Top

Published in:

Open Access 01-12-2023 | Prostate Cancer | Study protocol

DEPROMP Trial: the additive value of PSMA-PET/CT-guided biopsy for prostate cancer management in biopsy naïve men—study protocol for a randomized trial

Authors: P. Krausewitz, R. A. Bundschuh, F. C. Gaertner, M. Essler, U. Attenberger, J. Luetkens, G. Kristiansen, M. Muders, C-H. Ohlmann, S. Hauser, J. Ellinger, M. Ritter

Published in: Trials | Issue 1/2023

Abstract

Background

The primary objective is to determine the proportion of men with suspected prostate cancer (PCA) in whom the management plans are changed by additive gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) guided prostate biopsy (PET-TB) in combination with standard of care (SOC) using systematic (SB) and multiparametric magnetic resonance imaging-guided biopsy (MR-TB) compared with SOC alone. The major secondary objectives are to determine the additive value of the combined approach of SB + MR-TB + PET-TB (PET/MR-TB) for detecting clinically significant PCA (csPCA) compared to SOC; to determine sensitivity, specificity, positive and negative predictive value and diagnostic accuracy of imaging techniques, respective imaging classification systems, and each biopsy method; and to compare preoperatively defined tumor burden and biomarker expression and pathological tumor extent in prostate specimens.

Methods

The DEPROMP study is a prospective, open-label, interventional investigator-initiated trial. Risk stratification and management plans after PET/MR-TB are conducted randomized and blinded by different evaluation teams of experienced urologists based on histopathological analysis and imaging information: one including all results of the PET/MR-TB and one excluding the additional information gained by PSMA-PET/CT guided biopsy. The power calculation was centered on pilot data, and we will recruit up to 230 biopsy-naïve men who will undergo PET/MR-TB for suspected PCA. Conduct and reporting of MRI and PSMA-PET/CT will be performed in a blinded fashion.

Discussion

The DEPROMP Trial will be the first to evaluate the clinically relevant effects of the use of PSMA-PET/CT in patients with suspected PCA compared to current SOC. The study will provide prospective data to determine the diagnostic yields of additional PET-TB in men with suspected PCA and the impact on treatment plans in terms of intra- and intermodal changes. The results will allow a comparative analysis of risk stratification by each biopsy method, including a performance analysis of the corresponding rating systems. This will reveal potential intermethod and pre- and postoperative discordances of tumor stage and grading, providing the opportunity to critically assess the need for multiple biopsies.

Trial registration

German Clinical Study Register DRKS 00024134. Registered on 26 January 2021.

Available only for authorised users

Roth AJ, Weinberger MI, Nelson CJ. Prostate cancer: psychosocial implications and management. Future Oncol. 2008;4:561–8. https://doi.org/10.2217/14796694.4.4.561.CrossRefPubMed

Krausewitz P, Schmeller H, Luetkens J, Dabir D, Ellinger J, Ritter M, Conrad R. Prospective analysis of pain expectancy and experience during MR-fusion prostate biopsy: does reality match patients’ expectancy? World J Urol. 2022. https://doi.org/10.1007/s00345-022-04083-3.CrossRefPubMedPubMedCentral

Ahmed HU, El-ShaterBosaily A, Brown LC, Gabe R, Kaplan R, Parmar MK, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet. 2017;389:815–22. https://doi.org/10.1016/S0140-6736(16)32401-1.CrossRefPubMed

Mottet N, van den Bergh RCN, Briers E, van den Broeck T, Cumberbatch MG, de Santis M, 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. 2021;79:243–62. https://doi.org/10.1016/j.eururo.2020.09.042.CrossRefPubMed

Drost F-JH, Osses DF, Nieboer D, Steyerberg EW, Bangma CH, Roobol MJ, Schoots IG. Prostate MRI, with or without MRI-targeted biopsy, and systematic biopsy for detecting prostate cancer. Cochrane Database Syst Rev. 2019;4:CD012663. https://doi.org/10.1002/14651858.CD012663.pub2.CrossRefPubMed

Ahdoot M, Wilbur AR, Reese SE, Lebastchi AH, Mehralivand S, Gomella PT, et al. MRI-targeted, systematic, and combined biopsy for prostate cancer diagnosis. N Engl J Med. 2020;382:917–28. https://doi.org/10.1056/NEJMoa1910038.CrossRefPubMedPubMedCentral

Kasperzyk JL, Finn SP, Flavin R, Fiorentino M, Lis R, Hendrickson WK, et al. Prostate-specific membrane antigen protein expression in tumor tissue and risk of lethal prostate cancer. Cancer Epidemiol Biomarkers Prev. 2013;22:2354–63. https://doi.org/10.1158/1055-9965.EPI-13-0668.CrossRefPubMedPubMedCentral

