BERKELEY, CA (UroToday.com) - We have recently published an article on our experience with hemi-ablation high-intensity focused ultrasound to treat unilateral localised prostate cancer. To define unilaterality, we have used a combined localisation strategy based on a complete match between multiparametric MRI and transrectal ultrasound (TRUS) guided systematic biopsy. The goal was to assess feasibility, safety, and short- to medium-term oncological and functional outcomes. Results were promising as hemi-ablation HIFU of an entire lobe, delivered with the intention to treat, was a feasible and safe procedure. Functional and oncological outcomes were also encouraging at 3-years of follow up.
This is a timely issue given the increasing adoption, in surgical practice, of a number of focal therapy energies and modalities to treat focal areas of prostate cancer.[1] Among these therapies, high-intensity focused ultrasound (HIFU) emerged as a valid mini-invasive therapy for localised prostate cancer, using focused ultrasound to generate areas of intense heat to induce tissue necrosis. This energy delivery system, originally used to treat the whole prostate, can technically be used to treat only a part of the gland. The ability of HIFU to achieve thermoablation of targeted prostatic lesions was proven histologically on operative specimens and post-treatment biopsies as well as on MRI imaging.[2, 3, 4] In addition, the International Task Force on Prostate Cancer and the Focal Lesion Paradigm defined tissue-preserving strategy in prostate cancer as the capability to “selectively ablate known disease and preserve existing functions, with the overall objective of minimizing lifetime morbidity without compromising life expectancy.”[5]
While the debate about the role of hemi-ablation HIFU will continue until a randomized trial is conducted, there are clearly benefits to its use that are driving its continued implementation. First, the principle rationale of tissue preservation is harm reduction without compromising cancer control: early self-resolving LUTS were the most common complications. In addition, no rectal toxicities were reported and the strategy was well tolerated in the genitourinary functional domains. The procedure can also be delivered in an ambulatory care setting. This treatment strategy was associated with a good medium-term cancer control in well-selected patients (unilateral low- to intermediate-risk prostate cancer).
Second, tissue preservation leads to functional preservation: all patients were pad-free continent despite a high number of apical lesions, and only 25% of men in our cohort of relatively elderly patients (average age 71 years) who were potent preoperatively reported having erectile dysfunction after hemi-ablation.
Third, much of the debate surrounding hemi-ablation HIFU is its use in cases of poorly differentiated tumour. In our cohort, HIFU performed poorly in patients with a Gleason score ≥8. When we began our study in 2007 there was much disagreement on treating patients with intermediate- and high-risk disease. Some authors have argued that HIFU is a coagulative technology that, unlike radiation therapy, results in complete cell destruction independently of Gleason score. Because we believe in primary cancer control even in high-risk patients and because achieving local control could be difficult with standard therapy and technically possible with HIFU, we had included any Gleason score in our study. We had now changed our mind and our practice because high-grade tumors in prostate cancer are associated with increased neoangiogenesis. This could be responsible of a heat sink phenomenon which is tissue cooling by blood flow that causes thermal loss. The tissue under ablation in high-grade tumor may be inadequately ablated and is a high-risk site for persistent residual progressive disease and metastatic spread.
Fourth, there is no consensus in the literature on whether cancer control in focal therapy should be considered the absence of any cancer or the absence of clinically significant cancer and whether this should be limited to the treated or untreated area. In addition there is no standard follow up protocol for the assessment of clinical failure. In our opinion, histologic confirmation of complete ablation within the treated area appears to be essential in focal therapy. Any positive biopsy in the treated lobe, independently of the percentage of core involvement, should be considered a clinical failure. Instead, contralateral positive biopsy should not be considered as a clinical failure but as a technical limitation. Contralateral disease could be treated by a secondary contralateral hemi-ablation according to the same protocol. A shift to systemic or salvage procedure should be considered, of course, as a treatment failure.
Finally, although PSA testing is accepted as a valid outcome measure in standard therapy, there are no validated biochemical measures in tissue preservation. Furthermore, PSA values are difficult to interpret in the follow up because many factors influence post treatment values (the proportion of initial PSA that was due to tumor, amount of residual prostate tissue, progression of BPH, TURP…). Definitions that are currently used and validated for biochemical failure in whole gland radiation therapy (ASTRO, Phoenix, Stuttgart…) have been used, without any evidence or validation, in whole gland HIFU and focal therapy. Phoenix criteria should not be considered as response criteria to define failure, but as a threshold to offer biopsy. We believe that a specific PSA-based definition is unlikely to be derived and multiparametric MRI will play a major role in the future in the definition of failure if it is validated against histology outcomes.
References:
- M. Valerio, H. U. Ahmed, M. Emberton et al., The role of focal therapy in the management of localised prostate cancer: a systematic review, European Urology, 2013.
- L. Dickinson,Y.Hu,H.U.Ahmed et al., Image-directed, tissue preserving focal therapy of prostate cancer: a feasibility study of a novel deformable magnetic resonance-ultrasound (MR-US) registration system, BJU International, 112(5), 594–601, 2013.
- K. Biermann, R. Montironi, A. Lopez-Beltran, S. Zhang, and L. Cheng, Histopathological findings after treatment of prostate cancer using high-intensity focused ultrasound (HIFU), Prostate, 70(11), 1196–1200, 2010.
- P. Ryan, A. Finelli, N. Lawrentschuk et al., Prostatic needle biopsies following primary high-intensity focused ultrasound (HIFU) therapy for prostatic adenocarcinoma: histopathological features in tumour and non-tumour tissue, Journal of Clinical Pathology, Vol. 65, 729–734, 2012.
- R. Turpen and C. J. Rosser, Focal therapy for prostate cancer: revolution or evolution? BMC Urology, 9(1) article 2, 2009.
Written by:
Aoun Fouad, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Department of Urology, Jules Bordet Institute, 1 Héger-Bordet Street, 1000 Brussels, Belgium; Université Libre de Bruxelles, 50 Franklin Roosevelt Avenue, 1050 Brussels, Belgium
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