Systematic Review of the Efficacy and Safety of High-Intensity Focussed Ultrasound for the Primary and Salvage Treatment of Prostate Cancer

European Urology

Volume 58, issue 6, pages e53-e62, December 2010

Prostate Cancer

Systematic Review of the Efficacy and Safety of High-Intensity Focussed Ultrasound for the Primary and Salvage Treatment of Prostate Cancer

Marisa Warmuth, Tim Johansson and Philipp Mad

Accepted 6 September 2010, Published online 15 September 2010, pages 803 - 815

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3. Evidence synthesis

Fig. 1 shows the detailed literature selection process. We identified and included 20 studies that met our inclusion criteria, all of which were prospective case series. We were not able to identify any prospective (randomised) controlled trials in our literature search. Because all the studies were conducted in an uncontrolled manner, we downgraded them from low quality to very low quality. Further factors lowering the quality of evidence also applied, such as the high likelihood of publication bias or the lack of precise data.

Fig. 1 Literature selection process (PRISMA flow diagram).PICOS = Population, Intervention, Control, Outcome, Study design; PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

References in context

Fig. 1 shows the detailed literature selection process.
Go to context

In all studies included in our review, 3018 patients were treated with HIFU, of whom 2794 (93%) underwent HIFU for primary therapy 17 x Ahmed HU, Zacharakis E, Dudderidge T, et al. High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series. Br J Cancer 2009 7;101:19–26. , 18 x A. Blana, F.J. Murat, B. Walter, et al. First analysis of the long-term results with transrectal HIFU in patients with localised prostate cancer. Eur Urol. 2008;53:1194-1203 Abstract, Full-text, PDF, Crossref. , 19 x A. Blana, B. Walter, S. Rogenhofer, W.F. Wieland. High-intensity focused ultrasound for the treatment of localized prostate cancer: 5-year experience. Urology. 2004;63:297-300 Crossref. , 20 x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. Results and side effects of high-intensity focused ultrasound in localized prostate cancer. J Endourol. 2001;15:437-440 discussion 447–8 Crossref. , 21 x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. The status of high-intensity focused ultrasound in the treatment of localized prostate cancer and the impact of a combined resection. Curr Urol Rep. 2003;4:248-252 Crossref. , 22 x C.G. Chaussy, S. Thüroff, C.G. Chaussy, S. Thüroff. High-intensive focused ultrasound in localized prostate cancer. J Endourol. 2000;14:293-299 Crossref. , 23 x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high intensity focused ultrasound for the treatment of localized prostate cancer: factors influencing the outcome. Eur Urol. 2001;40:124-129 Crossref. , 24 x H.M. Lee, J.H. Hong, H.Y. Choi, H.M. Lee, J.H. Hong, H.Y. Choi. High-intensity focused ultrasound therapy for clinically localized prostate cancer. Prostate Cancer Prostatic Dis. 2006;9:439-443 Crossref. , 25 x L. Mearini, L. D’Urso, D. Collura, et al. Visually directed transrectal high intensity focused ultrasound for the treatment of prostate cancer: a preliminary report on the Italian experience. J Urol. 2009;181:105-111 discussion 111–2 , 26 x S. Muto, T. Yoshii, K. Saito, et al. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn J Clin Oncol. 2008;38:192-199 Crossref. , 27 x L. Poissonnier, J.-Y. Chapelon, O. Rouvière, et al. Control of prostate cancer by transrectal HIFU in 227 patients. Eur Urol. 2007;51:381-387 Abstract, Full-text, PDF, Crossref. , 28 x S. Thüroff, C. Chaussy, G. Vallancien, et al. High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study. J Endourol. 2003;17:673-677 , 29 x T. Uchida, S. Baba, A. Irie, et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study. Hinyokika Kiyo. 2005;51:651-658 , 30 x T. Uchida, H. Ohkusa, Y. Nagata, et al. Treatment of localized prostate cancer using high-intensity focused ultrasound. BJU Int. 2006;97:56-61 Crossref. , 31 x T. Uchida, H. Ohkusa, H. Yamashita, et al. Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer. Int J Urol. 2006;13:228-233 Crossref. , 32 x T. Uchida, S. Shoji, M. Nakano, et al. Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: eight-year experience. Int J Urol. 2009;16:881-886 Crossref. , and 33 x B. Walter, S. Rogenhofer, W.F. Wieland, A. Blana. Combination from TUR-P and high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer—experience with 70 patients. J Urologie Urogynakologie. 2004;11:5-10 and the remaining 227 (7%) underwent salvage HIFU 34 x M. Colombel, L. Poissonnier, X. Martin, A. Gelet. Clinical results of the prostate HIFU project. Eur Urol Suppl. 2006;5:491-494 Abstract, Full-text, PDF, Crossref. , 35 x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high-intensity focused ultrasound: minimally invasive therapy of localized prostate cancer [published correction appears in J Endourol 2000;14:697]. J Endourol. 2000;14:519-528 Crossref. , and 36 x A. Gelet, J.Y. Chapelon, L. Poissonnier, et al. Local recurrence of prostate cancer after external beam radiotherapy: early experience of salvage therapy using high-intensity focused ultrasonography. Urology. 2004;63:625-629 Crossref. . Most patients (56%) undergoing HIFU for primary therapy were treated with the Ablatherm device 18 x A. Blana, F.J. Murat, B. Walter, et al. First analysis of the long-term results with transrectal HIFU in patients with localised prostate cancer. Eur Urol. 2008;53:1194-1203 Abstract, Full-text, PDF, Crossref. , 19 x A. Blana, B. Walter, S. Rogenhofer, W.F. Wieland. High-intensity focused ultrasound for the treatment of localized prostate cancer: 5-year experience. Urology. 2004;63:297-300 Crossref. , 21 x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. The status of high-intensity focused ultrasound in the treatment of localized prostate cancer and the impact of a combined resection. Curr Urol Rep. 2003;4:248-252 Crossref. , 24 x H.M. Lee, J.H. Hong, H.Y. Choi, H.M. Lee, J.H. Hong, H.Y. Choi. High-intensity focused ultrasound therapy for clinically localized prostate cancer. Prostate Cancer Prostatic Dis. 2006;9:439-443 Crossref. , 27 x L. Poissonnier, J.-Y. Chapelon, O. Rouvière, et al. Control of prostate cancer by transrectal HIFU in 227 patients. Eur Urol. 2007;51:381-387 Abstract, Full-text, PDF, Crossref. , 28 x S. Thüroff, C. Chaussy, G. Vallancien, et al. High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study. J Endourol. 2003;17:673-677 , 33 x B. Walter, S. Rogenhofer, W.F. Wieland, A. Blana. Combination from TUR-P and high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer—experience with 70 patients. J Urologie Urogynakologie. 2004;11:5-10 , and 34 x M. Colombel, L. Poissonnier, X. Martin, A. Gelet. Clinical results of the prostate HIFU project. Eur Urol Suppl. 2006;5:491-494 Abstract, Full-text, PDF, Crossref. ; 44% were treated with the Sonablate device 17 x Ahmed HU, Zacharakis E, Dudderidge T, et al. High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series. Br J Cancer 2009 7;101:19–26. , 25 x L. Mearini, L. D’Urso, D. Collura, et al. Visually directed transrectal high intensity focused ultrasound for the treatment of prostate cancer: a preliminary report on the Italian experience. J Urol. 2009;181:105-111 discussion 111–2 , 26 x S. Muto, T. Yoshii, K. Saito, et al. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn J Clin Oncol. 2008;38:192-199 Crossref. , 29 x T. Uchida, S. Baba, A. Irie, et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study. Hinyokika Kiyo. 2005;51:651-658 , 30 x T. Uchida, H. Ohkusa, Y. Nagata, et al. Treatment of localized prostate cancer using high-intensity focused ultrasound. BJU Int. 2006;97:56-61 Crossref. , 31 x T. Uchida, H. Ohkusa, H. Yamashita, et al. Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer. Int J Urol. 2006;13:228-233 Crossref. , and 32 x T. Uchida, S. Shoji, M. Nakano, et al. Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: eight-year experience. Int J Urol. 2009;16:881-886 Crossref. . All salvage HIFU treatments were conducted with the Ablatherm device 34 x M. Colombel, L. Poissonnier, X. Martin, A. Gelet. Clinical results of the prostate HIFU project. Eur Urol Suppl. 2006;5:491-494 Abstract, Full-text, PDF, Crossref. , 35 x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high-intensity focused ultrasound: minimally invasive therapy of localized prostate cancer [published correction appears in J Endourol 2000;14:697]. J Endourol. 2000;14:519-528 Crossref. , and 36 x A. Gelet, J.Y. Chapelon, L. Poissonnier, et al. Local recurrence of prostate cancer after external beam radiotherapy: early experience of salvage therapy using high-intensity focused ultrasonography. Urology. 