Chang SS. Overview of prostate-specific membrane antigen. Rev Urol. 2004;6(Suppl 10):S13–8.PubMedPubMedCentral

Hofman MS, Lawrentschuk N, Francis RJ, Tang C, Vela I, Thomas P, 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;395:1208–16. https://doi.org/10.1016/S0140-6736(20)30314-7.CrossRefPubMed

10.

van Leeuwen PJ, Emmett L, Ho B, Delprado W, Ting F, Nguyen Q, Stricker PD. Prospective evaluation of 68Gallium-prostate-specific membrane antigen positron emission tomography/computed tomography for preoperative lymph node staging in prostate cancer. BJU Int. 2017;119:209–15. https://doi.org/10.1111/bju.13540.CrossRefPubMed

11.

Lopci E, Saita A, Lazzeri M, Lughezzani G, Colombo P, Buffi NM, et al. (68)Ga-PSMA positron emission tomography/computerized tomography for primary diagnosis of prostate cancer in men with contraindications to or negative multiparametric magnetic resonance imaging: a prospective observational study. J Urol. 2018;200:95–103. https://doi.org/10.1016/j.juro.2018.01.079.CrossRefPubMed

12.

Kesch C, Radtke J-P, Wintsche A, Wiesenfarth M, Luttje M, Gasch C, et al. Correlation between genomic index lesions and mpMRI and (68)Ga-PSMA-PET/CT imaging features in primary prostate cancer. Sci Rep. 2018;8:16708. https://doi.org/10.1038/s41598-018-35058-3.CrossRefPubMedPubMedCentral

13.

Kalapara AA, Nzenza T, Pan HYC, Ballok Z, Ramdave S, O’Sullivan R, et al. Detection and localisation of primary prostate cancer using (68) gallium prostate-specific membrane antigen positron emission tomography/computed tomography compared with multiparametric magnetic resonance imaging and radical prostatectomy specimen pathology. BJU Int. 2020;126:83–90. https://doi.org/10.1111/bju.14858.CrossRefPubMed

14.

Simopoulos DN, Natarajan S, Jones TA, Fendler WP, Sisk AE Jr, Marks LS. Targeted prostate biopsy using (68)gallium PSMA-PET/CT for image guidance. Urol Case Rep. 2017;14:11–4. https://doi.org/10.1016/j.eucr.2017.05.006.CrossRefPubMedPubMedCentral

15.

Zhang L-L, Li W-C, Xu Z, Jiang N, Zang S-M, Xu L-W, et al. (68)Ga-PSMA PET/CT targeted biopsy for the diagnosis of clinically significant prostate cancer compared with transrectal ultrasound guided biopsy: a prospective randomized single-centre study. Eur J Nucl Med Mol Imaging. 2021;48:483–92. https://doi.org/10.1007/s00259-020-04863-2.CrossRefPubMed

16.

Emmett L, Buteau J, Papa N, Moon D, Thompson J, Roberts MJ, et al. The additive diagnostic value of prostate-specific membrane antigen positron emission tomography computed tomography to multiparametric magnetic resonance imaging triage in the diagnosis of prostate cancer (PRIMARY): a prospective multicentre study. Eur Urol. 2021;80:682–9. https://doi.org/10.1016/j.eururo.2021.08.002.CrossRefPubMed

17.

Sonni I, Felker E, Lenis AT, Sisk AE, Bahri S, Auerbach MS, et al. Head-to-head comparison of 68Ga-PSMA-11 PET/CT and mpMRI in the detection, intra-prostatic localization, and local extension of primary prostate cancer: a single-center imaging study with histopathology gold-standard. J Clin Oncol. 2021;39:193. https://doi.org/10.1200/JCO.2021.39.6_suppl.193.CrossRef

18.

Tarr GP, Kashyap P, Dixit DD, Willams AK, Koya MP, Lim R. Utility of Ga(68) prostate-specific membrane antigen positron-emission tomography for pre-operative staging of high-risk prostate cancer in a prospective cohort. J Med Imaging Radiat Oncol. 2020;64:78–86. https://doi.org/10.1111/1754-9485.12988.CrossRefPubMed

19.

Artigas C, Diamand R, Shagera QA, Plouznikoff N, Fokoue F, Otte F-X, et al. Oligometastatic disease detection with (68)Ga-PSMA-11 PET/CT in hormone-sensitive prostate cancer patients (HSPC) with biochemical recurrence after radical prostatectomy: predictive factors and clinical impact. Cancers (Basel). 2021. https://doi.org/10.3390/cancers13194982.CrossRefPubMed

20.

