A randomised, prospective and head-to-head comparison of [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 for the detection of recurrent prostate cancer in PSMA-ligand PET/CT-Protocol design and rationale

Ian Alberts, Lukas Bütikofer, Axel Rominger, Ali Afshar-Oromieh, Ian Alberts, Lukas Bütikofer, Axel Rominger, Ali Afshar-Oromieh

Abstract

Background: A number of radiopharmaceuticals are available for the detection of recurrent prostate cancer (rPC), but few comparative imaging trials have been performed comparing them. In particular, there are no prospective head-to-head comparisons of the recently introduced [18F]PSMA-1007 to the existing standard of care [68Ga]Ga-PSMA-11. The purpose of this trial is to establish the non-inferiority of the new radiopharmaceutical in terms of the rate of PET-positive findings and to obtain an intra-individual comparison of accuracy and radiopharmaceutical kinetics.

Methods: In this cross-over trial we will randomise 100 individuals to receive either first a standard-of-care PET/CT using [68Ga]Ga-PSMA-11 followed by an additional [18F]PSMA-1007 PET/CT within 2 weeks, or vice-versa. Inclusion criteria include patients 18 years and older with biochemical recurrence of prostate cancer following radical prostatectomy, defined as two consecutive prostate specific antigen (PSA) levels > 0.2 ng/ml. Detection rate at the patient-based level is the primary end-point. Each scan will be interpreted by a panel of six independent and masked readers (three for [68Ga]Ga-PSMA-11 and three for [18F]PSMA-1007) which consensus majority in cases of discrepancy. To confirm the PET-positivity rate at a patient based level, follow up at 6 months following the first scan will be performed to a composite standard of truth. Secondary endpoints shall include an intra-individual comparison of radiopharmaceutical-kinetics, per-region detection rate and positive predictive value.

Discussion: This is the first randomised prospective comparative imaging trial to compare the established [68Ga]Ga-PSMA-11 with [18F]PSMA-1007 and will determine whether the new radiopharmaceutical is non-inferior to the established standard-of-care in terms of patient-level detection rate.

Clinical trial registration: Registered with and approved by the regional ethics authority #2020-02903 (submitted 09.12.2020, approval 16.12.2021) and the regulatory authority SwissMedic 2020DR2103. Registered with ClinicalTrials.gov Identifier NCT05079828 and additionally in a national language in the Swiss National Clinical Trials Portal (SNCTP).

Conflict of interest statement

The authors have declared that no competing interests exis.

Figures

Fig 1. SPRIT schedule.
Fig 1. SPRIT schedule.
Fig 2. CONSORT study flow diagram.
Fig 2. CONSORT study flow diagram.
Fig 3. Study flow chart detailing consent…
Fig 3. Study flow chart detailing consent procedures.
Fig 4. Example interpretation criteria for patients…
Fig 4. Example interpretation criteria for patients undergoing biopsy or radiotherapy (with and without systemic hormone deprivation therapy) image adapted from Emmett et al. [20].