2004;63:625-629 Crossref. . Adverse events concerned the urinary tract (1–58%) 17 x Ahmed HU, Zacharakis E, Dudderidge T, et al. High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series. Br J Cancer 2009 7;101:19–26. , 18 x A. Blana, F.J. Murat, B. Walter, et al. First analysis of the long-term results with transrectal HIFU in patients with localised prostate cancer. Eur Urol. 2008;53:1194-1203 Abstract, Full-text, PDF, Crossref. , 19 x A. Blana, B. Walter, S. Rogenhofer, W.F. Wieland. High-intensity focused ultrasound for the treatment of localized prostate cancer: 5-year experience. Urology. 2004;63:297-300 Crossref. , 20 x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. Results and side effects of high-intensity focused ultrasound in localized prostate cancer. J Endourol. 2001;15:437-440 discussion 447–8 Crossref. , 21 x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. The status of high-intensity focused ultrasound in the treatment of localized prostate cancer and the impact of a combined resection. Curr Urol Rep. 2003;4:248-252 Crossref. , 22 x C.G. Chaussy, S. Thüroff, C.G. Chaussy, S. Thüroff. High-intensive focused ultrasound in localized prostate cancer. J Endourol. 2000;14:293-299 Crossref. , 23 x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high intensity focused ultrasound for the treatment of localized prostate cancer: factors influencing the outcome. Eur Urol. 2001;40:124-129 Crossref. , 24 x H.M. Lee, J.H. Hong, H.Y. Choi, H.M. Lee, J.H. Hong, H.Y. Choi. High-intensity focused ultrasound therapy for clinically localized prostate cancer. Prostate Cancer Prostatic Dis. 2006;9:439-443 Crossref. , 25 x L. Mearini, L. D’Urso, D. Collura, et al. Visually directed transrectal high intensity focused ultrasound for the treatment of prostate cancer: a preliminary report on the Italian experience. J Urol. 2009;181:105-111 discussion 111–2 , 26 x S. Muto, T. Yoshii, K. Saito, et al. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn J Clin Oncol. 2008;38:192-199 Crossref. , 27 x L. Poissonnier, J.-Y. Chapelon, O. Rouvière, et al. Control of prostate cancer by transrectal HIFU in 227 patients. Eur Urol. 2007;51:381-387 Abstract, Full-text, PDF, Crossref. , 28 x S. Thüroff, C. Chaussy, G. Vallancien, et al. High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study. J Endourol. 2003;17:673-677 , 29 x T. Uchida, S. Baba, A. Irie, et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study. Hinyokika Kiyo. 2005;51:651-658 , 30 x T. Uchida, H. Ohkusa, Y. Nagata, et al. Treatment of localized prostate cancer using high-intensity focused ultrasound. BJU Int. 2006;97:56-61 Crossref. , 31 x T. Uchida, H. Ohkusa, H. Yamashita, et al. Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer. Int J Urol. 2006;13:228-233 Crossref. , 32 x T. Uchida, S. Shoji, M. Nakano, et al. Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: eight-year experience. Int J Urol. 2009;16:881-886 Crossref. , 33 x B. Walter, S. Rogenhofer, W.F. Wieland, A. Blana. Combination from TUR-P and high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer—experience with 70 patients. J Urologie Urogynakologie. 2004;11:5-10 , 34 x M. Colombel, L. Poissonnier, X. Martin, A. Gelet. Clinical results of the prostate HIFU project. Eur Urol Suppl. 2006;5:491-494 Abstract, Full-text, PDF, Crossref. , 35 x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high-intensity focused ultrasound: minimally invasive therapy of localized prostate cancer [published correction appears in J Endourol 2000;14:697]. J Endourol. 2000;14:519-528 Crossref. , and 36 x A. Gelet, J.Y. Chapelon, L. Poissonnier, et al. Local recurrence of prostate cancer after external beam radiotherapy: early experience of salvage therapy using high-intensity focused ultrasonography. Urology. 2004;63:625-629 Crossref. , potency (1–77%) 17 x Ahmed HU, Zacharakis E, Dudderidge T, et al. High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series. Br J Cancer 2009 7;101:19–26. , 18 x A. Blana, F.J. Murat, B. Walter, et al. First analysis of the long-term results with transrectal HIFU in patients with localised prostate cancer. Eur Urol. 2008;53:1194-1203 Abstract, Full-text, PDF, Crossref. , 19 x A. Blana, B. Walter, S. Rogenhofer, W.F. Wieland. High-intensity focused ultrasound for the treatment of localized prostate cancer: 5-year experience. Urology. 2004;63:297-300 Crossref. , 20 x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. Results and side effects of high-intensity focused ultrasound in localized prostate cancer. J Endourol. 2001;15:437-440 discussion 447–8 Crossref. , 21 x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. The status of high-intensity focused ultrasound in the treatment of localized prostate cancer and the impact of a combined resection. Curr Urol Rep. 2003;4:248-252 Crossref. , 23 x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high intensity focused ultrasound for the treatment of localized prostate cancer: factors influencing the outcome. Eur Urol. 2001;40:124-129 Crossref. , 27 x L. Poissonnier, J.-Y. Chapelon, O. Rouvière, et al. Control of prostate cancer by transrectal HIFU in 227 patients. Eur Urol. 2007;51:381-387 Abstract, Full-text, PDF, Crossref. , 28 x S. Thüroff, C. Chaussy, G. Vallancien, et al. High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study. J Endourol. 2003;17:673-677 , 29 x T. Uchida, S. Baba, A. Irie, et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study. Hinyokika Kiyo. 2005;51:651-658 , 30 x T. Uchida, H. Ohkusa, Y. Nagata, et al. Treatment of localized prostate cancer using high-intensity focused ultrasound. BJU Int. 2006;97:56-61 Crossref. , 31 x T. Uchida, H. Ohkusa, H. Yamashita, et al. Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer. Int J Urol. 2006;13:228-233 Crossref. , 32 x T. Uchida, S. Shoji, M. Nakano, et al. Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: eight-year experience. Int J Urol. 2009;16:881-886 Crossref. , 33 x B. Walter, S. Rogenhofer, W.F. Wieland, A. Blana. Combination from TUR-P and high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer—experience with 70 patients. J Urologie Urogynakologie. 2004;11:5-10 , and 35 x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high-intensity focused ultrasound: minimally invasive therapy of localized prostate cancer [published correction appears in J Endourol 2000;14:697]. J Endourol. 2000;14:519-528 Crossref. , the rectum (0–15%) 17 x Ahmed HU, Zacharakis E, Dudderidge T, et al. High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series. Br J Cancer 2009 7;101:19–26. , 19 x A. Blana, B. Walter, S. Rogenhofer, W.F. Wieland. High-intensity focused ultrasound for the treatment of localized prostate cancer: 5-year experience. Urology. 2004;63:297-300 Crossref. , 20 x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. Results and side effects of high-intensity focused ultrasound in localized prostate cancer. J Endourol. 2001;15:437-440 discussion 447–8 Crossref. , 22 x C.G. Chaussy, S. Thüroff, C.G. Chaussy, S. Thüroff. High-intensive focused ultrasound in localized prostate cancer. J Endourol. 2000;14:293-299 Crossref. , 23 x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high intensity focused ultrasound for the treatment of localized prostate cancer: factors influencing the outcome. Eur Urol. 2001;40:124-129 Crossref. , 25 x L. Mearini, L. D’Urso, D. Collura, et al. Visually directed transrectal high intensity focused ultrasound for the treatment of prostate cancer: a preliminary report on the Italian experience. J Urol. 2009;181:105-111 discussion 111–2 , 28 x S. Thüroff, C. Chaussy, G. Vallancien, et al. High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study. J Endourol. 2003;17:673-677 , 30 x T. Uchida, H. Ohkusa, Y. Nagata, et al. Treatment of localized prostate cancer using high-intensity focused ultrasound. BJU Int. 2006;97:56-61 Crossref. , 31 x T. Uchida, H. Ohkusa, H. Yamashita, et al. Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer. Int J Urol. 2006;13:228-233 Crossref. , 32 x T. Uchida, S. Shoji, M. Nakano, et al. Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: eight-year experience. Int J Urol. 2009;16:881-886 Crossref. , 33 x B. Walter, S. Rogenhofer, W.F. Wieland, A. Blana. Combination from TUR-P and high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer—experience with 70 patients. J Urologie Urogynakologie. 2004;11:5-10 , 35 x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high-intensity focused ultrasound: minimally invasive therapy of localized prostate cancer [published correction appears in J Endourol 2000;14:697]. J Endourol. 