Einsatz von PSMA-PET/CT beim Prostatakarzinom

In den letzten Jahren hat die PSMA-Liganden-PET vielversprechende Ergebnisse gezeigt und so enorm an Bedeutung bei der Versorgung von Prostatakarzinompatienten gewonnen. Dieser Beitrag soll einen Überblick zur PSMA-PET/CT in unterschiedlichen klinischen Situationen geben und auf aktuelle prospektive Studienergebnisse eingehen, welche den Stellenwert der PSMA-vermittelten Hybridbildgebung in den kommenden Jahren noch weiter steigern werden.

Abstract

Prostate cancer is by far the most frequent malignant disease in men in Germany and the second most common cancer in men worldwide. Due to demographic trends both incidence and prevalence are expected to increase even more in the future. To provide patients with the most effective treatment a good stratification using precise imaging is essential. PSMA PET/CT has shown superiority over conventional imaging both in primary staging and biochemical recurrence of prostate cancer in initial single-institutional studies and subsequent larger prospective trials. The higher diagnostic accuracy already has a substantial impact on the clinical management of prostate cancer patients and, in case of recurrent prostate cancer, PSMA-PET/CT has been part of national and international guidelines for years. Since the introduction of the first Ga-68-labeld ligands, PSMA-tracer have undergone continuous development and improvement. Currently, fluorine-labeled compounds are gaining more and more importance due to advantages regarding imaging resolution, production and logistics for a higher number of patients. Currently, several international phase III trials are recruiting patients and aim for an approval of the new PSMA PET-tracer. This article is intended to provide an overview of PSMA-PET/CT in different clinical settings and to highlight results of recent studies, which will strengthen the significance of PSMA-targeting hybrid imaging in the next years.

