European Radiology

, Volume 29, Issue 1, pp 299–308 | Cite as

Twelve-month prostate volume reduction after MRI-guided transurethral ultrasound ablation of the prostate

  • David BonekampEmail author
  • M. B. Wolf
  • M. C. Roethke
  • S. Pahernik
  • B. A. Hadaschik
  • G. Hatiboglu
  • T. H. Kuru
  • I. V. Popeneciu
  • J. L. Chin
  • M. Billia
  • J. Relle
  • J. Hafron
  • K. R. Nandalur
  • R. M. Staruch
  • M. Burtnyk
  • M. Hohenfellner
  • H.-P. Schlemmer



To quantitatively assess 12-month prostate volume (PV) reduction based on T2-weighted MRI and immediate post-treatment contrast-enhanced MRI non-perfused volume (NPV), and to compare measurements with predictions of acute and delayed ablation volumes based on MR-thermometry (MR-t), in a central radiology review of the Phase I clinical trial of MRI-guided transurethral ultrasound ablation (TULSA) in patients with localized prostate cancer.

Materials and methods

Treatment day MRI and 12-month follow-up MRI and biopsy were available for central radiology review in 29 of 30 patients from the published institutional review board-approved, prospective, multi-centre, single-arm Phase I clinical trial of TULSA. Viable PV at 12 months was measured as the remaining PV on T2-weighted MRI, less 12-month NPV, scaled by the fraction of fibrosis in 12-month biopsy cores. Reduction of viable PV was compared to predictions based on the fraction of the prostate covered by the MR-t derived acute thermal ablation volume (ATAV, 55°C isotherm), delayed thermal ablation volume (DTAV, 240 cumulative equivalent minutes at 43°C thermal dose isocontour) and treatment-day NPV. We also report linear and volumetric comparisons between metrics.


After TULSA, the median 12-month reduction in viable PV was 88%. DTAV predicted a reduction of 90%. Treatment day NPV predicted only 53% volume reduction, and underestimated ATAV and DTAV by 36% and 51%.


Quantitative volumetry of the TULSA phase I MR and biopsy data identifies DTAV (240 CEM43 thermal dose boundary) as a useful predictor of viable prostate tissue reduction at 12 months. Immediate post-treatment NPV underestimates tissue ablation.

Key Points

• MRI-guided transurethral ultrasound ablation (TULSA) achieved an 88% reduction of viable prostate tissue volume at 12 months, in excellent agreement with expectation from thermal dose calculations.

• Non-perfused volume on immediate post-treatment contrast-enhanced MRI represents only 64% of the acute thermal ablation volume (ATAV), and reports only 60% (53% instead of 88% achieved) of the reduction in viable prostate tissue volume at 12 months.

• MR-thermometry-based predictions of 12-month prostate volume reduction based on 240 cumulative equivalent minute thermal dose volume are in excellent agreement with reduction in viable prostate tissue volume measured on pre- and 12-month post-treatment T2w-MRI.


High-intensity focused ultrasound ablation Prostate cancer Interventional magnetic resonance imaging Thermometry Biopsy, needle 



Active surveillance


Acute thermal ablation volume


Dice similarity coefficient


Delayed thermal ablation volume




Magnetic resonance imaging


Non-perfused volume


Prostate cancer


Prostate-specific antigen


Prostate volume


Radical prostatectomy


Transurethral ultrasound ablation


Ultrasound applicator



This study has received funding by Profound Medical Inc.

Compliance with ethical standards


The scientific guarantor of this publication is Heinz-Peter Schlemmer.

Conflict of interest

David Bonekamp is speaker for Profound Medical Inc.

Mathieu Burtnyk is director of clinical affairs of Profound Medical Inc. with a salary and stock options.

Robert Staruch is senior clinical scientist at Profound Medical Inc., with a salary and stock options.

Jason M. Hafron declares: Amgen-paid speaker, Armune Biosciences Inc, advisory board/paid speaker, Dendreon-Advisory Board, paid speaker, Myriad, and paid speaker, United Physicians- Board of directors

Heinz-Peter Schlemmer declares: Consulting fee or honorarium: Siemens, Curagita, Profound, Bayer. Travel support: Siemens, Curagita, Profound, Bayer. Board Member: Curagita. Consultancy: Curagita, Bayer. Grants/Grants pending: BMBF, Deutsche Krebshilfe, Dietmar-Hopp-Stiftung, Roland-Ernst-Stiftung. Payment for lectures: Siemens, Curagita, Profound, Bayer.