2000;14:519-528 Crossref. , and 36 x A. Gelet, J.Y. Chapelon, L. Poissonnier, et al. Local recurrence of prostate cancer after external beam radiotherapy: early experience of salvage therapy using high-intensity focused ultrasonography. Urology. 2004;63:625-629 Crossref. , and pain (1–6%) 18 x A. Blana, F.J. Murat, B. Walter, et al. First analysis of the long-term results with transrectal HIFU in patients with localised prostate cancer. Eur Urol. 2008;53:1194-1203 Abstract, Full-text, PDF, Crossref. , 19 x A. Blana, B. Walter, S. Rogenhofer, W.F. Wieland. High-intensity focused ultrasound for the treatment of localized prostate cancer: 5-year experience. Urology. 2004;63:297-300 Crossref. , 23 x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high intensity focused ultrasound for the treatment of localized prostate cancer: factors influencing the outcome. Eur Urol. 2001;40:124-129 Crossref. , 27 x L. Poissonnier, J.-Y. Chapelon, O. Rouvière, et al. Control of prostate cancer by transrectal HIFU in 227 patients. Eur Urol. 2007;51:381-387 Abstract, Full-text, PDF, Crossref. , 33 x B. Walter, S. Rogenhofer, W.F. Wieland, A. Blana. Combination from TUR-P and high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer—experience with 70 patients. J Urologie Urogynakologie. 2004;11:5-10 , 34 x M. Colombel, L. Poissonnier, X. Martin, A. Gelet. Clinical results of the prostate HIFU project. Eur Urol Suppl. 2006;5:491-494 Abstract, Full-text, PDF, Crossref. , and 35 x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high-intensity focused ultrasound: minimally invasive therapy of localized prostate cancer [published correction appears in J Endourol 2000;14:697]. J Endourol. 2000;14:519-528 Crossref. . Patient-relevant outcomes such as quality of life were assessed using validated questionnaires. However, these scores either changed little from pre- to post-HIFU treatment or yielded controversial results 17 x Ahmed HU, Zacharakis E, Dudderidge T, et al. High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series. Br J Cancer 2009 7;101:19–26. , 19 x A. Blana, B. Walter, S. Rogenhofer, W.F. Wieland. High-intensity focused ultrasound for the treatment of localized prostate cancer: 5-year experience. Urology. 2004;63:297-300 Crossref. , 20 x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. Results and side effects of high-intensity focused ultrasound in localized prostate cancer. J Endourol. 2001;15:437-440 discussion 447–8 Crossref. , 21 x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. The status of high-intensity focused ultrasound in the treatment of localized prostate cancer and the impact of a combined resection. Curr Urol Rep. 2003;4:248-252 Crossref. , 25 x L. Mearini, L. D’Urso, D. Collura, et al. Visually directed transrectal high intensity focused ultrasound for the treatment of prostate cancer: a preliminary report on the Italian experience. J Urol. 2009;181:105-111 discussion 111–2 , 26 x S. Muto, T. Yoshii, K. Saito, et al. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn J Clin Oncol. 2008;38:192-199 Crossref. , 29 x T. Uchida, S. Baba, A. Irie, et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study. Hinyokika Kiyo. 2005;51:651-658 , and 33 x B. Walter, S. Rogenhofer, W.F. Wieland, A. Blana. Combination from TUR-P and high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer—experience with 70 patients. J Urologie Urogynakologie. 2004;11:5-10 . For all HIFU procedures, the biochemical disease-free survival rate was between 78% and 84%, 0% and 91%, 20% and 86%, 45% and 84%, and 69% at 1, 2, 3, 5, and 7 yr, respectively 18 x A. Blana, F.J. Murat, B. Walter, et al. First analysis of the long-term results with transrectal HIFU in patients with localised prostate cancer. Eur Urol. 2008;53:1194-1203 Abstract, Full-text, PDF, Crossref. , 25 x L. Mearini, L. D’Urso, D. Collura, et al. Visually directed transrectal high intensity focused ultrasound for the treatment of prostate cancer: a preliminary report on the Italian experience. J Urol. 2009;181:105-111 discussion 111–2 , 26 x S. Muto, T. Yoshii, K. Saito, et al. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn J Clin Oncol. 2008;38:192-199 Crossref. , 27 x L. Poissonnier, J.-Y. Chapelon, O. Rouvière, et al. Control of prostate cancer by transrectal HIFU in 227 patients. Eur Urol. 2007;51:381-387 Abstract, Full-text, PDF, Crossref. , 29 x T. Uchida, S. Baba, A. Irie, et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study. Hinyokika Kiyo. 2005;51:651-658 , 30 x T. Uchida, H. Ohkusa, Y. Nagata, et al. Treatment of localized prostate cancer using high-intensity focused ultrasound. BJU Int. 2006;97:56-61 Crossref. , 31 x T. Uchida, H. Ohkusa, H. Yamashita, et al. Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer. Int J Urol. 2006;13:228-233 Crossref. , and 32 x T. Uchida, S. Shoji, M. Nakano, et al. Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: eight-year experience. Int J Urol. 2009;16:881-886 Crossref. . The negative biopsy rate was 86% at 3 mo and 80% at 15 mo 18 x A. Blana, F.J. Murat, B. Walter, et al. First analysis of the long-term results with transrectal HIFU in patients with localised prostate cancer. Eur Urol. 2008;53:1194-1203 Abstract, Full-text, PDF, Crossref. , 19 x A. Blana, B. Walter, S. Rogenhofer, W.F. Wieland. High-intensity focused ultrasound for the treatment of localized prostate cancer: 5-year experience. Urology. 2004;63:297-300 Crossref. , 20 x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. Results and side effects of high-intensity focused ultrasound in localized prostate cancer. J Endourol. 2001;15:437-440 discussion 447–8 Crossref. , 21 x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. The status of high-intensity focused ultrasound in the treatment of localized prostate cancer and the impact of a combined resection. Curr Urol Rep. 2003;4:248-252 Crossref. , 22 x C.G. Chaussy, S. Thüroff, C.G. Chaussy, S. Thüroff. High-intensive focused ultrasound in localized prostate cancer. J Endourol. 2000;14:293-299 Crossref. , 23 x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high intensity focused ultrasound for the treatment of localized prostate cancer: factors influencing the outcome. Eur Urol. 2001;40:124-129 Crossref. , 25 x L. Mearini, L. D’Urso, D. Collura, et al. Visually directed transrectal high intensity focused ultrasound for the treatment of prostate cancer: a preliminary report on the Italian experience. J Urol. 2009;181:105-111 discussion 111–2 , 26 x S. Muto, T. Yoshii, K. Saito, et al. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn J Clin Oncol. 2008;38:192-199 Crossref. , 27 x L. Poissonnier, J.-Y. Chapelon, O. Rouvière, et al. Control of prostate cancer by transrectal HIFU in 227 patients. Eur Urol. 2007;51:381-387 Abstract, Full-text, PDF, Crossref. , 28 x S. Thüroff, C. Chaussy, G. Vallancien, et al. High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study. J Endourol. 2003;17:673-677 , 29 x T. Uchida, S. Baba, A. Irie, et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study. Hinyokika Kiyo. 2005;51:651-658 , 30 x T. Uchida, H. Ohkusa, Y. Nagata, et al. Treatment of localized prostate cancer using high-intensity focused ultrasound. BJU Int. 2006;97:56-61 Crossref. , 32 x T. Uchida, S. Shoji, M. Nakano, et al. Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: eight-year experience. Int J Urol. 2009;16:881-886 Crossref. , 33 x B. Walter, S. Rogenhofer, W.F. Wieland, A. Blana. Combination from TUR-P and high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer—experience with 70 patients. J Urologie Urogynakologie. 2004;11:5-10 , 34 x M. Colombel, L. Poissonnier, X. Martin, A. Gelet. Clinical results of the prostate HIFU project. Eur Urol Suppl. 2006;5:491-494 Abstract, Full-text, PDF, Crossref. , 35 x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high-intensity focused ultrasound: minimally invasive therapy of localized prostate cancer [published correction appears in J Endourol 2000;14:697]. J Endourol. 2000;14:519-528 Crossref. , and 36 x A. Gelet, J.Y. Chapelon, L. Poissonnier, et al. Local recurrence of prostate cancer after external beam radiotherapy: early experience of salvage therapy using high-intensity focused ultrasonography. Urology. 2004;63:625-629 Crossref. . Overall survival rate and prostate-cancer specific survival rate were only reported in 1 of 20 studies and were 90% and 100% at 5 yr and 83% and 98% at 8 yr, respectively [18] x A. Blana, F.J. Murat, B. Walter, et al. First analysis of the long-term results with transrectal HIFU in patients with localised prostate cancer. Eur Urol. 2008;53:1194-1203 Abstract, Full-text, PDF, Crossref. .

