Abstract
Background
Prostate cancer focal therapy aims to minimize the side-effects of whole gland treatments, such as radical prostatectomy and radiotherapy without compromising oncological efficacy. However, concerns exist regarding the multifocal nature of prostate cancer and the lack of long-term oncological data for this form of treatment. In recent years, the routine adoption of multi-parametric magnetic resonance imaging (mpMRI) of the prostate has improved our ability to select candidates for focal therapy and to accurately deliver this form of prostate cancer treatment.
Methods
We performed a review of the literature to provide a summary of the oncological and functional outcomes of men receiving primary prostate focal therapy. Furthermore, we discuss the impact of the routine implementation of mpMRI as part of the initial prostate cancer diagnostic pathway on the selection of candidates and delivery of focal therapy. Finally, we summarize knowledge gaps in the field and highlight active clinical trials in this arena.
Results
Primary focal therapy involves the application of one of a number of energies that ablate tissue, such as cryotherapy and high intensity focused ultrasound (HIFU). Success is principally dependent on highly accurate patient selection and disease localization underpinned in large part by the routine integration of pre-biopsy mpMRI. Prospective medium-term follow-up data for primary HIFU and cryotherapy for men with intermediate-risk disease have shown acceptable cancer control with low risk of side effects and complications. Additional research is needed to clearly define an appropriate follow-up approach and to guide the management of in- and out-of-field recurrences. Multiple comparative trials with randomization against standard care are currently underway in men with intermediate- and high-risk prostate cancer.
Conclusion
The widespread adoption of prostate mpMRI has led to improved disease localization, enabling the performance of focal therapy as a viable treatment strategy for men with low volume intermediate-risk prostate cancer.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 4 print issues and online access
$259.00 per year
only $64.75 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Caverly TJ, Hayward RA, Reamer E, Zikmund-Fisher BJ, Connochie D, Heisler M, et al. Presentation of benefits and harms in US cancer screening and prevention guidelines: systematic review. J Natl Cancer Inst. 2016;108:djv436.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. Cancer J Clin. 2019;69:7–34.
Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, et al. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med. 2016;375:1415–24.
Moyer VA. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2012;157:120–34.
NICE. Guideline Updates Team UK. Prostate cancer: diagnosis and management. 2019.
Mottet N, Bellmunt J, Briers E, Bolla M, Bourke L, Cornford P, et al. Members of the EAU-ESTRO-ESUR-SIOG Prostate Cancer Guidelines Panel.: EAU-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer. Edn. presented at the EAU; 2019.
Grossman DC, Curry SJ, Owens DK, Bibbins-Domingo K, Caughey AB, Davidson KW, et al. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018;319:1901–13.
Bass EJ, Ahmed HU. Focal therapy in prostate cancer: a review of seven common controversies. Cancer Treat Rev. 2016;51:27–34.
Shah TT, Kasivisvanathan V, Jameson C, Freeman A, Emberton M, Ahmed HU. Histological outcomes after focal high-intensity focused ultrasound and cryotherapy. World J Urol. 2015;33:955–64.
Kovács G, Cosset J, Carey B. Focal radiotherapy as focal therapy of prostate cancer. Curr Opin Urol. 2014;24:231–5.
Nguyen PL, Chen M, Zhang Y, Tempany CM, Cormack RA, Beard CJ, et al. Updated results of magnetic resonance imaging guided partial prostate brachytherapy for favorable risk prostate cancer: implications for focal therapy. J Urol. 2012;188:1151–6.
Kishan AU, Dang A, Katz AJ, Mantz CA, Collins SP, Aghdam N, et al. Long-term outcomes of stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer. JAMA Netw Open. 2019;2:e188006.
Ahmed HU, Bosaily AE, 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.
Kasivisvanathan V, Rannikko AS, Borghi M, Panebianco V, Mynderse LA, Vaarala MH, et al. MRI-targeted or standard biopsy for prostate-cancer diagnosis. N Engl J Med. 2018;378:1767–77.
Siddiqui MM, Rais-Bahrami S, Turkbey B, George AK, Rothwax J, Shakir N, et al. Comparison of MR/ultrasound fusion–guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer. JAMA. 2015;313:390–7.
Haffner J, Lemaitre L, Puech P, Haber G, Leroy X, Jones JS, et al. Role of magnetic resonance imaging before initial biopsy: comparison of magnetic resonance imaging‐targeted and systematic biopsy for significant prostate cancer detection. BJU Int. 2011;108(8b):E171–8.
