COMBINED PSMA-PET/CT AND MRI STAGING IN INTERMEDIATE AND HIGH-RISK PATIENTS PROSTATA-CANCER (COMBINE-P)

This retrospective, multicentre comparative analysis aims to evaluate a new staging method for i) improved detection of intraprostatic index lesions, ii) local T-staging and iii) lymph node (LN) staging in men with clinically significant prostate cancer (csPCa) at intermediate/high risk by combining prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging using different tracers ((18)F) DCFPyL, Gallium-68, Fluor-18) and multiparametric magnetic resonance imaging (MRI) in patients with prostate cancer (PCa) who subsequently underwent radical prostatectomy (RP). Another secondary endpoint will be the additional value of PSMA-PET/CT in men with unremarkable MRI. Men at intermediate risk (PSA \> 10 ng/ml to 20 ng/ml or Gleason score 7 or cT category 2b) or high risk (PSA \> 20 ng/ml or Gleason score ≥ 8 or cT category 2c) who underwent PSMA-PET/CT and mpMRI followed by RP will be analysed in three different subgroups corresponding to the modalities i) PSMA-PET/CT with 18-F-DCFPyL (subgroup/arm A), ii) Gallium-68 PSMA-PET/CT (subgroup/arm B) and Fluorine-18 PSMA-PET/CT (subgroup/arm C). The validation of the accuracy of the detection of intraprostatic index lesions, local and lymph node staging by MRI and PSMA-PET-CT with different tracers is carried out using the histological radical prostatectomy specimens. In addition, the prediction of the International Society of Urolgenital Pathology (ISUP) graduation group (GG) within intraprostatic index lesions will be determined using the SUV (standardised uptake value) in PSMA-PET-CT and using ADC values (Apparent Diffusion Coefficient of the diffusion-weighted MRI sequence) in MRI (7,8). The ability of PSMA-PET-CT to predict extraprostatic, i.e. capsule-transcending, tumour growth is also analysed in comparison with MRI. In addition, the correlation of tumour localisation (right vs. left) in relation to positive lymph nodes (right vs. left) is analysed. Finally, the added value of PSMAPET-CT in the case of negative, unsuspicious MRI is determined. Overall, our analysis aims to improve patient care by analysing the potential of non-invasive "digital biopsy" in terms of lesion detection and prediction of the histological grading group. In addition, a proof-of-concept for personalised lymph node dissection based on prediction of lymph node metastasis and patient-tailored nerve sparing with accurate prediction of extracapsular extension will be tested based on combined preoperative PSMA-PET and MRI imaging. The results of these two analyses will have a direct impact on clinical practice and the further use of highly specialised imaging. In addition, this multi-centre data analysis will provide the European Prostate Cancer Center of Excellence (EPCCE) group with a proof-of-concept for future projects.

Sex

Male

Minimum age

45 Years

Maximum age

80 Years

Inclusion Criteria:

1. Men aged from 45 to 80 years
2. Men with intermediate risk or high risk csPCa
3. Men who underwent RP
4. Men who underwent multiparametric MRI and PSMA-PET/CT before RP

Exclusion Criteria:

a) Men with known prostate cancer, who did not underwent RP and who did not underwent MRI or PSMA-PET-CT

• BACKGROUNDPerera M, Papa N, Christidis D, Wetherell D, Hofman MS, Murphy DG, Bolton D, Lawrentschuk N. Sensitivity, Specificity, and Predictors of Positive 68Ga-Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer: A Systematic Review and Meta-analysis. Eur Urol. 2016 Dec;70(6):926-937. doi: 10.1016/j.eururo.2016.06.021. Epub 2016 Jun 28. PMID 27363387
• BACKGROUNDPerera M, Papa N, Roberts M, Williams M, Udovicich C, Vela I, Christidis D, Bolton D, Hofman MS, Lawrentschuk N, Murphy DG. Gallium-68 Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer-Updated Diagnostic Utility, Sensitivity, Specificity, and Distribution of Prostate-specific Membrane Antigen-avid Lesions: A Systematic Review and Meta-analysis. Eur Urol. 2020 Apr;77(4):403-417. doi: 10.1016/j.eururo.2019.01.049. Epub 2019 Feb 14. PMID 30773328
• BACKGROUNDMazzone E, Cannoletta D, Quarta L, Chen DC, Thomson A, Barletta F, Stabile A, Moon D, Eapen R, Lawrentschuk N, Montorsi F, Siva S, Hofman MS, Chiti A, Murphy DG, Briganti A, Perera ML. A Comprehensive Systematic Review and Meta-analysis of the Role of Prostate-specific Membrane Antigen Positron Emission Tomography for Prostate Cancer Diagnosis and Primary Staging before Definitive Treatment. Eur Urol. 2025 Jun;87(6):654-671. doi: 10.1016/j.eururo.2025.03.003. Epub 2025 Mar 27. PMID 40155242
• BACKGROUNDKoerber SA, Utzinger MT, Kratochwil C, Kesch C, Haefner MF, Katayama S, Mier W, Iagaru AH, Herfarth K, Haberkorn U, Debus J, Giesel FL. 68Ga-PSMA-11 PET/CT in Newly Diagnosed Carcinoma of the Prostate: Correlation of Intraprostatic PSMA Uptake with Several Clinical Parameters. J Nucl Med. 2017 Dec;58(12):1943-1948. doi: 10.2967/jnumed.117.190314. Epub 2017 Jun 15. PMID 28619734
• BACKGROUNDRowe SP, Campbell SP, Mana-Ay M, Szabo Z, Allaf ME, Pienta KJ, Pomper MG, Ross AE, Gorin MA. Prospective Evaluation of PSMA-Targeted 18F-DCFPyL PET/CT in Men with Biochemical Failure After Radical Prostatectomy for Prostate Cancer. J Nucl Med. 2020 Jan;61(1):58-61. doi: 10.2967/jnumed.119.226514. Epub 2019 Jun 14.