3.1. Ablatherm high-intensity focussed ultrasound

3.1.1. Primary therapy

We identified 11 case series assessing Ablatherm HIFU as a primary therapy option in prostate cancer, which were conducted by four study groups in Germany, France, and the Republic of Korea 18 x A. Blana, F.J. Murat, B. Walter, et al. First analysis of the long-term results with transrectal HIFU in patients with localised prostate cancer. Eur Urol. 2008;53:1194-1203 Abstract, Full-text, PDF, Crossref. , 19 x A. Blana, B. Walter, S. Rogenhofer, W.F. Wieland. High-intensity focused ultrasound for the treatment of localized prostate cancer: 5-year experience. Urology. 2004;63:297-300 Crossref. , 20 x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. Results and side effects of high-intensity focused ultrasound in localized prostate cancer. J Endourol. 2001;15:437-440 discussion 447–8 Crossref. , 21 x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. The status of high-intensity focused ultrasound in the treatment of localized prostate cancer and the impact of a combined resection. Curr Urol Rep. 2003;4:248-252 Crossref. , 22 x C.G. Chaussy, S. Thüroff, C.G. Chaussy, S. Thüroff. High-intensive focused ultrasound in localized prostate cancer. J Endourol. 2000;14:293-299 Crossref. , 23 x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high intensity focused ultrasound for the treatment of localized prostate cancer: factors influencing the outcome. Eur Urol. 2001;40:124-129 Crossref. , 24 x H.M. Lee, J.H. Hong, H.Y. Choi, H.M. Lee, J.H. Hong, H.Y. Choi. High-intensity focused ultrasound therapy for clinically localized prostate cancer. Prostate Cancer Prostatic Dis. 2006;9:439-443 Crossref. , 27 x L. Poissonnier, J.-Y. Chapelon, O. Rouvière, et al. Control of prostate cancer by transrectal HIFU in 227 patients. Eur Urol. 2007;51:381-387 Abstract, Full-text, PDF, Crossref. , 28 x S. Thüroff, C. Chaussy, G. Vallancien, et al. High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study. J Endourol. 2003;17:673-677 , 33 x B. Walter, S. Rogenhofer, W.F. Wieland, A. Blana. Combination from TUR-P and high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer—experience with 70 patients. J Urologie Urogynakologie. 2004;11:5-10 , and 34 x M. Colombel, L. Poissonnier, X. Martin, A. Gelet. Clinical results of the prostate HIFU project. Eur Urol Suppl. 2006;5:491-494 Abstract, Full-text, PDF, Crossref. . Study characteristics are shown in Table 3. Between 58 and 402 patients with localised prostate cancer (T1–T2, N0–Nx, M0) with a mean age of 66–72 yr were treated with HIFU. In 4 of 11 case series, patients were recruited consecutively 19 x A. Blana, B. Walter, S. Rogenhofer, W.F. Wieland. High-intensity focused ultrasound for the treatment of localized prostate cancer: 5-year experience. Urology. 2004;63:297-300 Crossref. , 23 x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high intensity focused ultrasound for the treatment of localized prostate cancer: factors influencing the outcome. Eur Urol. 2001;40:124-129 Crossref. , 27 x L. Poissonnier, J.-Y. Chapelon, O. Rouvière, et al. Control of prostate cancer by transrectal HIFU in 227 patients. Eur Urol. 2007;51:381-387 Abstract, Full-text, PDF, Crossref. , and 33 x B. Walter, S. Rogenhofer, W.F. Wieland, A. Blana. Combination from TUR-P and high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer—experience with 70 patients. J Urologie Urogynakologie. 2004;11:5-10 . The mean preoperative PSA level was 7–12 ng/ml, Gleason score was ≤7 in most patients, and the mean preoperative prostate volume was 21–37 ml. Between 0% and 43% of men received neoadjuvant androgen-deprivation therapy (ADT), and 65–100% of patients underwent transurethral resection of the prostate (TURP) before or in combination with HIFU. Patients received between one and three HIFU treatments; most patients (57–96%) underwent one treatment. The mean follow-up period varied between 6 and 77 mo.

Table 3 Ablatherm high-intensity focussed ultrasound: primary therapy

Study	Blana et al [18] x A. Blana, F.J. Murat, B. Walter, et al. First analysis of the long-term results with transrectal HIFU in patients with localised prostate cancer. Eur Urol. 2008;53:1194-1203 Abstract, Full-text, PDF, Crossref.	Poissonnier et al [27] x L. Poissonnier, J.-Y. Chapelon, O. Rouvière, et al. Control of prostate cancer by transrectal HIFU in 227 patients. Eur Urol. 2007;51:381-387 Abstract, Full-text, PDF, Crossref.	Colombel et al [34] x M. Colombel, L. Poissonnier, X. Martin, A. Gelet. Clinical results of the prostate HIFU project. Eur Urol Suppl. 2006;5:491-494 Abstract, Full-text, PDF, Crossref.	Lee et al [24] x H.M. Lee, J.H. Hong, H.Y. Choi, H.M. Lee, J.H. Hong, H.Y. Choi. High-intensity focused ultrasound therapy for clinically localized prostate cancer. Prostate Cancer Prostatic Dis. 2006;9:439-443 Crossref.	Blana et al [19] x A. Blana, B. Walter, S. Rogenhofer, W.F. Wieland. High-intensity focused ultrasound for the treatment of localized prostate cancer: 5-year experience. Urology. 2004;63:297-300 Crossref.	Walter et al [33] x B. Walter, S. Rogenhofer, W.F. Wieland, A. Blana. Combination from TUR-P and high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer—experience with 70 patients. J Urologie Urogynakologie. 2004;11:5-10	Chaussy et al [21] x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. The status of high-intensity focused ultrasound in the treatment of localized prostate cancer and the impact of a combined resection. Curr Urol Rep. 2003;4:248-252 Crossref.	Thüroff et al [28] x S. Thüroff, C. Chaussy, G. Vallancien, et al. High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study. J Endourol. 2003;17:673-677	Chaussy et al [20] x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. Results and side effects of high-intensity focused ultrasound in localized prostate cancer. J Endourol. 2001;15:437-440 discussion 447–8 Crossref.	Gelet et al [23] x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high intensity focused ultrasound for the treatment of localized prostate cancer: factors influencing the outcome. Eur Urol. 2001;40:124-129 Crossref.	Chaussy et al [22] x C.G. Chaussy, S. Thüroff, C.G. Chaussy, S. Thüroff. High-intensive focused ultrasound in localized prostate cancer. J Endourol. 2000;14:293-299 Crossref.
Country	DE/FR: 2 centres	FR	FR	KR	DE	DE	DE	DE/FR/NL: 6 centres	DE	FR	DE
Patients, No.	140	227	242	58	146	70	271 (A: prospective: HIFU 96; B: retrospective: TURP + HIFU 175)	402	184	102	65 (A: global, n = NA vs B: selective treatment, n = NA)
Patients, age, yr (range)	M: 70 (45–87)	Ø 69 ± 6	Ø 71 ± 6	Ø 70 ± 6	Ø 70 ± 7	Ø 67 ± 6	A: Ø 66 ± 8; B: Ø 68 ± 7	Ø 70 ± 7	Ø 72 (59–81)	Ø 71 ± 6	NA
Tumour stage	T1a–T2cNxM0	T1–T2	T1cT2	T1–T2	T1–T2N0M0	T1–T2bN0M0	T1–T2c	T1–T2N0-NxM0	T1–T2NxM0	T1b–T2	Localised
Neoadjuvant ADT, % of pts	16	33	NA	29	43	NA	NA	0	NA	8	NA
TURP prior to/combined with HIFU, % of pts	NA	78	100	91	NA	100	65	NA	NA	NA	NA
Follow-up, mo (range)	Ø 77 ± 12	Ø 28 ± 20; M: 21 (12–107)	NA	Ø 14 ± 4	Ø 23 (4–62)	Ø 15 ± 7	A: Ø 19 ± 12, B: Ø 11 ± 6	Ø 14 (0–51)	Ø 6, M: 4 (0–30)	Ø 19 (3–76)	Ø 10 (1–18)

ADT = androgen-deprivation therapy; DE = Germany; FR = France; HIFU = high-intensity focussed ultrasound; KR = Republic of Korea; M = median; NA = not available; NL = Netherlands; Ø = mean plus or minus standard deviation; pts = patients; TURP = transurethral resection of the prostate.