Phillips R, Shi WY, Deek M, Radwan N, Lim SJ, Antonarakis ES, et al. Outcomes of observation vs stereotactic ablative radiation for oligometastatic prostate cancer: the ORIOLE phase 2 randomized clinical trial. JAMA Oncol. 2020;6:650–9. https://doi.org/10.1001/jamaoncol.2020.0147.CrossRefPubMedPubMedCentral

21.

Turkbey B, Rosenkrantz AB, Haider MA, Padhani AR, Villeirs G, Macura KJ, 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;76:340–51. https://doi.org/10.1016/j.eururo.2019.02.033.CrossRefPubMed

22.

Eiber M, Herrmann K, Calais J, Hadaschik B, Giesel FL, Hartenbach M, et al. Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE): proposed miTNM classification for the interpretation of PSMA-ligand PET/CT. J Nucl Med. 2018;59:469–78. https://doi.org/10.2967/jnumed.117.198119.CrossRefPubMed

23.

Roach PJ, Francis R, Emmett L, Hsiao E, Kneebone A, Hruby G, et al. The impact of (68)Ga-PSMA PET/CT on management intent in prostate cancer: results of an Australian prospective multicenter study. J Nucl Med. 2018;59:82–8. https://doi.org/10.2967/jnumed.117.197160.CrossRefPubMed

24.

Chen M, Zhang Q, Zhang C, Zhao X, Marra G, Gao J, et al. Combination of (68)Ga-PSMA PET/CT and multiparametric MRI improves the detection of clinically significant prostate cancer: a lesion-by-lesion analysis. J Nucl Med. 2019;60:944–9. https://doi.org/10.2967/jnumed.118.221010.CrossRefPubMedPubMedCentral

25.

Scheltema MJ, Chang JI, Stricker PD, van Leeuwen PJ, Nguyen QA, Ho B, et al. Diagnostic accuracy of (68) Ga-prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) and multiparametric (mp)MRI to detect intermediate-grade intra-prostatic prostate cancer using whole-mount pathology: impact of the addition of (68) Ga-PSMA PET to mpMRI. BJU Int. 2019;124(Suppl 1):42–9. https://doi.org/10.1111/bju.14794.CrossRefPubMed

26.

Zisman A, Leibovici D, Kleinmann J, Siegel YI, Lindner A. The impact of prostate biopsy on patient well-being: a prospective study of pain, anxiety and erectile dysfunction. J Urol. 2001;165:445–54. https://doi.org/10.1097/00005392-200102000-00023.CrossRefPubMed

Title: DEPROMP Trial: the additive value of PSMA-PET/CT-guided biopsy for prostate cancer management in biopsy naïve men—study protocol for a randomized trial
Authors: P. Krausewitz
R. A. Bundschuh
F. C. Gaertner
M. Essler
U. Attenberger
J. Luetkens
G. Kristiansen
M. Muders
C-H. Ohlmann
S. Hauser
J. Ellinger
M. Ritter
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Prostate Cancer
Magnetic Resonance Imaging
Magnetic Resonance Imaging
Prostate Cancer
Published in: Trials / Issue 1/2023
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-023-07197-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

DEPROMP Trial: the additive value of PSMA-PET/CT-guided biopsy for prostate cancer management in biopsy naïve men—study protocol for a randomized trial

Abstract

Background

Methods

Discussion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Discussion

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2023

Managing non-acute subdural hematoma using liquid materials: a Chinese randomized trial of middle meningeal artery treatment (MAGIC-MT)—protocol

Mobile phone text messaging plus motivational interviewing versus usual care: study protocol for a randomized controlled trial to evaluate effects on breastfeeding, child health, and survival outcomes, among women living with HIV (MTI-MI)

Individualized flow-controlled versus conventional pressure-controlled ventilation in on-pump heart surgery (FLOWVENTIN HEARTSURG): study protocol for a randomized controlled trial

A novel shared decision-making (SDM) tool for anticoagulation management in atrial fibrillation: protocol for a prospective, cluster randomized controlled trial

Child Adult Relationship Enhancement in Primary Care (PriCARE): study design/protocol for a randomized trial of a primary care-based group parenting intervention to prevent child maltreatment

Efficacy and safety of human umbilical cord-derived mesenchymal stem cells (hUC-MSC PLEB001) for the treatment of grade II–IV steroid-refractory acute graft-versus-host disease: a study protocol for a multicenter, randomized, double-blind, placebo-controlled, phase II trial