Moldovan PC, Van den Broeck T, Sylvester R, Marconi L, Bellmunt J, van den Bergh, et al. What is the negative predictive value of multiparametric magnetic resonance imaging in excluding prostate cancer at biopsy? A systematic review and meta-analysis from the European Association of Urology Prostate Cancer Guidelines Panel. Eur Urol. 2017;72:250–66.
Rouvière O, Puech P, Renard-Penna R, Claudon M, Roy C, Mège-Lechevallier F, et al. Use of prostate systematic and targeted biopsy on the basis of multiparametric MRI in biopsy-naive patients (MRI-FIRST): a prospective, multicentre, paired diagnostic study. Lancet Oncol. 2019;20:100–9.
Miah S, Hosking-Jervis F, Connor MJ, Eldred-Evans D, Shah TT, Arya M, et al. A multi-centre analysis of detection of clinically significant prostate cancer following transperineal image-fusion targeted and non-targeted systematic prostate biopsy in men at risk. Eur Urol Oncol. 2019. [Online ahead of print].
Mannaerts CK, Kajtazovic A, Lodeizen OA, Gayet M, Engelbrecht MR, Jager GJ, et al. The added value of systematic biopsy in men with suspicion of prostate cancer undergoing multiparametric MRI-targeted biopsy. Urol Oncol. 2019.
Mottet N, Bellmunt J, Briers E, Bolla M, Bourke L, Cornford P, et al. Members of the EAU–ESTRO–ESUR–SIOG Prostate Cancer Guidelines Panel. EAU–ESTRO–ESUR–SIOG Guidelines on Prostate Cancer. Prostate Cancer; https://uroweb.org/guideline/prostate-cancer/. Accessed 14 Apr 2019.
NHS England. Implementing a timed prostate cancer diagnostic pathway. 2018.
Ahmed HU. The index lesion and the origin of prostate cancer. N Engl J Med. 2009;361:1704–6.
Tay KJ, Scheltema MJ, Ahmed HU, Barret E, Coleman JA, Dominguez-Escrig J, et al. Patient selection for prostate focal therapy in the era of active surveillance: an International Delphi Consensus Project. Prostate Cancer Prostatic Dis. 2017;20:294.
Bott SR, Ahmed HU, Hindley RG, Abdul-Rahman A, Freeman A, Emberton M. The index lesion and focal therapy: an analysis of the pathological characteristics of prostate cancer. BJU Int. 2010;106:1607–11.
Shah TT, Peters M, Eldred-Evans D, Miah S, Yap T, Faure-Walker NA, et al. Early-medium-term outcomes of primary focal cryotherapy to treat nonmetastatic clinically significant prostate cancer from a prospective multicentre registry. Eur Urol. 2019;76:98–105.
Vaidya JS, Joseph DJ, Tobias JS, Bulsara M, Wenz F, Saunders C, et al. Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial. Lancet. 2010;376:91–102.
Kunath F, Schmidt S, Krabbe L, Miernik A, Dahm P, Cleves A, et al. Partial nephrectomy versus radical nephrectomy for clinical localised renal masses. Cochrane Datab Syst Rev. 2017;5:CD012045.
Lawrentschuk N, Zuniga A, Grabowksi AC, Rendon RA, Jewett MA. Partial orchiectomy for presumed malignancy in patients with a solitary testis due to a prior germ cell tumor: a large North American experience. J Urol. 2011;185:508–13.
Bissada NK, Yakout HH, Fahmy WE, GAYED MS, Touijer AK, Greene GF, et al. Multi-institutional long-term experience with conservative surgery for invasive penile carcinoma. J Urol. 2003;169:500–2.
Villers A, McNeal JE, Freiha FS, Stamey TA. Multiple cancers in the prostate. Morphologic features of clinically recognized versus incidental tumors. Cancer. 1992;70:2313–8.
Wise AM, Stamey TA, McNeal JE, Clayton JL. Morphologic and clinical significance of multifocal prostate cancers in radical prostatectomy specimens. Urology. 2002;60:264–9.
Ohori M, Eastham JA, Koh H, Kuroiwa K, Slawin KM, Wheeler TM, et al. Is focal therapy reasonable in patients with early stage prostate cancer (CAP)-an analysis of radical prostatectomy (RP) specimens. J Urol. 2006;175:507.