References in context

Study characteristics are shown in Table 3.
Go to context

Table 4 shows the evidence profile of Ablatherm HIFU as a primary therapy option in prostate cancer. The biochemical disease-free survival rate was 66% and 77% after 5 yr 18 x A. Blana, F.J. Murat, B. Walter, et al. First analysis of the long-term results with transrectal HIFU in patients with localised prostate cancer. Eur Urol. 2008;53:1194-1203 Abstract, Full-text, PDF, Crossref. , and 27 x L. Poissonnier, J.-Y. Chapelon, O. Rouvière, et al. Control of prostate cancer by transrectal HIFU in 227 patients. Eur Urol. 2007;51:381-387 Abstract, Full-text, PDF, Crossref. and 69% after 7 yr [18] x A. Blana, F.J. Murat, B. Walter, et al. First analysis of the long-term results with transrectal HIFU in patients with localised prostate cancer. Eur Urol. 2008;53:1194-1203 Abstract, Full-text, PDF, Crossref. . The negative biopsy rate was assessed in all but one study and varied between 65% and 94% 18 x A. Blana, F.J. Murat, B. Walter, et al. First analysis of the long-term results with transrectal HIFU in patients with localised prostate cancer. Eur Urol. 2008;53:1194-1203 Abstract, Full-text, PDF, Crossref. , 19 x A. Blana, B. Walter, S. Rogenhofer, W.F. Wieland. High-intensity focused ultrasound for the treatment of localized prostate cancer: 5-year experience. Urology. 2004;63:297-300 Crossref. , 20 x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. Results and side effects of high-intensity focused ultrasound in localized prostate cancer. J Endourol. 2001;15:437-440 discussion 447–8 Crossref. , 21 x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. The status of high-intensity focused ultrasound in the treatment of localized prostate cancer and the impact of a combined resection. Curr Urol Rep. 2003;4:248-252 Crossref. , 22 x C.G. Chaussy, S. Thüroff, C.G. Chaussy, S. Thüroff. High-intensive focused ultrasound in localized prostate cancer. J Endourol. 2000;14:293-299 Crossref. , 23 x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high intensity focused ultrasound for the treatment of localized prostate cancer: factors influencing the outcome. Eur Urol. 2001;40:124-129 Crossref. , 27 x L. Poissonnier, J.-Y. Chapelon, O. Rouvière, et al. Control of prostate cancer by transrectal HIFU in 227 patients. Eur Urol. 2007;51:381-387 Abstract, Full-text, PDF, Crossref. , 28 x S. Thüroff, C. Chaussy, G. Vallancien, et al. High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study. J Endourol. 2003;17:673-677 , 33 x B. Walter, S. Rogenhofer, W.F. Wieland, A. Blana. Combination from TUR-P and high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer—experience with 70 patients. J Urologie Urogynakologie. 2004;11:5-10 , and 34 x M. Colombel, L. Poissonnier, X. Martin, A. Gelet. Clinical results of the prostate HIFU project. Eur Urol Suppl. 2006;5:491-494 Abstract, Full-text, PDF, Crossref. ; the point in time of biopsy was not specified. In one case series the negative biopsy rate was 86% at 3 mo [34] x M. Colombel, L. Poissonnier, X. Martin, A. Gelet. Clinical results of the prostate HIFU project. Eur Urol Suppl. 2006;5:491-494 Abstract, Full-text, PDF, Crossref. .

Table 4 Evidence profile: Ablatherm high-intensity focussed ultrasound

No. of studies/patients	Study design	Methodological quality	Consistency of results	Directness of evidence	Magnitude of effect, %	Other modifying factors¹	Level of evidence
Outcome: biochemical disease-free survival rate
2/367	Observational, case series	Serious limitations² (−1)	No important inconsistency	Direct	66–77 at 5 yr, 69 at 7 yr	Publication bias likely	Very low

Outcome: negative biopsy rate
10/1849	Observational, case series	Serious limitations² (−1)	Important inconsistency	Direct	86 at 3 mo, 65–94 (point in time not specified)	Publication bias likely; lack of precise data	Very low

Outcome: overall survival rate
1/140	Observational, case series	Serious limitations² (−1)	Only one trial	Direct	90 at 5 yr, 83 at 8 yr	Publication bias likely	Very low

Outcome: prostate-cancer specific survival rate
1/140	Observational, case series	Serious limitations² (−1)	Only one trial	Direct	100 at 5 yr, 98 at 8 yr	Publication bias likely	Very low

Outcome: adverse events urinary tract³
4/702–11/1907⁴	Observational, case series	Serious limitations² (−1)	Important inconsistency	Direct	2–58	Publication bias likely	Very low

Outcome: adverse events potency⁵
8/1714	Observational, case series	Serious limitations² (−1)	Important inconsistency	Direct	18–0	Publication bias likely	Very low

Outcome: adverse events rectum⁶
1/184–6/969⁷	Observational, case series	Serious limitations² (−1)	Important inconsistency	Direct	0–15	Publication bias likely	Very low

Outcome: pain
6/927	Observational, case series	Serious limitations² (−1)	No important inconsistency	Direct	1–6	Publication bias likely	Very low

Outcome: IEFF (30-point scale)
No evidence

Outcome: IPSS (35-point scale)
4/671	Observational, case series	Serious limitations² (−1)	Important inconsistency	Direct	Improved by 1–4 points, or worsened by 3 points (baseline vs last follow-up)	Publication bias likely	Very low

Outcome: IPSS-Quality of Life (6-point scale)
3/525	Observational, case series	Serious limitations² (−1)	No important inconsistency	Direct	Changed by ±1 point (baseline vs last follow-up)	Publication bias likely	Very low

IEFF = International Index of Erectile Function; IPSS = International Prostate Symptom Score.

¹ Low incidence, lack of precise data, strong or very strong association, high risk of publication bias, dose-efficacy gradient, residual confounding plausible.

² All observational studies have been downgraded from low quality to very low quality because of case series with lack of control group; further factors lowering the quality of evidence apply, such as the likely occurrence of publication bias.

³ Adverse events urinary tract: bladder neck/urethral stricture/stenosis, prolonged urinary retention, urinary tract infection, urinary incontinence.

⁴ Not all adverse events concerning urinary tract were assessed in all studies.

⁵ Adverse events potency: impotence/erectile dysfunction.

⁶ Adverse events rectum: rectal burn, rectourethral fistula.

⁷ Not all adverse events concerning rectum were assessed in all studies.

References in context

Table 4 shows the evidence profile of Ablatherm HIFU as a primary therapy option in prostate cancer.
Go to context

The evidence concerning the patient-relevant outcomes, overall survival, and prostate cancer-specific survival is scarce because these factors were only assessed in one case series [18] x A. Blana, F.J. Murat, B. Walter, et al. First analysis of the long-term results with transrectal HIFU in patients with localised prostate cancer. Eur Urol. 2008;53:1194-1203 Abstract, Full-text, PDF, Crossref. . Adverse events of the urinary tract included bladder neck/urethral stenosis/stricture (2–17%), prolonged urinary retention (3–14%), urinary tract infection (2–58%), and urinary incontinence (2–34%). Adverse events of the rectum included rectal burn (0–15%) as well as rectourethral fistula (0–3%). In six case series, outcomes in terms of quality of life were assessed using self-administered questionnaires that yielded either little differences from pre- to post-HIFU treatment or controversial results 19 x A. Blana, B. Walter, S. Rogenhofer, W.F. Wieland. High-intensity focused ultrasound for the treatment of localized prostate cancer: 5-year experience. Urology. 2004;63:297-300 Crossref. , 20 x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. Results and side effects of high-intensity focused ultrasound in localized prostate cancer. J Endourol. 2001;15:437-440 discussion 447–8 Crossref. , 21 x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. The status of high-intensity focused ultrasound in the treatment of localized prostate cancer and the impact of a combined resection. Curr Urol Rep. 2003;4:248-252 Crossref. , 23 x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high intensity focused ultrasound for the treatment of localized prostate cancer: factors influencing the outcome. Eur Urol. 2001;40:124-129 Crossref. , 27 x L. Poissonnier, J.-Y. Chapelon, O. Rouvière, et al. Control of prostate cancer by transrectal HIFU in 227 patients. Eur Urol. 2007;51:381-387 Abstract, Full-text, PDF, Crossref. , and 33 x B. Walter, S. Rogenhofer, W.F. Wieland, A. Blana. Combination from TUR-P and high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer—experience with 70 patients. J Urologie Urogynakologie. 2004;11:5-10 .

3.1.2. Salvage therapy

Ablatherm HIFU as a salvage therapy option in recurrent prostate cancer after EBRT failure was assessed in three case series, all of which were published from one study centre in France 34 x M. Colombel, L. Poissonnier, X. Martin, A. Gelet. Clinical results of the prostate HIFU project. Eur Urol Suppl. 2006;5:491-494 Abstract, Full-text, PDF, Crossref. , 35 x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high-intensity focused ultrasound: minimally invasive therapy of localized prostate cancer [published correction appears in J Endourol 2000;14:697]. J Endourol. 2000;14:519-528 Crossref. , and 36 x A. Gelet, J.Y. Chapelon, L. Poissonnier, et al. Local recurrence of prostate cancer after external beam radiotherapy: early experience of salvage therapy using high-intensity focused ultrasonography. Urology. 2004;63:625-629 Crossref. . Study characteristics are shown in Table 5. Between 71 and 82 patients were treated with HIFU following recurrence of prostate cancer after EBRT. In one case series patients were recruited consecutively [35] x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high-intensity focused ultrasound: minimally invasive therapy of localized prostate cancer [published correction appears in J Endourol 2000;14:697]. J Endourol. 2000;14:519-528 Crossref. . Mean patient age was 67–71 yr; mean preoperative PSA level was 8 ng/ml, Gleason score was ≤8 in most patients, and preoperative prostate volume was between 21 and 35 ml. Neoadjuvant ADT was administered to between 9% and 30% of the men. Patients were treated with HIFU one (41%) to five (1%) times and were followed up for a mean of 15–18 mo.