Schlüsselwörter

biochemisches Rezidiv - PET - Prostatakarzinom - PSMA - Staging

Keywords

Biochemical recurrence - PET - prostate cancer - PSMA - staging

• Literatur

• 1 Robert Koch-Institut, Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V. Krebs in Deutschland 2015/2016 (12. Aufl). Berlin: Robert Koch-Institut; 2019: 98-101
• 2 Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF. Leitlinienprogramm Onkologie: Interdisziplinäre Leitlinie der Qualität S3 zur Früherkennung, Diagnose und Therapie der verschiedenen Stadien des Prostatakarzinoms, Langversion 5.0. 2018 Im Internet (Stand: 14.09.2020): http://www.leitlinienprogramm-onkologie.de/leitlinien/prostatakarzinom
• 3 Barnes B, Kraywinkel K, Nowossadeck E. et al. Bericht zum Krebsgeschehen in Deutschland 2016. Berlin: Robert Koch-Institut; 2016.
• 4 Torre LA, Siegel RL, Ward EM. et al. Global cancer incidence and mortality rates and trends – an update. Cancer epidemiology, biomarkers & prevention. The American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2016; 25: 16-27
• 5 Ferlay J, Ervik M, Lam F. Global cancer observatory: cancer today. Lyon, France: International Agency for Research on Cancer; 2018 Im Internet (Stand: 14.09.2020): https://gco.iarc.fr/today
• 6 Hövels AM, Heesakkers RA, Adang EM. et al. The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis. Clin Radiol 2008; 63: 387-395
• 7 Evangelista L, Guttilla A, Zattoni F. et al. Utility of choline positron emission tomography/computed tomography for lymph node involvement identification in intermediate- to high-risk prostate cancer: a systematic literature review and meta-analysis. Eur Urol 2013; 63: 1040-1048
• 8 Nanni C, Zanoni L, Pultrone C. et al. (18)F-FACBC (anti1-amino-3-(18)F-fluorocyclobutane-1-carboxylic acid) versus (11)C-choline PET/CT in prostate cancer relapse: results of a prospective trial. Eur J Nucl Med Mol Imaging 2016; 43: 1601-1610
• 9 Silver DA, Pellicer I, Fair WR. et al. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res 1997; 3: 81-85
• 10 Mannweiler S, Amersdorfer P, Trajanoski S. et al. Heterogeneity of prostate-specific membrane antigen (PSMA) expression in prostate carcinoma with distant metastasis. Pathol Oncol Res 2009; 15: 167-172
• 11 Bostwick DG, Pacelli A, Blute M. et al. Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases. Cancer 1998; 82: 2256-2261
• 12 Bander NH, Trabulsi EJ, Kostakoglu L. et al. Targeting metastatic prostate cancer with radiolabeled monoclonal antibody J591 to the extracellular domain of prostate specific membrane antigen. J Urol 2003; 170: 1717-1721
• 13 Ahn T, Roberts MJ, Abduljabar A. et al. A review of prostate-specific membrane antigen (PSMA) Positron emission tomography (PET) in renal cell carcinoma (RCC). Mol Imaging Biol 2019; 21: 799-807
• 14 Sasikumar A, Joy A, Nanabala R. et al. (68)Ga-PSMA PET/CT imaging in primary hepatocellular carcinoma. Eur J Nucl Med Mol Imaging 2016; 43: 795-796
• 15 Shetty D, Loh H, Bui C. et al. Elevated 68Ga Prostate-Specific Membrane Antigen Activity in Metastatic Non-Small Cell Lung Cancer. Clin Nucl Med 2016; 41: 414-416
• 16 Kanthan GL, Coyle L, Kneebone A. et al. follicular lymphoma showing avid uptake on 68Ga PSMA-HBED-CC PET/CT. Clin Nucl Med 2016; 41: 500-501
• 17 Haffner MC, Kronberger IE, Ross JS. et al. Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers. Hum Pathol 2009; 40: 1754-1761
• 18 Ghosh A, Heston WD. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J Cell Biochem 2004; 91: 528-539
• 19 Budäus L, Leyh-Bannurah SR, Salomon G. et al. Initial experience of (68)Ga-PSMA PET/CT imaging in high-risk prostate cancer patients prior to radical prostatectomy. Eur Urol 2016; 69: 393-396
• 20 Eder M, Schafer M, Bauder-Wust U. et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjugate Chem 2012; 23: 688-697
• 21 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
• 22 Maurer T, Eiber M, Schwaiger M. et al. Current use of PSMA-PET in prostate cancer management. Nat Rev Urol 2016; 13: 226-235
• 23 Rowe SP, Gorin MA, Allaf ME. et al. PET imaging of prostate-specific membrane antigen in prostate cancer: current state of the art and future challenges. Prostate Cancer prostatic Dis 2016; 19: 223-230
• 24 Kesch C, Kratochwil C, Mier W. et al. (68)Ga or (18)F for prostate cancer imaging?. J Nucl Med 2017; 58: 687-688
• 25 Eiber M, Weirich G, Holzapfel K. et al. Simultaneous (68)Ga-PSMA HBED-CC PET/MRI Improves the localization of primary prostate cancer. Eur Urol 2016; 70: 829-836
