PSMA-Hybridbildgebung in der Diagnostik des Prostatakarzinoms – aktuelle Anwendungen und Perspektiven

Zusammenfassung

Hintergrund Das Prostatakarzinom (PCa) ist das häufigste Malignom des Mannes und die zweithäufigste krebsbedingte Todesursache der männlichen Bevölkerung in Deutschland. Die Bildgebung des prostataspezifischen Membranantigens (PSMA) mittels Hybridverfahren wie der Positronen-Emissions-Tomografie (PET) in Kombination mit der CT oder MRT stellt eine vergleichsweise neue Methode dar, die in den letzten Jahren zunehmend an Bedeutung in der Diagnostik des PCa gewonnen hat.

Methode Aktuelle Anwendungen der PSMA-Hybridbildgebung wurden basierend auf den deutschen und europäischen Leitlinien zum Thema Prostatakarzinom erörtert und um neue Entwicklungen basierend auf einer Literaturrecherche in PubMed aus 10/22 ergänzt.

Ergebnisse Die PSMA-PET/CT weist sowohl im Primärstaging von Hochrisikoprostatakarzinomen als auch beim Rezidiv nach Primärtherapie höhere Detektionsraten von Metastasen als die etablierten Methoden (CT, MRT und Skelettszintigrafie) auf. Trotz vielversprechender Ergebnisse prospektiver Studien in beiden Szenarien und dem deutlichen Einfluss der PSMA-PET auf Therapieentscheidungen liegen aktuell noch keine Analysen bezüglich ihres Einflusses auf das PCa-spezifische Überleben und das Gesamtüberleben vor. Daher wird in den meisten Situationen eine „kann“-Empfehlung für die PSMA-PET/CT ausgesprochen. Neue Behandlungsstrategien wie die metastasengerichtete Therapie oder die PSMA-Radioligandentherapie erweitern jedoch bereits jetzt schon den Einsatzbereich der PSMA-PET und verankern sie weiter im klinischen Alltag.

Schlussfolgerung Die PSMA-Hybridbildgebung stellt in verschiedenen Stadien des PCa die sensitivste Staging-Methode dar und ermöglicht damit die Entwicklung neuer Behandlungskonzepte. Prospektive Analysen sind jedoch notwendig, um ihren Einfluss auf das Patientenüberleben zu evaluieren.

Kernaussagen 

• Die PSMA-PET/CT ist der konventionellen Bildgebung beim Staging von Hochrisikoprostatakarzinomen überlegen.

• Im biochemischen Rezidiv kann die PSMA-Hybridbildgebung bereits bei niedrigen PSA-Werten Filiae erkennen.

• Therapieentscheidungen werden häufig durch Erkenntnisse aus der PSMA-PET/CT beeinflusst.

Zitierweise

• Koehler D, Berliner C, Shenas F et al. PSMA hybrid imaging in prostate cancer – current applications and perspectives. Fortschr Röntgenstr 2023; 195: 1001 – 1008