Table 5 Ablatherm high-intensity focussed ultrasound: salvage therapy

Study	Colombel et al [34] x M. Colombel, L. Poissonnier, X. Martin, A. Gelet. Clinical results of the prostate HIFU project. Eur Urol Suppl. 2006;5:491-494 Abstract, Full-text, PDF, Crossref.	Gelet et al [36] x A. Gelet, J.Y. Chapelon, L. Poissonnier, et al. Local recurrence of prostate cancer after external beam radiotherapy: early experience of salvage therapy using high-intensity focused ultrasonography. Urology. 2004;63:625-629 Crossref.	Gelet et al [35] x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high-intensity focused ultrasound: minimally invasive therapy of localized prostate cancer [published correction appears in J Endourol 2000;14:697]. J Endourol. 2000;14:519-528 Crossref.
Country	FR	FR	FR
Patients, No.	71	71	82
Patients, age, yr	NA	Ø 67 ± 6	Ø 71 ± 6
Tumour stage	Local recurrence	Local recurrence (T1–T3)	T1–T2
Primary treatment	EBRT	EBRT	EBRT
Neoadjuvant ADT, % of pts	NA	30	9
TURP prior to/combined with HIFU, % of pts	NA	NA	NA
Follow-up, mo (range)	Ø 15	Ø 15 (6–86)	Ø 18

ADT = androgen-deprivation therapy; EBRT = external-beam radiation therapy; FR = France; HIFU = high-intensity focussed ultrasound; NA = not available; Ø = mean plus or minus standard deviation; pts = patients; TURP = transurethral resection of the prostate.

References in context

Study characteristics are shown in Table 5.
Go to context

Table 6 shows the evidence profile of Ablatherm HIFU in the salvage setting in prostate cancer. The negative biopsy rate was 80% at 15 mo in one trial [34] x M. Colombel, L. Poissonnier, X. Martin, A. Gelet. Clinical results of the prostate HIFU project. Eur Urol Suppl. 2006;5:491-494 Abstract, Full-text, PDF, Crossref. and between 78% and 80% in the remaining studies; the point in time of biopsy was not shown 35 x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high-intensity focused ultrasound: minimally invasive therapy of localized prostate cancer [published correction appears in J Endourol 2000;14:697]. J Endourol. 2000;14:519-528 Crossref. , and 36 x A. Gelet, J.Y. Chapelon, L. Poissonnier, et al. Local recurrence of prostate cancer after external beam radiotherapy: early experience of salvage therapy using high-intensity focused ultrasonography. Urology. 2004;63:625-629 Crossref. . Evidence concerning patient-relevant outcomes is limited to adverse events concerning the urinary tract, such as bladder neck/urethral stricture/stenosis (17%), prolonged urinary retention (6%), urinary tract infection (1–6%), urinary incontinence (7–35%), as well as potency, the rectum, and pain. One case series assessed the quality of life by self-administered questionnaires, but data were not presented [35] x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high-intensity focused ultrasound: minimally invasive therapy of localized prostate cancer [published correction appears in J Endourol 2000;14:697]. J Endourol. 2000;14:519-528 Crossref. .

Table 6 Evidence profile: salvage high-intensity focussed ultrasound

No. of studies/patients	Study design	Methodological quality	Consistency of results	Directness of evidence	Magnitude of effect, %	Other modifying factors¹	Level of evidence
Outcome: biochemical disease-free survival rate
No evidence

Outcome: negative biopsy rate
3/224	Observational, case series	Serious limitations² (−1)	Important inconsistency	Direct	80 at 15 mo, 78–80 (point in time not specified)	Publication bias likely; lack of precise data	Very low
Outcome: overall survival rate
No evidence

Outcome: prostate-cancer specific survival rate
No evidence

Outcome: adverse events urinary tract³
1/82–3/224⁴	Observational, case series	Serious limitations² (−1)	Important inconsistency	Direct	1–35	Publication bias likely	Very low
Outcome: adverse events potency⁵
1/82	Observational, case series	Serious limitations² (−1)	Only one trial	Direct	77	Publication bias likely	Very low
Outcome: adverse events rectum⁶
3/224	Observational, case series	Serious limitations² (−1)	No important inconsistency	Direct	1–6	Publication bias likely	Very low
Outcome: pain
1/82	Observational, case series	Serious limitations² (−1)	Only one trial	Direct	1	Publication bias likely	Very low
Outcome: IEFF (30-point scale)
No evidence

Outcome: IPSS (35-point scale)
No evidence

Outcome: IPSS-Quality of Life (6-point scale)
No evidence

IEFF = International Index of Erectile Function; IPSS = International Prostate Symptom Score.

¹ Low incidence, lack of precise data, strong or very strong association, high risk of publication bias, dose-efficacy gradient, residual confounding plausible.

³ Adverse events urinary tract: bladder neck/urethral stricture/stenosis, prolonged urinary retention, urinary tract infection, urinary incontinence.

⁴ Not all adverse events concerning urinary tract were assessed in all studies.

⁵ Adverse events potency: impotence/erectile dysfunction.

⁶ Adverse events rectum: rectourethral fistula.

References in context

Table 6 shows the evidence profile of Ablatherm HIFU in the salvage setting in prostate cancer.
Go to context

We were not able to identify any evidence concerning the use of Ablatherm HIFU in recurrent prostate cancer following RP.

3.2. Sonablate high-intensity focussed ultrasound

3.2.1. Primary therapy

We retrieved seven case series assessing Sonablate HIFU as a primary therapy option in prostate cancer that were carried out by three study groups in the United Kingdom, Italy, and Japan 17 x Ahmed HU, Zacharakis E, Dudderidge T, et al. High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series. Br J Cancer 2009 7;101:19–26. , 25 x L. Mearini, L. D’Urso, D. Collura, et al. Visually directed transrectal high intensity focused ultrasound for the treatment of prostate cancer: a preliminary report on the Italian experience. J Urol. 2009;181:105-111 discussion 111–2 , 26 x S. Muto, T. Yoshii, K. Saito, et al. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn J Clin Oncol. 2008;38:192-199 Crossref. , 29 x T. Uchida, S. Baba, A. Irie, et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study. Hinyokika Kiyo. 2005;51:651-658 , 30 x T. Uchida, H. Ohkusa, Y. Nagata, et al. Treatment of localized prostate cancer using high-intensity focused ultrasound. BJU Int. 2006;97:56-61 Crossref. , 31 x T. Uchida, H. Ohkusa, H. Yamashita, et al. Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer. Int J Urol. 2006;13:228-233 Crossref. , and 32 x T. Uchida, S. Shoji, M. Nakano, et al. Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: eight-year experience. Int J Urol. 2009;16:881-886 Crossref. . As shown in Table 7, between 63 and 517 patients were treated with Sonablate HIFU who were recruited consecutively in four case series 25 x L. Mearini, L. D’Urso, D. Collura, et al. Visually directed transrectal high intensity focused ultrasound for the treatment of prostate cancer: a preliminary report on the Italian experience. J Urol. 2009;181:105-111 discussion 111–2 , 29 x T. Uchida, S. Baba, A. Irie, et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study. Hinyokika Kiyo. 2005;51:651-658 , 30 x T. Uchida, H. Ohkusa, Y. Nagata, et al. Treatment of localized prostate cancer using high-intensity focused ultrasound. BJU Int. 2006;97:56-61 Crossref. , and 32 x T. Uchida, S. Shoji, M. Nakano, et al. Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: eight-year experience. Int J Urol. 2009;16:881-886 Crossref. . Both localised (T1–T2, N0, M0) as well as locally advanced (T3, N0, M0) prostate cancers were treated using the Sonablate device. Median patient age, reported in all but one study, was between 68 and 72 yr 25 x L. Mearini, L. D’Urso, D. Collura, et al. Visually directed transrectal high intensity focused ultrasound for the treatment of prostate cancer: a preliminary report on the Italian experience. J Urol. 2009;181:105-111 discussion 111–2 , 26 x S. Muto, T. Yoshii, K. Saito, et al. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn J Clin Oncol. 2008;38:192-199 Crossref. , 29 x T. Uchida, S. Baba, A. Irie, et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study. Hinyokika Kiyo. 2005;51:651-658 , 30 x T. Uchida, H. Ohkusa, Y. Nagata, et al. Treatment of localized prostate cancer using high-intensity focused ultrasound. BJU Int. 2006;97:56-61 Crossref. , 31 x T. Uchida, H. Ohkusa, H. Yamashita, et al. Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer. Int J Urol. 2006;13:228-233 Crossref. , and 32 x T. Uchida, S. Shoji, M. Nakano, et al. Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: eight-year experience. Int J Urol. 2009;16:881-886 Crossref. . The remaining study reported a mean age of 64 yr [17] x Ahmed HU, Zacharakis E, Dudderidge T, et al. High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series. Br J Cancer 2009 7;101:19–26. . Median PSA level was 5–10 ng/ml in six studies 25 x L. Mearini, L. D’Urso, D. Collura, et al. Visually directed transrectal high intensity focused ultrasound for the treatment of prostate cancer: a preliminary report on the Italian experience. J Urol. 2009;181:105-111 discussion 111–2 , 26 x S. Muto, T. Yoshii, K. Saito, et al. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn J Clin Oncol. 2008;38:192-199 Crossref. , 29 x T. Uchida, S. Baba, A. Irie, et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study. Hinyokika Kiyo. 2005;51:651-658 , 30 x T. Uchida, H. Ohkusa, Y. Nagata, et al. Treatment of localized prostate cancer using high-intensity focused ultrasound. BJU Int. 2006;97:56-61 Crossref. , 31 x T. Uchida, H. Ohkusa, H. Yamashita, et al. Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer. Int J Urol. 2006;13:228-233 Crossref. , and 32 x T. Uchida, S. Shoji, M. Nakano, et al. Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: eight-year experience. Int J Urol. 2009;16:881-886 Crossref. ; mean PSA was given in one study and was 8 ng/ml [17] x Ahmed HU, Zacharakis E, Dudderidge T, et al. High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series. Br J Cancer 2009 7;101:19–26. . Gleason score was ≤7 in most patients, and median preoperative prostate volume was 22–33 ml. Between 29% and 66% of men received neoadjuvant ADT. TURP was either not carried out or no information was provided. Patients received one to four HIFU treatments, but most (79–86%) were treated once. Median follow-up was between 14 and 34 mo 25 x L. Mearini, L. D’Urso, D. Collura, et al. Visually directed transrectal high intensity focused ultrasound for the treatment of prostate cancer: a preliminary report on the Italian experience. J Urol. 2009;181:105-111 discussion 111–2 , 26 x S. Muto, T. Yoshii, K. Saito, et al. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn J Clin Oncol. 2008;38:192-199 Crossref. , 29 x T. Uchida, S. Baba, A. Irie, et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study. Hinyokika Kiyo. 2005;51:651-658 , 30 x T. Uchida, H. Ohkusa, Y. Nagata, et al. Treatment of localized prostate cancer using high-intensity focused ultrasound. BJU Int. 2006;97:56-61 Crossref. , 31 x T. Uchida, H. Ohkusa, H. Yamashita, et al. Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer. Int J Urol. 2006;13:228-233 Crossref. , and 32 x T. Uchida, S. Shoji, M. Nakano, et al. Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: eight-year experience. Int J Urol. 2009;16:881-886 Crossref. ; mean follow-up was 12 mo as reported in one study [17] x Ahmed HU, Zacharakis E, Dudderidge T, et al. High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series. Br J Cancer 2009 7;101:19–26. .