References

    1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71:7–33. doi: 10.3322/caac.21654
    1. Stefan AK, Katharina S, Clemens K, Erik W, Matthias FH, Sonja K, et al.. Clinical outcome of PSMA-guided radiotherapy for patients with oligorecurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2021;48:143–51. doi: 10.1007/s00259-020-04777-z
    1. Calais J, Ceci F, Eiber M, Hope TA, Hofman MS, Rischpler C, et al.. (18)F-fluciclovine PET-CT and (68)Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, single-arm, comparative imaging trial. Lancet Oncol. 2019;20:1286–94. doi: 10.1016/S1470-2045(19)30415-2
    1. Alberts I, Mingels C, Zacho HD, Lanz S, Schoder H, Rominger A, et al.. Comparing the clinical performance and cost efficacy of [(68)Ga]Ga-PSMA-11 and [(18)F]PSMA-1007 in the diagnosis of recurrent prostate cancer: a Markov chain decision analysis. Eur J Nucl Med Mol Imaging. 2021. doi: 10.1007/s00259-021-05620-9
    1. Werner RA, Derlin T, Lapa C, Sheikbahaei S, Higuchi T, Giesel FL, et al.. (18)F-Labeled, PSMA-Targeted Radiopharmaceuticals: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging. Theranostics. 2020;10:1–16. doi: 10.7150/thno.37894
    1. Alberts I, Huenermund JN, Sachpekidis C, Zacho HD, Mingels C, Dijkstra L, et al.. Combination of forced diuresis with additional late imaging in 68Ga-PSMA-11 PET/CT—effects on lesion visibility and radiopharmaceutical uptake. Journal of Nuclear Medicine. 2021:jnumed.120.257741. doi: 10.2967/jnumed.120.257741
    1. Alberts I, Prenosil G, Mingels C, Bohn KP, Viscione M, Sari H, et al.. Feasibility of late acquisition [68Ga]Ga-PSMA-11 PET/CT using a long axial field-of-view PET/CT scanner for the diagnosis of recurrent prostate cancer-first clinical experiences. Eur J Nucl Med Mol Imaging. 2021;48:4456–62. doi: 10.1007/s00259-021-05438-5
    1. Alberts IL, Seide SE, Mingels C, Bohn KP, Shi K, Zacho HD, et al.. Comparing the diagnostic performance of radiopharmaceuticals in recurrent prostate cancer: a systematic review and network meta-analysis. Eur J Nucl Med Mol Imaging. 2021;48:2978–89. doi: 10.1007/s00259-021-05210-9
    1. Fendler WP, Calais J, Eiber M, Flavell RR, Mishoe A, Feng FY, et al.. Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Single-Arm Clinical Trial. JAMA Oncol. 2019;5:856–63. doi: 10.1001/jamaoncol.2019.0096
    1. Mingels C, Bohn KP, Rominger A, Afshar-Oromieh A, Alberts I. Diagnostic accuracy of [(18)F]PSMA-1007 PET/CT in biochemical recurrence of prostate cancer. Eur J Nucl Med Mol Imaging. 2022. doi: 10.1007/s00259-022-05693-0
    1. Grünig H, Maurer A, Thali Y, Kovacs Z, Strobel K, Burger IA, et al.. Focal unspecific bone uptake on [18F]-PSMA-1007 PET: a multicenter retrospective evaluation of the distribution, frequency, and quantitative parameters of a potential pitfall in prostate cancer imaging. European Journal of Nuclear Medicine and Molecular Imaging. 2021. doi: 10.1007/s00259-021-05424-x
    1. Ringheim A, Campos Neto GC, Anazodo U, Cui L, da Cunha ML, Vitor T, et al.. Kinetic modeling of (68)Ga-PSMA-11 and validation of simplified methods for quantification in primary prostate cancer patients. EJNMMI Res. 2020;10:12. doi: 10.1186/s13550-020-0594-6
    1. Sachpekidis C, Afshar-Oromieh A, Kopka K, Strauss DS, Pan L, Haberkorn U, et al.. (18)F-PSMA-1007 multiparametric, dynamic PET/CT in biochemical relapse and progression of prostate cancer. Eur J Nucl Med Mol Imaging. 2020;47:592–602. doi: 10.1007/s00259-019-04569-0
    1. Sari H, Mingels C, Alberts I, Hu J, Buesser D, Shah V, et al.. First results on kinetic modelling and parametric imaging of dynamic (18)F-FDG datasets from a long axial FOV PET scanner in oncological patients. Eur J Nucl Med Mol Imaging. 2022. doi: 10.1007/s00259-021-05623-6
    1. Haupt F, Dijkstra L, Alberts I, Sachpekidis C, Fech V, Boxler S, et al.. (68)Ga-PSMA-11 PET/CT in patients with recurrent prostate cancer-a modified protocol compared with the common protocol. Eur J Nucl Med Mol Imaging. 2019. doi: 10.1007/s00259-019-04548-5