Key words

prostate - PET-CT - metastases - PET - staging

Publikationsverlauf

Eingereicht: 24. November 2022

Angenommen: 28. April 2023

Artikel online veröffentlicht:
22. Juni 2023

• References

• 1 Robert Koch-Institut und die Gesellschaft der epidemiologischen Krebsregister in Deutschland e. V. Krebs in Deutschland für 2017/2018. 13. Ausgabe. Berlin,. 2021
• 2 Zaorsky NG, Churilla TM, Egleston BL. et al. Causes of death among cancer patients. Ann Oncol 2017; 28: 400-407
• 3 Horoszewicz JS, Kawinski E, Murphy GP. Monoclonal antibodies to a new antigenic marker in epithelial prostatic cells and serum of prostatic cancer patients. Anticancer Res 1987; 7: 927-935
• 4 Yao V, Berkman CE, Choi JK. et al. Expression of prostate-specific membrane antigen (PSMA), increases cell folate uptake and proliferation and suggests a novel role for PSMA in the uptake of the non-polyglutamated folate, folic acid. Prostate 2010; 70: 305-316
• 5 Minner S, Wittmer C, Graefen M. et al. High level PSMA expression is associated with early psa recurrence in surgically treated prostate cancer. Prostate 2011; 71: 281-288
• 6 Hupe MC, Philippi C, Roth D. et al. Expression of prostate-specific membrane antigen (PSMA) on biopsies is an independent risk stratifier of prostate cancer patients at time of initial diagnosis. Front Oncol 2018; 8: 623
• 7 Trover JK, Beckett MLou, Wright GL. Detection and characterization of the prostate‐specific membrane antigen (PSMA) in tissue extracts and body fluids. Int J Cancer 1995; 62: 552-558
• 8 Silver D, Pellicer I, Fair W. et al. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res 1997; 3: 81-85
• 9 De Galiza BarbosaF, Queiroz MA, Nunes RF. et al. Nonprostatic diseases on PSMA PET imaging: A spectrum of benign and malignant findings. Cancer Imaging 2020; 20: 23
• 10 Rischpler C, Beck TI, Okamoto S. et al. 68Ga-PSMA-HBED-CC Uptake in Cervical, Celiac, and Sacral Ganglia as an Important Pitfall in Prostate Cancer PET Imaging. J Nucl Med 2018; 59: 1406-1411
• 11 Alberts I, Sachpekidis C, Dijkstra L. et al. The role of additional late PSMA-ligand PET/CT in the differentiation between lymph node metastases and ganglia. Eur J Nucl Med Mol Imaging 2020; 47: 642-651
• 12 Debnath S, Zhou N, McLaughlin M. et al. PSMA-Targeting Imaging and Theranostic Agents—Current Status and Future Perspective. Int J Mol Sci 2022; 23: 1158
• 13 Afshar-Oromieh A, Malcher A, Eder M. et al. 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; 40: 486-495
• 14 Oh SW, Wurzer A, Teoh EJ. et al. Quantitative and Qualitative Analyses of Biodistribution and PET Image Quality of a Novel Radiohybrid PSMA, 18F-rhPSMA-7, in Patients with Prostate Cancer. J Nucl Med 2020; 61: 702-709
• 15 Beheshti M, Manafi-Farid R, Geinitz H. et al. Multiphasic 68Ga-PSMA PET/CT in the detection of early recurrence in prostate cancer patients with a PSA level of less than 1 ng/mL: A prospective study of 135 patients. J Nucl Med 2020; 61: 1484-1490
• 16 Alberts I, Niklas-Hünermund J, Sachpekidis C. et al. Combination of Forced Diuresis with Additional Late Imaging in 68Ga-PSMA-11 PET/CT: Effects on Lesion Visibility and Radiotracer Uptake. J Nucl Med 2021; 62: 1252-1257
• 17 Giesel FL, Hadaschik B, Cardinale J. et al. 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; 44: 678-688
• 18 Giesel FL, Knorr K, Spohn F. 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: 362-368
• 19 Rauscher I, Krönke M, König M. et al. Matched-pair comparison of 68Ga-PSMA-11 PET/CT and 18F-PSMA-1007 PET/CT: Frequency of pitfalls and detection efficacy in biochemical recurrence after radical prostatectomy. J Nucl Med 2020; 61: 51-57
• 20 Alberts I, Seide SE, Mingels C. et al. Comparing the diagnostic performance of radiotracers in prostate cancer biochemical recurrence: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging 2022; 48: 2978-2989
• 21 Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF): S3-Leitlinie Prostatakarzinom, Langversion 6.0, 2021, AWMF Registernummer: 043/022OL. http://www.leitlinienprogramm-onkologie.de/leitlinien/prostatakarzinom
• 22 EAU Guidelines. Edn. presented at the EAU Annual Congress Amsterdam 2022. https://uroweb.org/guideline/prostate-cancer
• 23 Hofman MS, Lawrentschuk N, Francis RJ. et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study. Lancet 2020; 395: 1208-1216
• 24 Anttinen M, Ettala O, Malaspina S. et al. A Prospective Comparison of 18F-prostate-specific Membrane Antigen-1007 Positron Emission Tomography Computed Tomography, Whole-body 1.5 T Magnetic Resonance Imaging with Diffusion-weighted Imaging, and Single-photon Emission Computed Tomography/Computed. Eur Urol Oncol 2021; 4: 635-644
• 25 Hope TA, Eiber M, Armstrong WR. et al. Diagnostic Accuracy of 68Ga-PSMA-11 PET for Pelvic Nodal Metastasis Detection Prior to Radical Prostatectomy and Pelvic Lymph Node Dissection: A Multicenter Prospective Phase 3 Imaging Trial. JAMA Oncol 2021; 7: 1635-1642
• 26 Pienta KJ, Gorin MA, Rowe SP. et al. A Phase 2/3 Prospective Multicenter Study of the Diagnostic Accuracy of Prostate Specific Membrane Antigen PET/CT with 18F-DCFPyL in Prostate Cancer Patients (OSPREY). J Urol 2021; 206: 52-61