Table 7 Sonablate high-intensity focussed ultrasound: primary therapy

Study	Ahmed et al [17] x Ahmed HU, Zacharakis E, Dudderidge T, et al. High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series. Br J Cancer 2009 7;101:19–26.	Mearini et al [25] x L. Mearini, L. D’Urso, D. Collura, et al. Visually directed transrectal high intensity focused ultrasound for the treatment of prostate cancer: a preliminary report on the Italian experience. J Urol. 2009;181:105-111 discussion 111–2	Uchida et al [32] x T. Uchida, S. Shoji, M. Nakano, et al. Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: eight-year experience. Int J Urol. 2009;16:881-886 Crossref.	Muto et al [26] x S. Muto, T. Yoshii, K. Saito, et al. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn J Clin Oncol. 2008;38:192-199 Crossref.	Uchida et al [31] x T. Uchida, H. Ohkusa, H. Yamashita, et al. Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer. Int J Urol. 2006;13:228-233 Crossref.	Uchida et al [30] x T. Uchida, H. Ohkusa, Y. Nagata, et al. Treatment of localized prostate cancer using high-intensity focused ultrasound. BJU Int. 2006;97:56-61 Crossref.	Uchida et al [29] x T. Uchida, S. Baba, A. Irie, et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study. Hinyokika Kiyo. 2005;51:651-658
Country	GB: 2 centres	IT: 2 centres	JP	JP	JP	JP	JP: multicentre
Patients, No.	172	163	517	70 (A: full ablation 41; B: focal ablation 29)	181	63	72
Patients, age	Ø 64 ± 8 (47–88)	M (IQR): 72 (68–75)	M: 68 (45–88)	M: 72 (61–80)	M: 70 (45–88)	M: 71 (45–87)	M: 72 (45–79)
Tumour stage	≤T1c–T3bN0M0	T1c–T3aN0M0	T1c–T3N0M0	T1c–T2N0M0	T1c–T2bN0M0	T1c–T2bN0M0	T1c–T2bN0M0
Neoadjuvant ADT, % of pts	29	0	66	34	52	0	0
TURP prior to/combined with HIFU, % of pts	0	0	NA	NA	NA	0	NA
Follow-up, mo. (range)	Ø 12 ± 8 (5–25)	M: 24 (12–41)	M: 24 (2–88)	M: 34 (8–45)	M: 18 (4–68)	M: 22 (3–63)	M: 14 (2–24)

ADT = androgen-deprivation therapy; GB = United Kingdom; HIFU = high-intensity focussed ultrasound; IQR = interquartile range; IT = Italy; JP = Japan; M = median; NA = not available; pts = patients; Ø = mean plus or minus standard deviation; TURP = transurethral resection of the prostate.

References in context

As shown in Table 7, between 63 and 517 patients were treated with Sonablate HIFU who were recruited consecutively in four case series [25,29,30,32].
Go to context

The evidence profile of Sonablate HIFU as a primary treatment option for prostate cancer is shown in Table 8. The biochemical disease-free survival rate was given in six case series and varied between 78% and 84% at 1 yr, 0–91% at 2 yr, 20–86% at 3 yr, and 45–84% at 5 yr 25 x L. Mearini, L. D’Urso, D. Collura, et al. Visually directed transrectal high intensity focused ultrasound for the treatment of prostate cancer: a preliminary report on the Italian experience. J Urol. 2009;181:105-111 discussion 111–2 , 26 x S. Muto, T. Yoshii, K. Saito, et al. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn J Clin Oncol. 2008;38:192-199 Crossref. , 29 x T. Uchida, S. Baba, A. Irie, et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study. Hinyokika Kiyo. 2005;51:651-658 , 30 x T. Uchida, H. Ohkusa, Y. Nagata, et al. Treatment of localized prostate cancer using high-intensity focused ultrasound. BJU Int. 2006;97:56-61 Crossref. , 31 x T. Uchida, H. Ohkusa, H. Yamashita, et al. Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer. Int J Urol. 2006;13:228-233 Crossref. , and 32 x T. Uchida, S. Shoji, M. Nakano, et al. Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: eight-year experience. Int J Urol. 2009;16:881-886 Crossref. . The negative biopsy rate was assessed in five studies 25 x L. Mearini, L. D’Urso, D. Collura, et al. Visually directed transrectal high intensity focused ultrasound for the treatment of prostate cancer: a preliminary report on the Italian experience. J Urol. 2009;181:105-111 discussion 111–2 , 26 x S. Muto, T. Yoshii, K. Saito, et al. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn J Clin Oncol. 2008;38:192-199 Crossref. , 29 x T. Uchida, S. Baba, A. Irie, et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study. Hinyokika Kiyo. 2005;51:651-658 , 30 x T. Uchida, H. Ohkusa, Y. Nagata, et al. Treatment of localized prostate cancer using high-intensity focused ultrasound. BJU Int. 2006;97:56-61 Crossref. , and 32 x T. Uchida, S. Shoji, M. Nakano, et al. Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: eight-year experience. Int J Urol. 2009;16:881-886 Crossref. , but the point in time of biopsy was only presented in three of them 25 x L. Mearini, L. D’Urso, D. Collura, et al. Visually directed transrectal high intensity focused ultrasound for the treatment of prostate cancer: a preliminary report on the Italian experience. J Urol. 2009;181:105-111 discussion 111–2 , 26 x S. Muto, T. Yoshii, K. Saito, et al. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn J Clin Oncol. 2008;38:192-199 Crossref. , and 29 x T. Uchida, S. Baba, A. Irie, et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study. Hinyokika Kiyo. 2005;51:651-658 . The negative biopsy rate was 19–89% at 6 mo and 77–84% at 12 mo 25 x L. Mearini, L. D’Urso, D. Collura, et al. Visually directed transrectal high intensity focused ultrasound for the treatment of prostate cancer: a preliminary report on the Italian experience. J Urol. 2009;181:105-111 discussion 111–2 , 26 x S. Muto, T. Yoshii, K. Saito, et al. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn J Clin Oncol. 2008;38:192-199 Crossref. , and 29 x T. Uchida, S. Baba, A. Irie, et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study. Hinyokika Kiyo. 2005;51:651-658 . There is lack of evidence concerning overall survival and prostate cancer–specific survival. Adverse events reported included urinary tract with bladder neck/urethral stricture/stenosis (4–30%), prolonged urinary retention (1–13%), urinary tract infection (4–24%), and urinary incontinence (1–2%). Impotence/erectile dysfunction and retrograde ejaculation occurred in 20–39% and 1–20% of men, respectively. All case series assessed quality of life by self-administered questionnaires. Results were only presented in four of the seven trials, however 17 x Ahmed HU, Zacharakis E, Dudderidge T, et al. High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series. Br J Cancer 2009 7;101:19–26. , 25 x L. Mearini, L. D’Urso, D. Collura, et al. Visually directed transrectal high intensity focused ultrasound for the treatment of prostate cancer: a preliminary report on the Italian experience. J Urol. 2009;181:105-111 discussion 111–2 , 26 x S. Muto, T. Yoshii, K. Saito, et al. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn J Clin Oncol. 2008;38:192-199 Crossref. , and 29 x T. Uchida, S. Baba, A. Irie, et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study. Hinyokika Kiyo. 2005;51:651-658 .