Liu W, Laitinen S, Khan S, Vihinen M, Kowalski J, Yu G, et al. Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer. Nat Med. 2009;15:559.
Attard G, Clark J, Ambroisine L, Fisher G, Kovacs G, Flohr P, et al. Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer. Oncogene. 2008;27:253.
Guo CC, Wang Y, Xiao L, Troncoso P, Czerniak BA. The relationship of TMPRSS2-ERG gene fusion between primary and metastatic prostate cancers. Hum Pathol. 2012;43:644–9.
Haffner MC, Mosbruger T, Esopi DM, Fedor H, Heaphy CM, Walker DA, et al. Tracking the clonal origin of lethal prostate cancer. J Clin Investig. 2013;123:4918–22.
Bill-Axelson A, Holmberg L, Garmo H, Taari K, Busch C, Nordling S, et al. Radical prostatectomy or watchful waiting in prostate cancer—29-year follow-up. N Engl J Med. 2018;379:2319–29.
Wilt TJ, Jones KM, Barry MJ, Andriole GL, Culkin D, Wheeler T, et al. Follow-up of prostatectomy versus observation for early prostate cancer. N Engl J Med. 2017;377:132–42.
van der Poel HenkG, van den Bergh, Roderick CN, Briers E, Cornford P, Govorov A, et al. Focal therapy in primary localised prostate cancer: the European Association of Urology position in 2018. Eur Urol. 2018;74:84–91.
Donaldson IA, Alonzi R, Barratt D, Barret E, Berge V, Bott S, et al. Focal therapy: patients, interventions, and outcomes—a report from a consensus meeting. Eur Urol. 2015;67:771–7.
Valerio M, Ahmed HU, Emberton M, Lawrentschuk N, Lazzeri M, Montironi R, et al. The role of focal therapy in the management of localised prostate cancer: a systematic review. Eur Urol 2014;66:732–51.
Miah S, Eldred-Evans D, Simmons LA, Shah TT, Kanthabalan A, Arya M, et al. Patient reported outcome measures for transperineal template prostate mapping biopsies in the PICTURE study. J Urol. 2018;200:1235–40.
Kum F, Jones A, Nigam R. Factors influencing urinary retention after transperineal template biopsy of the prostate: outcomes from a regional cancer centre. World J Urol. 2019;37:337–42.
Connor MJ, Miah S, Jayadevan R, Khoo C, Eldred-Evans D, Shah TT, et al. Value of systematic sampling in an mp-MRI targeted prostate biopsy strategy. Transl Androl Urol. 2019. [Online ahead of print].
Shah TT, Ahmed H, Kanthabalan A, Lau B, Ghei M, Maraj B, et al. Focal cryotherapy of localized prostate cancer: a systematic review of the literature. Exp Rev Anticancer Ther. 2014;14:1337–47.
Hectors SJ, Jacobs I, Moonen CT, Strijkers GJ, Nicolay K. MRI methods for the evaluation of high intensity focused ultrasound tumor treatment: current status and future needs. Magn Reson Med. 2016;75:302–17.
Ting F, Tran M, Böhm M, Siriwardana A, Van Leeuwen PJ, Haynes AM, et al. Focal irreversible electroporation for prostate cancer: functional outcomes and short-term oncological control. Prostate Cancer Prostatic Dis. 2016;19:46.
Eymerit-Morin C, Zidane M, Lebdai S, Triau S, Azzouzi AR, Rousselet M. Histopathology of prostate tissue after vascular-targeted photodynamic therapy for localized prostate cancer. Virchows Arch. 2013;463:547–52.
Oto A, Sethi I, Karczmar G, McNichols R, Ivancevic MK, Stadler WM, et al. MR imaging–guided focal laser ablation for prostate cancer: phase I trial. Radiology. 2013;267:932–40.
Azzouzi A, Barret E, Moore CM, Villers A, Allen C, Scherz A, et al. TOOKAD® soluble vascular‐targeted photodynamic (VTP) therapy: determination of optimal treatment conditions and assessment of effects in patients with localised prostate cancer. BJU Int. 2013;112:766–74.