Boris Hadaschik declares: Personal fees: Janssen, BMS, Astrellas, Bayer. Grants: Janssen, Astrellas, BMS, German Cancer Aid, German Research Foundation.Grant: Profound Medical.

Gencay Hatiboglu declares: Consultancy for BMS.

Timur Kuru has nothing to declare.

James Relle has nothing to declare.

Maya Mueller-Wolf has nothing to declare.

Matthias Röthke declares consulting fee and payment for lectures: Siemens Healthineers, Curagita AG.

Sascha Pahernik reports personal fees from Bayer, personal fees from Astellas, personal fees from Janssen, outside the submitted work.

Valentin Popeneciu has nothing to declare.

Joseph Chin declares: Investigator and consultant for Profound Medical Inc., US HIFU, Endocare; Paid Advisory Board/Consultancy for Abbvie, Johnson & Johnson/Janssen, Amgen, Tersera, Novartis, Astellas, Bayer, Sanofi-Aventis.

Michele Billia has nothing to declare.

Kiran Nandalur has nothing to declare.

Markus Hohenfellner has nothing to declare.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional Review Board approval was obtained.

Study subjects or cohorts overlap

Some study subjects or cohorts have been previously reported in Chin JL, Billia M, Relle J, et al. Magnetic resonance imaging-guided transurethral ultrasound ablation of prostate tissue in patients with localized prostate cancer: a prospective Phase 1 clinical trial. Eur Urol. 2016;70(3):447–455.


