PURPOSE: To investigate if imaging biomarkers derived from 3-Tesla dual-tracer [(18)F]fluoromethylcholine (FMC) and [68Ga]Ga-PSMAHBED-CC conjugate 11 (PSMA)-positron emission tomography can adequately predict clinically significant prostate cancer (csPC). METHODS: We assessed 77 biopsy-proven PC patients who underwent 3T dual-tracer PET/mpMRI followed by radical prostatectomy (RP) between 2014 and 2017. We performed a retrospective lesion-based analysis of all cancer foci and compared it to whole-mount histopathology of the RP specimen. The primary aim was to investigate the pretherapeutic role of the imaging biomarkers FMC- and PSMA-maximum standardized uptake values (SUVmax) for the prediction of csPC and to compare it to the mpMRI-methods and PI-RADS score. RESULTS: Overall, we identified 104 cancer foci, 69 were clinically significant (66.3%) and 35 were clinically insignificant (33.7%). We found that the combined FMC+PSMA SUVmax were the only significant parameters (p < 0.001 and p = 0.049) for the prediction of csPC. ROC analysis showed an AUC for the prediction of csPC of 0.695 for PI-RADS scoring (95% CI 0.591 to 0.786), 0.792 for FMC SUVmax (95% CI 0.696 to 0.869), 0.852 for FMC+PSMA SUVmax (95% CI 0.764 to 0.917), and 0.852 for the multivariable CHAID model (95% CI 0.763 to 0.916). Comparing the AUCs, we found that FMC+PSMA SUVmax and the multivariable model were significantly more accurate for the prediction of csPC compared to PI-RADS scoring (p = 0.0123, p = 0.0253, respectively). CONCLUSIONS: Combined FMC+PSMA SUVmax seems to be a reliable parameter for the prediction of csPC and might overcome the limitations of PI-RADS scoring. Further prospective studies are necessary to confirm these promising preliminary results.

Comprehensive Cancer Center Medical University of Vienna 1090 Vienna Austria

Department of Biomedical Imaging and Image Guided Therapy Division of General and Pediatric Radiology Medical University of Vienna 1090 Vienna Austria

Department of Biomedical Imaging and Image Guided Therapy Division of Nuclear Medicine Medical University of Vienna 1090 Vienna Austria

Department of Urology 2nd Faculty of Medicine Charles University 116 36 Prague Czech Republic

Department of Urology and Andrology University Hospital Krems 3500 Krems Austria

Department of Urology Medical University of Vienna 1090 Vienna Austria

Department of Urology University of Texas Southwestern Dallas TX 75390 USA

Department of Urology Weill Medical College of Cornell University New York NY 10021 USA

HistoConsultingHartenbach 89081 Ulm Germany

Hourani Center for Applied Scientific Research Al Ahliyya Amman University Amman 19328 Jordan

Karl Landsteiner Institute of Urology and Andrology 1010 Vienna Austria

Karl Landsteiner University of Health Sciences 3500 Krems Austria

Working Group of Diagnostic Imaging in Urology Austrian Society of Urology 1090 Vienna Austria

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Ferlay J., Colombet M., Soerjomataram I., Dyba T., Randi G., Bettio M., Gavin A., Visser O., Bray F. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. Eur. J. Cancer. 2018;103:356–387. doi: 10.1016/j.ejca.2018.07.005. PubMed DOI

Matoso A., Epstein J.I. Defining clinically significant prostate cancer on the basis of pathological findings. Histopathology. 2019;74:135–145. doi: 10.1111/his.13712. PubMed DOI

Epstein J.I., Egevad L., Amin M.B., Delahunt B., Srigley J.R., Humphrey P.A. The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am. J. Surg. Pathol. 2016;40:244–252. doi: 10.1097/PAS.0000000000000530. PubMed DOI

Mottet N., van den Bergh R.C., Briers E., Van den Broeck T., Cumberbatch M.G., De Santis M., Fanti S., Fossati N., Gandaglia G., Gillessen S., et al. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer—2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur. Urol. 2020;79:243–262. doi: 10.1016/j.eururo.2020.09.042. PubMed DOI

Hayes J.H., Ollendorf D.A., Pearson S.D., Barry M.J., Kantoff P., Lee P.A., McMahon P.M. Observation Versus Initial Treatment for Men With Localized, Low-Risk Prostate Cancer: A Cost-Effectiveness Analysis. Ann. Intern. Med. 2013;158:853. doi: 10.7326/0003-4819-158-12-201306180-00002. PubMed DOI PMC

