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

NCT07455097 | Active Not Recruiting DMC

• 2 other identifiers: UKD-26-001COMBINE-P
• Study Type: observational
• Target: 600
• Locations: 7 countries
• Sites: 10

Brief Summary

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.

Conditions

Intermediate-risk Prostate Cancer; High-risk Prostate Cancer

Keywords

Prostate Cancer; PSMA-PET/CT; Radical Prostatectomy; Intermediate-risk Prostate Cancer; High-risk Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• The primary outcome includes the correct LN-staging after radical prostatectomy with the use of PSMA-PET-CT with different tracers and mpMRI in patients with significant prostate cancer (ISUP grade group ≥ 2) of intermediate- or high-risk group

  The primary outcome includes the correct LN-staging after radical prostatectomy with the use of PSMA-PET-CT with different tracers and mpMRI in patients with significant prostate cancer (ISUP grade group ≥ 2) of intermediate- or high-risk group

  01.01.2026-31.12.2026

Secondary Outcomes (3)

• • ISUP GG prediction by SUV (standardized uptake value) and ADC (apparent diffusion coefficient) values on mpMRI

  01.12.2026-31.12.2026

• Extraprostatic disease

  01.12.2026-31.12.2026

• Significant prostate cancer detection by one modality

  01.12.2026-31.12.2026

Study Arms (1)

Patients staged with PSMA-PET/CT of several tracers prior to Radical Prostatectomy

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)

Diagnostic Test: PSMA-11

Interventions

PSMA-11 DIAGNOSTIC_TEST

PSMA-PET/CT using 68Gallium or 18Fluor or 18DCFPyl as staging prior to Radical Prostatectomy

Patients staged with PSMA-PET/CT of several tracers prior to Radical Prostatectomy

Eligibility Criteria

• Age: 45 Years - 80 Years
• Gender Eligibility Details: Male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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 and subsequentially RP will be analyzed in three different subgroups, assigned to the modalities they underwent in staging in addition to MRI: i) PSMA-PET/CT using 18-F-DCFPyL (subgroup/arm A), ii) PSMA-PET/CT using Gallium-68 (subgroup/arm B) and PSMA-PET/CT using Fluorine-18 (subgroup/arm C). Validation of the accuracy of intraprostatic lesion detection, local staging and of LN-Staging by MRI or PSMA-PET/CT with different tracers is confirmed after radical prostatectomy.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Heinrich-Heine University, Duesseldorf: lead
• Marienhospital Herne: collaborator
• San Raffaele University Hospital, Italy: collaborator
• Lund University Hospital: collaborator
• KU Leuven: collaborator
• Fortis Hospital, India: collaborator
• University of Bern: collaborator
• Erasmus Medical Center: collaborator
• Universität Tübingen: collaborator
• Medical University of Vienna: collaborator
• European Association of Urology Research Foundation: collaborator
• University Hospital, Paris: collaborator
• Ludwig-Maximilians - University of Munich: collaborator

Study Sites (10)

Medical University Vienna

Vienna, Austria

Location

KU Leuven

Leuven, Belgium

Location

University Hospital Düsseldorf

Düsseldorf, 40225, Germany

Location

Marienhospital Herne

Herne, Germany

Location

Ludwig-Maximilians-University Munich

Munich, Germany

Location

University Hospital Tübingen

Tübingen, Germany

Location

Fortis Hospital

Kolkata, India

Location

San Raffaele University Hospital Milan

Milan, Italy

Location

Lund University Hospital

Lund, Sweden

Location

University Hospital Bern

Bern, Switzerland

Location

Related Publications (9)

• Perera 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 BACKGROUND

• Perera 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 BACKGROUND

• Mazzone 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 BACKGROUND

• Koerber 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 BACKGROUND

• Rowe 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.

  PMID: 31201249 BACKGROUND

• Giesel FL, Hadaschik B, Cardinale J, Radtke J, Vinsensia M, Lehnert W, Kesch C, Tolstov Y, Singer S, Grabe N, Duensing S, Schafer M, Neels OC, Mier W, Haberkorn U, Kopka K, Kratochwil C. F-18 labelled PSMA-1007: biodistribution, radiation dosimetry and histopathological validation of tumor lesions in prostate cancer patients. Eur J Nucl Med Mol Imaging. 2017 Apr;44(4):678-688. doi: 10.1007/s00259-016-3573-4. Epub 2016 Nov 26.

  PMID: 27889802 BACKGROUND

• Afshar-Oromieh A, Babich JW, Kratochwil C, Giesel FL, Eisenhut M, Kopka K, Haberkorn U. The Rise of PSMA Ligands for Diagnosis and Therapy of Prostate Cancer. J Nucl Med. 2016 Oct;57(Suppl 3):79S-89S. doi: 10.2967/jnumed.115.170720.

  PMID: 27694178 BACKGROUND

• Afshar-Oromieh A, Malcher A, Eder M, Eisenhut M, Linhart HG, Hadaschik BA, Holland-Letz T, Giesel FL, Kratochwil C, Haufe S, Haberkorn U, Zechmann CM. PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging. 2013 Apr;40(4):486-95. doi: 10.1007/s00259-012-2298-2. Epub 2012 Nov 24.

  PMID: 23179945 BACKGROUND

• Afshar-Oromieh A, Haberkorn U, Eder M, Eisenhut M, Zechmann CM. [68Ga]Gallium-labelled PSMA ligand as superior PET tracer for the diagnosis of prostate cancer: comparison with 18F-FECH. Eur J Nucl Med Mol Imaging. 2012 Jun;39(6):1085-6. doi: 10.1007/s00259-012-2069-0. Epub 2012 Feb 4. No abstract available.

  PMID: 22310854 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Jan Philipp Radtke, Professor Dr. med.

  Heinrich-Heine University, Duesseldorf

  STUDY CHAIR

• Isabelle Busshoff, Dr. med.

  Heinrich-Heine University, Duesseldorf

  PRINCIPAL INVESTIGATOR

• Peter Albers, Professor Dr. med.

  Heinrich-Heine University, Duesseldorf

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2026
• First Posted: March 6, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); IN (1); DE (4); AU (1); IT (1); SE (1); CH (1)