Le Nobin J, Rosenkrantz AB, Villers A, Orczyk C, Deng F, Melamed J, et al. Image guided focal therapy for magnetic resonance imaging visible prostate cancer: defining a 3-dimensional treatment margin based on magnetic resonance imaging histology co-registration analysis. J Urol. 2015;194:364–70.
Priester A, Natarajan S, Khoshnoodi P, Margolis DJ, Raman SS, Reiter RE, et al. Magnetic resonance imaging underestimation of prostate cancer geometry: use of patient specific molds to correlate images with whole mount pathology. J Urol. 2017;197:320–6.
Muller BG, Van den Bos W, Brausi M, Fütterer JJ, Ghai S, Pinto PA, et al. Follow-up modalities in focal therapy for prostate cancer: results from a Delphi consensus project. World J Urol. 2015;33:1503–9.
Punwani S, Emberton M, Walkden M, Sohaib A, Freeman A, Ahmed H, et al. Prostatic cancer surveillance following whole-gland high-intensity focused ultrasound: comparison of MRI and prostate-specific antigen for detection of residual or recurrent disease. Br J Radiol. 2012;85:720–8.
Dickinson L, Ahmed HU, Hindley RG, McCartan N, Freeman A, Allen C, et al. Prostate-specific antigen vs. magnetic resonance imaging parameters for assessing oncological outcomes after high intensity–focused ultrasound focal therapy for localized prostate cancer. Urol Oncol. 2017;35:30.e9–15.
Muller BG, Fütterer JJ, Gupta RT, Katz A, Kirkham A, Kurhanewicz J, et al. The role of magnetic resonance imaging (MRI) in focal therapy for prostate cancer: recommendations from a consensus panel. BJU Int. 2014;113:218–27.
Dickinson L, Ahmed HU, Kirkham AP, Allen C, Freeman A, Barber J, et al. A multi-centre prospective development study evaluating focal therapy using high intensity focused ultrasound for localised prostate cancer: the INDEX study. Contemp Clin Trials. 2013;36:68–80.
Dickinson L, Arya M, Afzal N, Cathcart P, Charman SC, Cornaby A, et al. Medium-term outcomes after whole-gland high-intensity focused ultrasound for the treatment of nonmetastatic prostate cancer from a multicentre registry cohort. Eur Urol. 2016;70:668–74.
Guillaumier S, Peters M, Arya M, Afzal N, Charman S, Dudderidge T, et al. A multicentre study of 5-year outcomes following focal therapy in treating clinically significant nonmetastatic prostate cancer. Eur Urol. 2018;74:422–9.
Bahn D, de Castro A, Andre L, Gill IS, Hung AJ, Silverman P, et al. Focal cryotherapy for clinically unilateral, low-intermediate risk prostate cancer in 73 men with a median follow-up of 3.7 years. Eur Urol. 2012;62:55–63.
Ward JF, Jones JS. Focal cryotherapy for localized prostate cancer: a report from the national Cryo On‐Line Database (COLD) Registry. BJU Int. 2012;109:1648–54.
Ellis DS, Manny TB Jr, Rewcastle JC. Focal cryosurgery followed by penile rehabilitation as primary treatment for localized prostate cancer: initial results. Urology. 2007;70:S9–15.
Van Velthoven R, Aoun F, Marcelis Q, Albisinni S, Zanaty M, Lemort M, et al. A prospective clinical trial of HIFU hemiablation for clinically localized prostate cancer. Prostate Cancer Prostatic Dis. 2016;19:79.
Ahmed HU, Freeman A, Kirkham A, Sahu M, Scott R, Allen C, et al. Focal therapy for localized prostate cancer: a phase I/II trial. J Urol. 2011;185:1246–55.
Stabile A, Orczyk C, Hosking‐Jervis F, Giganti F, Arya M, Hindley RG, et al. Medium‐term oncological outcomes in a large cohort of men treated with either focal or hemi‐ablation using high‐intensity focused ultrasonography for primary localized prostate cancer. BJU Int. 2019;124:431–40.
Ahmed HU, Hindley RG, Dickinson L, Freeman A, Kirkham AP, Sahu M, et al. Focal therapy for localised unifocal and multifocal prostate cancer: a prospective development study. Lancet Oncol. 2012;13:622–32.
Valerio M, Dickinson L, Ali A, Ramachadran N, Donaldson I, Mccartan N, et al. Nanoknife electroporation ablation trial: a prospective development study investigating focal irreversible electroporation for localized prostate cancer. J Urol. 2017;197:647–54.