Lu-Yao G.L., Albertsen P.C., Moore D.F., Shih W., Lin Y., DiPaola R.S., Barry M.J., Zietman A., O’Leary M., Walker-Corkery E., et al. Outcomes of Localized Prostate Cancer Following Conservative Management. JAMA. 2009;302:1202–1209. doi: 10.1001/jama.2009.1348. PubMed DOI PMC

Ali A., Hoyle A., Baena E., Clarke N.W. Identification and evaluation of clinically significant prostate cancer. Curr. Opin. Urol. 2017;27:217–224. doi: 10.1097/MOU.0000000000000385. PubMed DOI

Johnson D.C., Raman S.S., Mirak S.A., Kwan L., Bajgiran A.M., Hsu W., Maehara C.K., Ahuja P., Faiena I., Pooli A., et al. Detection of Individual Prostate Cancer Foci via Multiparametric Magnetic Resonance Imaging. Eur. Urol. 2019;75:712–720. doi: 10.1016/j.eururo.2018.11.031. PubMed DOI

Drost F.H., Osses D.F., Nieboer D., Steyerberg E.W., Bangma C.H., Roobol M.J., Schoots I.G. Prostate MRI, with or without MRI-targeted biopsy, and systematic biopsy for detecting prostate cancer. Cochrane Database Syst. Rev. 2019;4:CD012663. doi: 10.1002/14651858.CD012663.pub2. PubMed DOI PMC

Turkbey B., Rosenkrantz A.B., Haider M.A., Padhani A.R., Villeirs G., Macura K.J., Tempany C.M., Choyke P.L., Cornud F., Margolis D.J., et al. Prostate Imaging Reporting and Data System Version 2.1: 2019 Update of Prostate Imaging Reporting and Data System Version 2. Eur. Urol. 2019;76:340–351. doi: 10.1016/j.eururo.2019.02.033. PubMed DOI

Barkovich E.J., Shankar P.R., Westphalen A.C. A Systematic Review of the Existing Prostate Imaging Reporting and Data System Version 2 (PI-RADSv2) Literature and Subset Meta-Analysis of PI-RADSv2 Categories Stratified by Gleason Scores. Am. J. Roentgenol. 2019;212:847–854. doi: 10.2214/AJR.18.20571. PubMed DOI

Mehralivand S., Shih J.H., Rais-Bahrami S., Oto A., Bednarova S., Nix J.W., Thomas J.V., Gordetsky J.B., Gaur S., Harmon S.A., et al. A Magnetic Resonance Imaging–Based Prediction Model for Prostate Biopsy Risk Stratification. JAMA Oncol. 2018;4:678. doi: 10.1001/jamaoncol.2017.5667. PubMed DOI PMC

Hartenbach M., Hartenbach S., Bechtloff W., Danz B., Kraft K., Klemenz B., Sparwasser C., Hacker M. Combined PET/MRI improves diagnostic accuracy in patients with prostate cancer: A prospective diagnostic trial. Clin. Cancer Res. 2014;20:3244–3253. doi: 10.1158/1078-0432.CCR-13-2653. PubMed DOI

Grubmüller B., Baltzer P., Hartenbach S., D’Andrea D., Helbich T.H., Haug A.R., Goldner G.M., Wadsak W., Pfaff S., Mitterhauser M., et al. PSMA Ligand PET/MRI for Primary Prostate Cancer: Staging Performance and Clinical Impact. Clin. Cancer Res. 2018;24:6300–6307. doi: 10.1158/1078-0432.CCR-18-0768. PubMed DOI

EEiber M., Weirich G., Holzapfel K., Souvatzoglou M., Haller B., Rauscher I., Beer A.J., Wester H.-J., Gschwend J., Schwaiger M., et al. Simultaneous 68Ga-PSMA HBED-CC PET/MRI Improves the Localization of Primary Prostate Cancer. Eur. Urol. 2016;70:829–836. doi: 10.1016/j.eururo.2015.12.053. PubMed DOI

Ahmed H.U., El-Shater Bosaily A., Brown L.C., Gabe R., Kaplan R., Parmar M.K., Collaco-Moraes Y., Ward K., Hindley R.G., Freeman A., et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): A paired validating confirmatory study. Lancet. 2017;389:815–822. doi: 10.1016/S0140-6736(16)32401-1. PubMed DOI