• 26 Giesel FL, Sterzing F, Schlemmer HP. et al. Intra-individual comparison of (68)Ga-PSMA-11-PET/CT and multi-parametric MR for imaging of primary prostate cancer. Eur J Nucl Med Mol Imaging 2016; 43: 1400-1406
• 27 Herlemann A, Wenter V, Kretschmer A. et al. (68)Ga-PSMA positron emission tomography/computed tomography provides accurate staging of lymph node regions prior to lymph node dissection in patients with prostate cancer. Eur Urol 2016; 70: 553-557
• 28 Pyka T, Okamoto S, Dahlbender M. et al. Comparison of bone scintigraphy and (68)Ga-PSMA PET for skeletal staging in prostate cancer. Eur J Nucl Med Mol Imaging 2016; 43: 2114-2121
• 29 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
• 30 Gorin MA, Rowe SP, Patel HD. et al. Prostate specific membrane antigen targeted (18)F-DCFPyL positron emission tomography/computerized tomography for the preoperative staging of high risk prostate cancer: results of a prospective, phase II, single center study. J Urol 2018; 199: 126-132
• 31 Kronke M, Wurzer A, Schwamborn K. et al. Histologically-confirmed diagnostic efficacy of (18)F-rhPSMA-7 positron emission tomography for N-staging of patients with primary high risk prostate cancer. J Nucl Med 2019;
• 32 Mottet N, Bellmunt J, Bolla M. et al. EAU-ESTRO-SIOG Guidelines on prostate cancer. Part 1: Screening, diagnosis, and local treatment with curative intent. Eur Urol 2017; 71: 618-629
• 33 Cornford P, Bellmunt J, Bolla M. et al. EAU-ESTRO-SIOG Guidelines on prostate cancer. Part II: Treatment of relapsing, metastatic, and castration-resistant prostate cancer. Eur Urol 2017; 71: 630-642
• 34 Vargas HA, Martin-Malburet AG, Takeda T. et al. Localizing sites of disease in patients with rising serum prostate-specific antigen up to 1 ng/ml following prostatectomy: How much information can conventional imaging provide?. Urol Oncol 2016; 34: 482.e485-482.e410
• 35 Afshar-Oromieh A, Avtzi E, Giesel FL. et al. The diagnostic value of PET/CT imaging with the (68)Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging 2015; 42: 197-209
• 36 Eiber M, Maurer T, Souvatzoglou M. et al. Evaluation of Hybrid ⁶⁸Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy. J Nucl Med 2015; 56: 668-674
• 37 Krause BJ, Souvatzoglou M, Tuncel M. et al. The detection rate of [11C]choline-PET/CT depends on the serum PSA-value in patients with biochemical recurrence of prostate cancer. Eur J Nucl Med Mol Imaging 2008; 35: 18-23
• 38 van Leeuwen PJ, Stricker P, Hruby G. et al. (68) Ga-PSMA has a high detection rate of prostate cancer recurrence outside the prostatic fossa in patients being considered for salvage radiation treatment. BJU international 2016; 117: 732-739
• 39 Morigi JJ, Stricker PD, van Leeuwen PJ. et al. Prospective comparison of 18F-fluoromethylcholine versus 68Ga-PSMA PET/CT in prostate cancer patients who have rising psa after curative treatment and are being considered for targeted therapy. J Nucl Med 2015; 56: 1185-1190
• 40 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;
• 41 Calais J, Ceci F, Eiber M. 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: 1286-1294
• 42 Giesel FL, Will L, Kesch C. et al. Biochemical recurrence of prostate cancer: initial results with [(18)F]PSMA-1007 PET/CT. J Nucl Med 2018; 59: 632-635
• 43 Afshar-Oromieh A, Holland-Letz T, Giesel FL. et al. Diagnostic performance of (68)Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients. Eur J Nucl Med Mol Imaging 2017; 44: 1258-1268
• 44 Fendler WP, Weber M, Iravani A. et al. Prostate-specific membrane antigen ligand positron emission tomography in men with nonmetastatic castration-resistant prostate cancer. Clin Cancer Res 2019; 25: 7448-7454
• 45 Dewes S, Schiller K, Sauter K. et al. Integration of (68)Ga-PSMA-PET imaging in planning of primary definitive radiotherapy in prostate cancer: a retrospective study. Radiat Oncol 2016; 11: 73
• 46 Sterzing F, Kratochwil C, Fiedler H. et al. (68)Ga-PSMA-11 PET/CT: a new technique with high potential for the radiotherapeutic management of prostate cancer patients. Eur J Nucl Med Mol Imaging 2016; 43: 34-41
• 47 von Eyben FE, Kiljunen T, Kangasmaki A. et al. Radiotherapy boost for the dominant intraprostatic cancer lesion-a systematic review and meta-analysis. Clinl Genitourin Cancer 2016; 14: 189-197
• 48 Rauscher I, Krönke M, König M. et al. Matched-pair comparison of (68)Ga-PSMA-11 PET/CT and (18)F-PSMA-1007 PET/CT: Frequency of pitfalls and detection efficacy in biochemical recurrence after radical prostatectomy. J Nucl Med 2020; 61: 51-57