Lepor H, Llukani E, Sperling D, Fütterer JJ. Complications, recovery, and early functional outcomes and oncologic control following in-bore focal laser ablation of prostate cancer. Eur Urol. 2015;68:924–6.
Azzouzi A, Vincendeau S, Barret E, Cicco A, Kleinclauss F, van der Poel, et al. Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial. Lancet Oncol. 2017;18:181–91.
Merriel SW, Hetherington L, Seggie A, Castle JT, Cross W, Roobol MJ, et al. Best practice in active surveillance for men with prostate cancer: A prostate cancer UK consensus statement. BJU Int. 2019;24:47–54.
Oishi M, Gill IS, Ashrafi AN, Lin-Brande M, Nassiri N, Shin T, et al. Primary whole-gland cryoablation for prostate cancer: biochemical failure and clinical recurrence at 5.6 years of follow-up. Eur Urol. 2019;75:208–14.
Marconi L, Stonier T, Tourinho-Barbosa R, Moore C, Ahmed HU, Cathelineau X, et al. Robot-assisted radical prostatectomy after focal therapy: oncological, functional outcomes and predictors of recurrence. Eur Urol. 2019;76:27–30.
Hopper AB, Sandhu AP, Parsons JK, Rose B, Einck JP. Salvage image guided radiation therapy to the prostate after cryotherapy failure. Adv Radiat Oncol. 2018;3:52–6.
Ganzer R, Robertson CN, Ward JF, Brown SC, Conti GN, Murat FJ, et al. Correlation of prostate‐specific antigen nadir and biochemical failure after high‐intensity focused ultrasound of localized prostate cancer based on the Stuttgart failure criteria–analysis from the@‐Registry. BJU Int. 2011;108:E196–201.
Roy HK, Brendler CB, Subramanian H, Zhang D, Maneval C, Chandler J, et al. Nanocytological field carcinogenesis detection to mitigate overdiagnosis of prostate cancer: a proof of concept study. PLoS ONE. 2015;10:e0115999.
Bahn D, de Castro A, Andre L, Gill IS, Hung AJ, Silverman P, et al. Focal cryotherapy for clinically unilateral, low-intermediate risk prostate cancer in 73 men with a median follow-up of 3.7 years. Eur Urol. 2012;62:55–63.
Author information
Authors and Affiliations
Contributions
MJC, RN, HUA, and MAG conceived the idea of the article. MJC and MAG wrote the first version and all authors contributed significant editing to the final version.
Corresponding author
Ethics declarations
Conflict of interest
MJC is funded by the Wellcome Trust and University College London Hospital (UCLH) Charity. MAG: None. HUA's research is supported by core funding from the United Kingdom’s National Institute of Health Research (NIHR) Imperial Biomedical Research Centre. HUA currently receives funding from the Wellcome Trust, Medical Research Council (UK), Prostate Cancer UK, Cancer Research UK, The BMA Foundation, The Urology Foundation, The Imperial Health Charity, University College London Hospital (UCLH) Charity Sonacare Inc., Trod Medical and Sophiris Biocorp for trials and studies in prostate cancer. HUA is a paid medical consultant for Sophiris Biocorp, Sonacare Inc. and BTG/Galil. HUA is a paid proctor for HIFU, cryotherapy and Rezum water vapor therapy. RN: None.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Connor, M.J., Gorin, M.A., Ahmed, H.U. et al. Focal therapy for localized prostate cancer in the era of routine multi-parametric MRI. Prostate Cancer Prostatic Dis 23, 232–243 (2020). https://doi.org/10.1038/s41391-020-0206-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41391-020-0206-6
This article is cited by
-
Landmarks in the evolution of prostate biopsy
Nature Reviews Urology (2023)
-
Clinical efficacy of prostate PI-RADS V2.1 score combined with serum PSA-related indicators in the detection of gray zone prostate cancer
International Urology and Nephrology (2023)
-
Real-Time and Delayed Imaging of Tissue and Effects of Prostate Tissue Ablation
Current Urology Reports (2023)
-
Oncological and functional outcome after partial prostate HIFU ablation with Focal-One®: a prospective single-center study
Prostate Cancer and Prostatic Diseases (2021)
-
MR-Guided High-Intensity Directional Ultrasound Ablation of Prostate Cancer
Current Urology Reports (2021)