    1. Rowe SP, Pienta KJ, Pomper MG, Gorin MA. PSMA-RADS Version 1.0: A Step Towards Standardizing the Interpretation and Reporting of PSMA-targeted PET Imaging Studies. European urology. 2018;73:485–7. doi: 10.1016/j.eururo.2017.10.027
    1. Calais J, Ceci F, Eiber M, Hope TA, Hofman MS, Rischpler C, et al.. 18F-fluciclovine PET-CT and 68Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, single-arm, comparative imaging trial. The Lancet Oncology. 2019;20:1286–94. doi: 10.1016/S1470-2045(19)30415-2
    1. Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, et al.. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2008;26:1148–59. doi: 10.1200/JCO.2007.12.4487
    1. Emmett L, Metser U, Bauman G, Hicks RJ, Weickhardt A, Davis ID, et al.. Prospective, Multisite, International Comparison of 18F-Fluoromethylcholine PET/CT, Multiparametric MRI, and 68Ga-HBED-CC PSMA-11 PET/CT in Men with High-Risk Features and Biochemical Failure After Radical Prostatectomy: Clinical Performance and Patient Outcomes. Journal of Nuclear Medicine. 2019;60:794–800 doi: 10.2967/jnumed.118.220103
    1. Rauscher I, Kronke M, Konig M, Gafita A, Maurer T, Horn T, et al.. Matched-pair comparison of (68)Ga-PSMA-11 and (18)F-PSMA-1007 PET/CT: frequency of pitfalls and detection efficacy in biochemical recurrence after radical prostatectomy. J Nucl Med. 2019. doi: 10.2967/jnumed.119.229187
    1. Kuten J, Fahoum I, Savin Z, Shamni O, Gitstein G, Hershkovitz D, et al.. Head- to head Comparison of (68)Ga-PSMA-11 with (18)F-PSMA-1007 PET/CT in Staging Prostate Cancer Using Histopathology and Immunohistochemical Analysis as Reference-Standard. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. 2019. doi: 10.2967/jnumed.119.234187
    1. Dietlein F, Kobe C, Hohberg M, Zlatopolskiy BD, Krapf P, Endepols H, et al.. Intraindividual comparison of 18F-PSMA-1007 with renally excreted PSMA ligands for PSMA-PET imaging in patients with relapsed prostate cancer. Journal of Nuclear Medicine. 2019. doi: 10.2967/jnumed.119.234898
    1. Afshar-Oromieh A, Hetzheim H, Kubler W, Kratochwil C, Giesel FL, Hope TA, et al.. Radiation dosimetry of (68)Ga-PSMA-11 (HBED-CC) and preliminary evaluation of optimal imaging timing. European journal of nuclear medicine and molecular imaging. 2016;43:1611–20. doi: 10.1007/s00259-016-3419-0
    1. Czarniecki M, Mena E, Lindenberg L, Cacko M, Harmon S, Radtke JP, et al.. Keeping up with the prostate-specific membrane antigens (PSMAs): an introduction to a new class of positron emission tomography (PET) imaging agents. Transl Androl Urol. 2018;7:831–43. doi: 10.21037/tau.2018.08.03
    1. Morris MJ, Rowe SP, Gorin MA, Saperstein L, Pouliot F, Josephson D, et al.. Diagnostic Performance of (18)F-DCFPyL-PET/CT in Men with Biochemically Recurrent Prostate Cancer: Results from the CONDOR Phase III, Multicenter Study. Clin Cancer Res. 2021;27:3674–82. doi: 10.1158/1078-0432.CCR-20-4573
    1. Witkowska-Patena E, Giżewska A, Dziuk M, Miśko J, Budzyńska A, Walęcka-Mazur A. Diagnostic performance of 18F-PSMA-1007 PET/CT in biochemically relapsed patients with prostate cancer with PSA levels ≤ 2.0 ng/ml. Prostate Cancer and Prostatic Diseases. 2020;23:343–8. doi: 10.1038/s41391-019-0194-6
    1. Rahbar K, Afshar-Oromieh A, Seifert R, Wagner S, Schafers M, Bogemann M, et al.. Diagnostic performance of (18)F-PSMA-1007 PET/CT in patients with biochemical recurrent prostate cancer. European journal of nuclear medicine and molecular imaging. 2018;45:2055–61. doi: 10.1007/s00259-018-4089-x
    1. Giesel FL, Knorr K, Spohn F, Will L, Maurer T, Flechsig P, et al.. Detection Efficacy of (18)F-PSMA-1007 PET/CT in 251 Patients with Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy. J Nucl Med. 2019;60:362–8. doi: 10.2967/jnumed.118.212233
    1. Giesel FL, Will L, Lawal I, Lengana T, Kratochwil C, Vorster M, et al.. Intraindividual Comparison of (18)F-PSMA-1007 and (18)F-DCFPyL PET/CT in the Prospective Evaluation of Patients with Newly Diagnosed Prostate Carcinoma: A Pilot Study. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. 2018;59:1076–80. doi: 10.2967/jnumed.117.204669

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