Prostate Cancer
Focal Therapy – An Evolving Treatment Paradigm for Prostate Cancer Timothy Ito,1
Michael S Borofsky,1 Andrew B Rosenkrantz2 and Samir S Taneja1 1. Division of Urological Oncology, Department of Urology; 2. Department of Radiology, New York University Langone Medical Center
Abstract
Focal therapy for prostate cancer has been proposed as a potential middle ground between active surveillance and radical therapies in patients with clinically localised, low-volume, low-grade disease. Focal therapy with curative intent, aimed at ablating all identified disease, has been agreed upon as an important first step for proof-of-concept. Current consensus also recognises the possibility of use of focal therapy to treat significant disease only while leaving insignificant disease untreated, considerably expanding the number of potential candidates. Transperineal mapping biopsy and multi-parametric magnetic resonance imaging (MRI) currently are the best tools available for mapping disease within the prostate and thus demonstrate the most promise with regards to identifying appropriate candidates for focal therapy. Experience with focal therapeutic modalities, including cryotherapy and high-intensity focused ultrasound (HIFU), has generally been limited to small prospective case series. Preliminary results, however, appear promising, demonstrating good oncological control while limiting morbidity in the form of urinary incontinence and erectile dysfunction. Focal therapy, however, remains experimental at this time, with many challenges to overcome before it can be considered ready for widespread implementation.
Keywords Prostate cancer, focal therapy, index lesion, biopsy, multi-parametric magnetic resonance imaging, cryotherapy, high intensity focused ultrasound
Disclosure: The authors have no conflicts of interest to declare. Acknowledgements: The authors would like to acknowledge the role of the Joseph and Diane Steinberg Charitable Trust in the development of this article. Received: 12 May 2011 Accepted: 27 July 2011 Citation: European Urological Review, 2011;6(2):84–9 Correspondence: Samir S Taneja, 150 East 32nd Street, Suite 200, New York, NY 10016, US. E:
samir.taneja@nyumc.org
Prostate cancer in the prostate-specific antigen (PSA) era has undergone a stage migration, with the majority of patients diagnosed with clinically localised, low-volume, low-grade disease. Current management of prostate cancer is limited to the extremes: active surveillance versus radical therapy. Active surveillance (AS), while feasible given the increasing diagnosis of low-risk, low-volume disease, is underutilised, with only 10 % of men diagnosed with prostate cancer opting to defer therapy.1
Goals of Treatment
Candidate selection is heavily dependent on the goals of treatment. Depending on the ultimate desired oncological outcome, the number and type of potential candidates will vary (see Figure 1).
Radical therapies (e.g. external beam radiation, radical prostatectomy [RP]) offer excellent chance for cure, but carry the burden of significant morbidity in the form of urinary incontinence and erectile dysfunction. Given the predominance of early-stage disease in the PSA era, these therapeutic extremes provide the typical patient diagnosed with prostate cancer today with the quandary of choosing between the significant potential for overtreatment versus ambiguity and the potential for undertreatment.
Focal therapy has been proposed as a middle ground between active surveillance and radical therapies in the management of prostate cancer. Treatment of focally malignant regions of the prostate while leaving normal tissue intact, in concept, provides the opportunity for oncological control while minimising morbidity associated with whole gland therapies. Challenges exist at every step in implementation of effective focal therapy, including patient selection, optimal delivery of therapy and surveillance post therapy. This review examines progress that has been made with each of these challenges, and aims to delineate directions for the future of focal therapy.
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Curative-intent focal therapy seeks complete eradication of disease via selective destruction of a limited region of the prostate and thus requires identification of men with low- to intermediate-risk disease with limited focality as outlined by a recent consensus panel.2
A
recent study by Bott et al. demonstrated that unifocal and unilateral disease in men with low to intermediate pre-operative risk features (PSA ≤20 ng/ml, Gleason score [GS] ≤7, ≤66 % cores positive) existed in only 14 and 13 %, respectively, of men undergoing RP in a contemporary cohort.3
Implementation of
Our group similarly demonstrated in a review
of over 1,400 men undergoing RP that only 11 % had unilateral, low-risk disease (PSA <10 ng/ml, GS <7 and prostate tumour inducer [PTI] <10 %) ideal for curative-intent focal therapy.4
focal therapy in this manner would optimise oncological outcomes but would pertain to a very limited group of men.
The concept of a dominant tumour focus (designated the index lesion) driving malignant potential in prostate cancer has opened the possibility of the use of focal therapy for a broader population, treating significant disease while leaving secondary lesions untreated. Multiple pathological studies have confirmed that the index lesion comprises the vast majority of tumour volume, the highest-grade disease and is the source of most if not all adverse pathological features, including extra-prostatic
© TOUCH BRIEFINGS 2011
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