• prospective

• experimental

• multicentre study


  1. 1.
    Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66(1):7–30CrossRefGoogle Scholar
  2. 2.
    Albertsen PC (2005) 20-Year Outcomes Following Conservative Management of Clinically Localized Prostate Cancer. JAMA 293(17):2095CrossRefGoogle Scholar
  3. 3.
    Resnick MJ, Koyama T, Fan K-H et al (2013) Long-Term Functional Outcomes after Treatment for Localized Prostate Cancer. N Engl J Med 368(5):436–445CrossRefGoogle Scholar
  4. 4.
    Tosoian JJ, Mamawala M, Epstein JI et al (2015) Intermediate and longer-term outcomes from a prospective active-surveillance program for favorable-risk prostate cancer. J Clin Oncol 33(30):3379–3385CrossRefGoogle Scholar
  5. 5.
    Klotz L, Vesprini D, Sethukavalan P et al (2015) Long-term follow-up of a large active surveillance cohort of patients with prostate cancer. J Clin Oncol 33(3):272–277CrossRefGoogle Scholar
  6. 6.
    Napoli A, Anzidei M, De Nunzio C et al (2013) Real-time magnetic resonance-guided high-intensity focused ultrasound focal therapy for localised prostate cancer: Preliminary experience. Eur Urol 63(2):395–398CrossRefGoogle Scholar
  7. 7.
    Mendez H, Passoni Maria N, Pow-Sang J, Jones Stephen J, Polascik J (2015) Comparison of Outcomes Between Preoperatively Potent Men Treated with Focal Versus Whole Gland Cryotherapy in a Matched Population. J Endourol 29(10):1193CrossRefGoogle Scholar
  8. 8.
    Azzouzi AR, Barret E, Moore CM et al (2013) TOOKAD® Soluble vascular-targeted photodynamic (VTP) therapy: Determination of optimal treatment conditions and assessment of effects in patients with localised prostate cancer. BJU Int 112(6):766–774CrossRefGoogle Scholar
  9. 9.
    Lepor H, Llukani E, Sperling D, Fütterer JJ (2015) Complications, Recovery, and Early Functional Outcomes and Oncologic Control Following In-bore Focal Laser Ablation of Prostate Cancer. Eur Urol 68(6):924–926CrossRefGoogle Scholar
  10. 10.
    Murray KS, Ehdaie B, Musser J et al (2016) Pilot Study to Assess Safety and Clinical Outcomes of Irreversible Electroporation for Partial Gland Ablation in Men with Prostate Cancer. J Urol. United States 196(3):883–890CrossRefGoogle Scholar
  11. 11.
    Cosset JM, Cathelineau X, Wakil G et al (2013) Focal brachytherapy for selected low-risk prostate cancers: A pilot study. Brachytherapy 12(4):331–337CrossRefGoogle Scholar
  12. 12.
    Zlotta AR, Djavan B, Matos C et al (1998) Percutaneous transperineal radiofrequency ablation of prostate tumour: safety, feasibility and pathological effects on human prostate cancer. Br J Urol 81(2):265–275Google Scholar
  13. 13.
    Chen JC, Moriarty JA, Derbyshire JA et al (2000) Prostate Cancer: MR Imaging and Thermometry during Microwave Thermal Ablation-Initial Experience. Radiology 214(1):290–297CrossRefGoogle Scholar
  14. 14.
    Valerio M, Cerantola Y, Eggener SE et al (2016) New and Established Technology in Focal Ablation of the Prostate: A Systematic Review. Eur Urol 71(1):17–34.
  15. 15.
    Feijoo ERC, Sivaraman A, Barret E et al (2016) Focal High-intensity Focused Ultrasound Targeted Hemiablation for Unilateral Prostate Cancer: A Prospective Evaluation of Oncologic and Functional Outcomes. Eur Urol 69(2):214–220.
  16. 16.
    Radtke JP, Wiesenfarth M, Kesch C et al (2017) Combined Clinical Parameters and Multiparametric Magnetic Resonance Imaging for Advanced Risk Modeling of Prostate Cancer-Patient-tailored Risk Stratification Can Reduce Unnecessary Biopsies. Eur Urol.
  17. 17.
    Radtke JP, Kuru TH, Bonekamp D et al (2016) Further reduction of disqualification rates by additional MRI-targeted biopsy with transperineal saturation biopsy compared with standard 12-core systematic biopsies for the selection of prostate cancer patients for active surveillance. Prostate Cancer Prostatic Dis 19(3):283–291CrossRefGoogle Scholar
  18. 18.
    Valerio M, Donaldson I, Emberton M et al (2015) Detection of clinically significant prostate cancer using magnetic resonance imaging-ultrasound fusion targeted biopsy: A systematic review. Eur Urol 68(1):8–19Google Scholar
  19. 19.
    Ahmed HU, El-Shater Bosaily A, Brown LC et al (2017) Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet 389(10071):815–822CrossRefGoogle Scholar
  20. 20.
    Siddiqui MM, Rais-Bahrami S, Turkbey B et al (2016) Comparison of MR/Ultrasound Fusion–Guided Biopsy With Ultrasound-Guided Biopsy for the Diagnosis of Prostate Cancer. JAMA 1210(4):390–397CrossRefGoogle Scholar
  21. 21.
    Ishihara Y, Calderon A, Watanabe H et al (1995) A precise and fast temperature mapping using water proton chemical shift. Magn Reson Med 34(6):814–823CrossRefGoogle Scholar
  22. 22.
    Ghai S, Louis AS, Van Vliet M et al (2015) Real-time MRI-guided focused ultrasound for focal therapy of locally confined low-risk prostate cancer: Feasibility and preliminary outcomes. Am J Roentgenol 205(2):W177–W184CrossRefGoogle Scholar
  23. 23.
    Eggener SE, Yousuf A, Watson S, Wang S, Oto A (2016) Phase II Evaluation of Magnetic Resonance Imaging Guided Focal Laser Ablation of Prostate Cancer. J Urol. United States 196(6):1670–1675CrossRefGoogle Scholar
  24. 24.
    Chopra R, Tang K, Burtnyk M et al (2009) Analysis of the spatial and temporal accuracy of heating in the prostate gland using transurethral ultrasound therapy and active MR temperature feedback. Phys Med Biol 54(9):2615–2633Google Scholar
  25. 25.
    Ramsay E, Mougenot C, Staruch R et al (2017) Evaluation of Focal Ablation of Magnetic Resonance Imaging Defined Prostate Cancer Using Magnetic Resonance Imaging Controlled Transurethral Ultrasound Therapy with Prostatectomy as the Reference Standard. J Urol 197(1):255–261Google Scholar
  26. 26.
    Chin JL, Billia M, Relle J et al (2016) Magnetic Resonance Imaging–Guided Transurethral Ultrasound Ablation of Prostate Tissue in Patients with Localized Prostate Cancer: A Prospective Phase 1 Clinical Trial. Eur Urol 70(3):447–455CrossRefGoogle Scholar
  27. 27.
    Chopra R, Colquhoun A, Burtnyk M et al (2012) MR imaging-controlled transurethral ultrasound therapy for conformal treatment of prostate tissue: initial feasibility in humans. Radiology 265(1):303–313Google Scholar
  28. 28.
    Sapareto SA, Dewey WC (1984) Thermal dose determination in cancer therapy. Int J Radiat Oncol Biol Phys 10(6):787–800CrossRefGoogle Scholar
  29. 29.
    McDannold NJ, King RL, Jolesz FA, Hynynen KH (2000) Usefulness of MR imaging-derived thermometry and dosimetry in determining the threshold for tissue damage induced by thermal surgery in rabbits. Radiology 216(11):517–523CrossRefGoogle Scholar
  30. 30.
    Burtnyk M, Hill T, Cadieux-Pitre H, Welch I (2015) Magnetic resonance image guided transurethral ultrasound prostate ablation: a preclinical safety and feasibility study with 28-day followup. J Urol 193(5):1669–1675Google Scholar
  31. 31.
    Burtnyk M, N’Djin WA, Kobelevskiy I, Bronskill M, Chopra R (2010) 3D conformal MRI-controlled transurethral ultrasound prostate therapy: validation of numerical simulations and demonstration in tissue-mimicking gel phantoms. Phys Med Biol. England 55(22):6817–6839CrossRefGoogle Scholar
  32. 32.
    Burtnyk M, Chopra R, Bronskill M (2010) Simulation study on the heating of the surrounding anatomy during transurethral ultrasound prostate therapy: a 3D theoretical analysis of patient safety. Med Phys 37(6):2862–2875Google Scholar
  33. 33.
    Boyes A, Tang K, Yaffe M, Sugar L, Chopra R, Bronskill M (2007) Prostate Tissue Analysis Immediately Following Magnetic Resonance Imaging Guided Transurethral Ultrasound Thermal Therapy. J Urol 178(3):1080–1085CrossRefGoogle Scholar
  34. 34.
    Ritter BF, Boskamp T, Homeyer A et al (2011) Medical Image Analysis: A Visual Approach. IEEE Pulse 2(6):60–70Google Scholar
  35. 35.
    Nolden M, Zelzer S, Seitel A et al (2013) The medical imaging interaction toolkit: Challenges and advances: 10 years of open-source development. Int J Comput Assist Radiol Surg 8(4):607–620CrossRefGoogle Scholar
  36. 36.
    Biermann K, Montironi R, Lopez-Beltran A, Zhang S, Cheng L (2010) Histopathological findings after treatment of prostate cancer using high-intensity focused ultrasound (HIFU). Prostate 70(11):1196–1200CrossRefGoogle Scholar
  37. 37.
    Ryan P, Finelli A, Lawrentschuk N et al (2012) Prostatic needle biopsies following primary high intensity focused ultrasound (HIFU) therapy for prostatic adenocarcinoma: histopathological features in tumour and non-tumour tissue. J Clin Pathol 65(8):729–734CrossRefGoogle Scholar
  38. 38.
    Dice LR (1945) Measures of the Amount of Ecologic Association Between Species. Ecology 26(3):297–302CrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2018