• 27 Zelefsky MJ, Fuks Z, Hunt M. et al. High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer. J Urol 2001; 166: 876-881
• 28 Freedland SJ, Humphreys EB, Mangold La. et al. Risk of Prostate Cancer – Specific Mortality Following Biochemical Recurrence After Radical Prostatectomy. JAMA 2005; 294: 433-439
• 29 Beresford MJ, Gillatt D, Benson RJ. et al. A systematic review of the role of imaging before salvage radiotherapy for post-prostatectomy biochemical recurrence. Clin Oncol 2010; 22: 46-55
• 30 Zhao G, Ji B. Head-To-Head Comparison of 68Ga-PSMA-11 PET/CT and 99mTc-MDP Bone Scintigraphy for the Detection of Bone Metastases in Patients with Prostate Cancer: A Meta-Analysis. Am J Roentgenol 2022; 219: 386-395
• 31 Perera M, Papa N, Roberts M. et al. 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-. Eur Urol 2020; 77: 403-417
• 32 Fendler WP, Calais J, Eiber M. et al. Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Single-Arm Clinical Trial. JAMA Oncol 2019; 5: 856-863
• 33 Cerci JJ, Fanti S, Lobato EE. et al. Diagnostic Performance and Clinical Impact of 68Ga-PSMA-11 PET/CT Imaging in Early Relapsed Prostate Cancer after Radical Therapy: A Prospective Multicenter Study (IAEA-PSMA Study). J Nucl Med 2022; 63: 240-247
• 34 Fendler WP, Ferdinandus J, Czernin J. et al. Impact of 68Ga-PSMA-11 PET on the management of recurrent prostate cancer in a prospective single-arm clinical trial. J Nucl Med 2020; 61: 1793-1799
• 35 Deandreis D, Guarneri A, Ceci F. et al. 68Ga-PSMA-11 PET/CT in recurrent hormone-sensitive prostate cancer (HSPC): a prospective single-centre study in patients eligible for salvage therapy. Eur J Nucl Med Mol Imaging 2020; 47: 2804-2815
• 36 Steuber T, Jilg C, Tennstedt P. et al. Standard of Care Versus Metastases-directed Therapy for PET-detected Nodal Oligorecurrent Prostate Cancer Following Multimodality Treatment: A Multi-institutional Case-control Study. Eur Urol Focus 2019; 5: 1007-1013
• 37 Phillips R, Shi WY, Deek M. et al. Outcomes of Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer: The ORIOLE Phase 2 Randomized Clinical Trial. JAMA Oncol 2020; 6: 650-659
• 38 Knipper S, Mehdi IraiM, Rauscher I. et al. Cohort Study of Oligorecurrent Prostate Cancer Patients: Oncological Outcomes of Patients Treated with Salvage Lymph Node Dissection via Prostate-specific Membrane Antigen-radioguided Surgery. Eur Urol 2022;
• 39 Rahbar K, Ahmadzadehfar H, Kratochwil C. et al. German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients. J Nucl Med 2017; 58: 85-90
• 40 Heck MM, Tauber R, Schwaiger S. et al. Treatment Outcome, Toxicity, and Predictive Factors for Radioligand Therapy with 177Lu-PSMA-I&T in Metastatic Castration-resistant Prostate Cancer. Eur Urol 2019; 75: 920-926
• 41 European Medicines Agency. Pluvicto. Lutetium (177Lu) vipivotide tetraxetan. Im Internet (Stand: 21.01.2023): https://www.ema.europa.eu/en/medicines/human/EPAR/pluvicto
• 42 Kratochwil C, Fendler WP, Eiber M. et al. EANM procedure guidelines for radionuclide therapy with 177 Lu-labelled PSMA-ligands (177 Lu-PSMA-RLT). Eur J Nucl Med Mol Imaging 2019; 46: 2536-2544
• 43 Sartor O, de Bono J, Chi KN. et al. Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med 2021; 385: 1091-1103
• 44 Hofman MS, Emmett L, Sandhu S. et al. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet 2021; 397: 797-804
• 45 Ferraro DA, Rüschoff JH, Muehlematter UJ. et al. Immunohistochemical PSMA expression patterns of primary prostate cancer tissue are associated with the detection rate of biochemical recurrence with 68Ga-PSMA-11-PET. Theranostics 2020; 10: 6082-6094
• 46 Rüschoff JH, Ferraro DA, Muehlematter UJ. et al. What’s behind 68Ga-PSMA-11 uptake in primary prostate cancer PET? Investigation of histopathological parameters and immunohistochemical PSMA expression patterns. Eur J Nucl Med Mol Imaging 2021; 48: 4042-4053
• 47 Vaz S, Hadaschik B, Gabriel M. et al. Influence of androgen deprivation therapy on PSMA expression and PSMA-ligand PET imaging of prostate cancer patients. Eur J Nucl Med Mol Imaging 2020; 47: 9-15
• 48 Aggarwal R, Wei X, Kim W. et al. Heterogeneous Flare in Prostate-specific Membrane Antigen Positron Emission Tomography Tracer Uptake with Initiation of Androgen Pathway Blockade in Metastatic Prostate Cancer. Eur Urol Oncol 2018; 1: 78-82
• 49 Emmett L, Yin C, Crumbaker M. et al. Rapid modulation of PSMA expression by androgen deprivation: Serial 68Ga-PSMA-11 PET in men with hormone-sensitive and castrate-resistant prostate cancer commencing androgen blockade. J Nucl Med 2019; 60: 950-954
• 50 Afshar-Oromieh A, Debus N, Uhrig M. et al. Impact of long-term androgen deprivation therapy on PSMA ligand PET/CT in patients with castration-sensitive prostate cancer. Eur J Nucl Med Mol Imaging 2018; 45: 2045-2054
• 51 Fanti S, Goffin K, Hadaschik BA. et al. Consensus statements on PSMA PET/CT response assessment criteria in prostate cancer. Eur J Nucl Med Mol Imaging 2021; 48: 469-476