oncology and Hematology Society; Non-Financial Interests, Advisory Role: German Cancer Society; Non-Financial Interests, Leadership Role: Working Group medical oncology; Other, Travel support to ESMO 2022: Pfizer; Other, Travel support for meeting: Merck Serono; Other, Travel Support ASCO GU 2024: Ipsen; Other, Travel Support: Janssen Cilag. T. Telli: Financial Interests, Personal, Speaker, Consultant, Advisor: Abx. C. Kesch: Financial Interests, Personal, Stocks/Shares: Sustained Therapeutics, Telix, BioNTech, Actinium Pharmaceuticals, Formycon, UroGen pharma, Chimerix, Teladoc; Financial Interests, Personal, Research Funding: AAA/Novartis, Mariana, Amgen. P. Meyer: Financial Interests, Institutional, Speaker’s Bureau: Siemens Healthineers AG. K. Rahbar: Financial Interests, Personal, Speaker, Consultant, Advisor: AAA/Novartis, Bayer, Abx, UroTrials, Pharmtrace. K. Herrmann: Financial Interests, Personal, Advisory Board: Bayer, Adacap/Novartis, Curium, Boston Scientific, GE Healthcare, AstraZeneca; Financial Interests, Personal, Invited Speaker: Sirtex, Siemens Healthineers, Monrol; Financial Interests, Personal, Other, Consultant: Amgen; Financial Interests, Personal, Other, DMSB: Y-mAbs; Financial Interests, Personal, Advisory Board, Scientific Advisor: AdvanceCell; Financial Interests, Personal, Advisory Board, Advisor, Consultant: Janssen; Financial Interests, Personal, Advisory Board, Consultant: Eco1R, Fusion Pharmaceuticals, Genentech; Financial Interests, Personal, Member of Board of Directors: Sofie Biosciences, Pharma 15; Financial Interests, Personal, Ownership Interest: Sofie Biosciences; Financial Interests, Personal, Stocks/Shares: Aktis Oncology, AdvanCell, Convergent Therapeutics; Non-Financial Interests, Leadership Role, Chair Oncology&Theragnostics Committee: EANM. B.A. Hadaschik: Financial Interests, Personal, Advisory Board: Janssen, Bayer, ABX, Lightpoint Medical, Amgen, MSD, Pfizer, Novartis; Financial Interests, Personal, Invited Speaker: Astellas, Monrol; Financial Interests, Institutional, Royalties: Uromed; Financial Interests, Personal and Institutional, Steering Committee Member: Janssen R&D; Financial Interests, Institutional, Funding: AAA/Novartis, BMS, German Research Foundation; Non-Financial Interests, Advisory Role, Working group member: German Cancer Aid; Non-Financial Interests, Leadership Role, Speaker prostate cancer working group: DKG AUO. All other authors have declared no conflicts of interest.