Authors and Affiliations

  • David Bonekamp
    • 1
    Email author
  • M. B. Wolf
    • 1
  • M. C. Roethke
    • 1
  • S. Pahernik
    • 2
  • B. A. Hadaschik
    • 2
  • G. Hatiboglu
    • 2
  • T. H. Kuru
    • 2
  • I. V. Popeneciu
    • 2
  • J. L. Chin
    • 3
  • M. Billia
    • 3
  • J. Relle
    • 4
  • J. Hafron
    • 4
  • K. R. Nandalur
    • 5
  • R. M. Staruch
    • 6
  • M. Burtnyk
    • 6
  • M. Hohenfellner
    • 2
  • H.-P. Schlemmer
    • 1
  1. 1.Department of Radiology (E010)German Cancer Research Center (DKFZ)HeidelbergGermany
  2. 2.Department of UrologyUniversity Hospital HeidelbergHeidelbergGermany
  3. 3.Department of UrologyUniversity of Western Ontario (UWO), London Health Sciences Center, Victoria HospitalLondonCanada
  4. 4.Department of UrologyBeaumont Health SystemRoyal OakUSA
  5. 5.Department of RadiologyBeaumont Health SystemRoyal OakUSA
  6. 6.Clinical ScienceProfound Medical Inc.TorontoCanada

Personalised recommendations