Polanec S.H., Helbich T.H., Bickel H., Wengert G.J., Pinker K., Spick C., Clauser P., Susani M., Shariat S., Baltzer P.A. Quantitative Apparent Diffusion Coefficient Derived From Diffusion-Weighted Imaging Has the Potential to Avoid Unnecessary MRI-Guided Biopsies of mpMRI-Detected PI-RADS 4 and 5 Lesions. Investig. Radiol. 2018;53:736–741. doi: 10.1097/RLI.0000000000000498. PubMed DOI

Chatterjee A., He D., Fan X., Antic T., Jiang Y., Eggener S., Karczmar G.S., Oto A. Diagnosis of Prostate Cancer by Use of MRI-Derived Quantitative Risk Maps: A Feasibility Study. Am. J. Roentgenol. 2019;213:W66–W75. doi: 10.2214/AJR.18.20702. PubMed DOI

Wang Y., Tadimalla S., Rai R., Goodwin J., Foster S., Liney G., Holloway L., Haworth A. Quantitative MRI: Defining repeatability, reproducibility and accuracy for prostate cancer imaging biomarker development. Magn. Reson. Imaging. 2021;77:169–179. doi: 10.1016/j.mri.2020.12.018. PubMed DOI

Berger I., Annabattula C., Lewis J., Shetty D.V., Kam J., MacLean F., Arianayagam M., Canagasingham B., Ferguson R., Khadra M., et al. 68Ga-PSMA PET/CT vs. mpMRI for locoregional prostate cancer staging: Correlation with final histopathology. Prostate Cancer Prostatic Dis. 2018;21:204–211. doi: 10.1038/s41391-018-0048-7. PubMed DOI

Metser U., Ortega C., Perlis N., Lechtman E., Berlin A., Anconina R., Eshet Y., Chan R., Veit-Haibach P., van der Kwast T.H., et al. Detection of clinically significant prostate cancer with 18F-DCFPyL PET/multiparametric MR. Eur. J. Nucl. Med. Mol. Imaging. 2021;48:3702–3711. doi: 10.1007/s00259-021-05355-7. PubMed DOI

Jairath N.K., Pra A.D., Vince R., Dess R.T., Jackson W.C., Tosoian J.J., McBride S.M., Zhao S.G., Berlin A., Mahal B.A., et al. A Systematic Review of the Evidence for the Decipher Genomic Classifier in Prostate Cancer. Eur. Urol. 2020;79:374–383. doi: 10.1016/j.eururo.2020.11.021. PubMed DOI

Sommariva S., Tarricone R., Lazzeri M., Ricciardi W., Montorsi F. Prognostic Value of the Cell Cycle Progression Score in Patients with Prostate Cancer: A Systematic Review and Meta-analysis. Eur. Urol. 2016;69:107–115. doi: 10.1016/j.eururo.2014.11.038. PubMed DOI

Hectors S., Cherny M., Yadav K.K., Beksaç A.T., Thulasidass H., Lewis S., Davicioni E., Wang P., Tewari A.K., Taouli B. Radiomics Features Measured with Multiparametric Magnetic Resonance Imaging Predict Prostate Cancer Aggressiveness. J. Urol. 2019;202:498–505. doi: 10.1097/JU.0000000000000272. PubMed DOI

Jambor I., Falagario U., Ratnani P., Msc I.M.P., Demir K., Merisaari H., Sobotka S., Haines G.K., Martini A., Beksac A.T., et al. Prediction of biochemical recurrence in prostate cancer patients who underwent prostatectomy using routine clinical prostate multiparametric MRI and decipher genomic score. J. Magn. Reson. Imaging. 2020;51:1075–1085. doi: 10.1002/jmri.26928. PubMed DOI

Hofman M.S., Emmett L., Sandhu S., Iravani A., Joshua A.M., Goh J.C., Pattison D.A., Tan T.H., Kirkwood I.D., Ng 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. doi: 10.1016/S0140-6736(21)00237-3. PubMed DOI

Thang S.P., Violet J., Sandhu S., Iravani A., Akhurst T., Kong G., Kumar A.R., Murphy D.G., Williams S.G., Hicks R.J., et al. Poor Outcomes for Patients with Metastatic Castration-resistant Prostate Cancer with Low Prostate-specific Membrane Antigen (PSMA) Expression Deemed Ineligible for 177Lu-labelled PSMA Radioligand Therapy. Eur. Urol. Oncol. 2019;2:670–676. doi: 10.1016/j.euo.2018.11.007. PubMed DOI

Assessment of PSMA Expression of Healthy Organs in Different Stages of Prostate Cancer Using [68Ga]Ga-PSMA-11-PET Examinations