Table 8 Evidence profile of Sonablate high-intensity focussed ultrasound

No. of studies/patients	Study design	Methodological quality	Consistency of results	Directness of evidence	Magnitude of effect, %	Other modifying factors¹	Level of evidence
Outcome: biochemical disease-free survival rate
6/1066	Observational, case series	Serious limitations² (−1)	Important inconsistency		78–84 at 1 yr, 0–91 at 2 yr, 20– 6 at 3 yr, 45– 4 at 5 yr	Publication bias likely	Very low
Outcome: negative biopsy rate
5/885	Observational, case series	Serious limitations² (−1)	Important inconsistency		19–89 at 6 mo, 77–84 at 12 mo	Publication bias likely	Very low
Outcome: overall survival rate
No evidence

Outcome: prostate-cancer specific survival rate
No evidence

Outcome: adverse events urinary tract³
2/242–7/1238⁴	Observational, case series	Serious limitations² (−1)	Important inconsistency	Direct	1–30	Publication bias likely	Very low
Outcome: adverse events potency⁵
4/833–5/1005⁶	Observational, case series	Serious limitations² (−1)	Important inconsistency	Direct	1–39	Publication bias likely	Very low
Outcome: adverse events rectum⁷
1/72–5/1096⁸	Observational, case series	Serious limitations² (−1)	No important inconsistency	Direct	0–2	Publication bias likely	Very low
Outcome: pain
No evidence

Outcome: IEFF (30-point scale)
1/172	Observational, case series	Serious limitations² (−1)	Only one trial	Direct	Worsened by 6 points (baseline vs 12 mo post HIFU)	No	Very low
Outcome: IPSS (35-point scale)
4/671	Observational, case series	Serious limitations² (−1)	No important inconsistency	Direct	Changed by ± 1 point (baseline vs 12 mo post HIFU)	Publication bias likely	Very low
Outcome: IPSS-Quality of Life (6-point scale)
No evidence

HIFU = high-intensity focussed ultrasound; IEFF = International Index of Erectile Function; IPSS = International Prostate Symptom Score.

¹ Low incidence, lack of precise data, strong or very strong association, high risk of publication bias, dose-efficacy gradient, residual confounding plausible.

³ Adverse events urinary tract: bladder neck/ urethral stricture/ stenosis, prolonged urinary retention, urinary tract infection, urinary incontinence.

⁴ Not all adverse events concerning urinary tract were assessed in all studies.

⁵ Adverse events potency: impotence/ erectile dysfunction, retrograde ejaculation.

⁶ Not all adverse events concerning potency were assessed in all studies.

⁷ Adverse events rectum: rectal burn, rectourethral fistula, stool incontinence.

⁸ Not all adverse events concerning rectum were assessed in all studies.

References in context

The evidence profile of Sonablate HIFU as a primary treatment option for prostate cancer is shown in Table 8.
Go to context

3.2.2. Salvage therapy

We were not able to identify any evidence concerning the use of Sonablate HIFU as a salvage therapy option in recurrent prostate cancer.

3.3. Discussion

Although HIFU has been used for the treatment of prostate cancer since the 1990s, good-quality evidence concerning its efficacy and safety is still lacking. The available evidence identified in our literature search has some limitations. First, up-to-date evidence solely stems from uncontrolled case series. Prospective (randomised) controlled trials comparing HIFU with established surgical (RP) and nonsurgical (radiotherapy) treatment options or with no treatment (active surveillance) have not been published. Unlike the framework applied to the investigation of new drugs, at present the development and assessment of surgical innovations takes place in an unstructured and unregulated manner [37] x J.S. Barkun, J.K. Aronson, L.S. Feldman, G.J. Maddern, S.M. Strasberg, for the Balliol Collaboration. Evaluation and stages of surgical innovations. Lancet. 2009;374:1089-1096 Crossref. . Taking into consideration the challenges associated with the evaluation of surgical procedures [38] x P.L. Ergina, J.A. Cook, J.M. Blazeby, et al. Challenges in evaluating surgical innovation. Lancet. 2009;374:1097-1104 Crossref. , the IDEAL recommendations have recently been proposed to structure the investigation of surgical innovations [39] x P. McCulloch, D.G. Altman, W.B. Campbell, et al. No surgical innovation without evaluation: the IDEAL recommendations. Lancet. 2009;374:1105-1112 Crossref. . The IDEAL model suggests five interconnected stages related to the development and assessment of surgical innovations, namely innovation, development, exploration, assessment, and long-term study. In addition, the authors present various study designs to overcome obstacles associated with the feasibility of randomised trials as well as potential improvements for reporting [39] x P. McCulloch, D.G. Altman, W.B. Campbell, et al. No surgical innovation without evaluation: the IDEAL recommendations. Lancet. 2009;374:1105-1112 Crossref. . Second, because the 20 case series we identified were only published by seven international study groups, publication bias is very likely. Hence no definite conclusion can be drawn about the overall patient population treated with HIFU so far. Third, in seven case series, patients were treated with various models of either the Ablatherm or Sonablate device within one trial, making a comparison of outcomes difficult even across one study population. Fourth, patients were recruited consecutively in only nine case series, which could introduce selection bias. Further bias could have been introduced by including heterogeneous patient populations with variations in prognostic factors and neoadjuvant treatments, such as hormonal therapy or TURP. Fifth, the number of HIFU treatments varied between one and five. Recurrent HIFU treatment, however, has not been judged as a HIFU failure. Data on long-term follow-up after HIFU treatment are sparse, and the quality of available data is insufficient. In the case series identified, the efficacy of HIFU was mainly assessed using surrogate outcomes, such as biochemical disease-free survival rate and negative biopsy result. It remains questionable whether surrogate outcomes correlate with patient-relevant outcomes such as overall survival, prostate-cancer specific survival, and quality of life. In addition, in the studies identified, biochemical treatment failure was either not defined 17 x Ahmed HU, Zacharakis E, Dudderidge T, et al. High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series. Br J Cancer 2009 7;101:19–26. , 19 x A. Blana, B. Walter, S. Rogenhofer, W.F. Wieland. High-intensity focused ultrasound for the treatment of localized prostate cancer: 5-year experience. Urology. 2004;63:297-300 Crossref. , 20 x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. Results and side effects of high-intensity focused ultrasound in localized prostate cancer. J Endourol. 2001;15:437-440 discussion 447–8 Crossref. , 22 x C.G. Chaussy, S. Thüroff, C.G. Chaussy, S. Thüroff. High-intensive focused ultrasound in localized prostate cancer. J Endourol. 2000;14:293-299 Crossref. , 28 x S. Thüroff, C. Chaussy, G. Vallancien, et al. High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study. J Endourol. 2003;17:673-677 , 33 x B. Walter, S. Rogenhofer, W.F. Wieland, A. Blana. Combination from TUR-P and high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer—experience with 70 patients. J Urologie Urogynakologie. 2004;11:5-10 , and 34 x M. Colombel, L. Poissonnier, X. Martin, A. Gelet. Clinical results of the prostate HIFU project. Eur Urol Suppl. 2006;5:491-494 Abstract, Full-text, PDF, Crossref. or defined according to the Phoenix criteria 18 x A. Blana, F.J. Murat, B. Walter, et al. First analysis of the long-term results with transrectal HIFU in patients with localised prostate cancer. Eur Urol. 2008;53:1194-1203 Abstract, Full-text, PDF, Crossref. , 25 x L. Mearini, L. D’Urso, D. Collura, et al. Visually directed transrectal high intensity focused ultrasound for the treatment of prostate cancer: a preliminary report on the Italian experience. J Urol. 2009;181:105-111 discussion 111–2 , and 32 x T. Uchida, S. Shoji, M. Nakano, et al. Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: eight-year experience. Int J Urol. 2009;16:881-886 Crossref. , the American Society for Therapeutic Radiology and Oncology (ASTRO) criteria 21 x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. The status of high-intensity focused ultrasound in the treatment of localized prostate cancer and the impact of a combined resection. Curr Urol Rep. 2003;4:248-252 Crossref. , 24 x H.M. Lee, J.H. Hong, H.Y. Choi, H.M. Lee, J.H. Hong, H.Y. Choi. High-intensity focused ultrasound therapy for clinically localized prostate cancer. Prostate Cancer Prostatic Dis. 2006;9:439-443 Crossref. , 26 x S. Muto, T. Yoshii, K. Saito, et al. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn J Clin Oncol. 2008;38:192-199 Crossref. , 29 x T. Uchida, S. Baba, A. Irie, et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study. Hinyokika Kiyo. 2005;51:651-658 , 30 x T. Uchida, H. Ohkusa, Y. Nagata, et al. Treatment of localized prostate cancer using high-intensity focused ultrasound. BJU Int. 2006;97:56-61 Crossref. , 31 x T. Uchida, H. Ohkusa, H. Yamashita, et al. Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer. Int J Urol. 2006;13:228-233 Crossref. , and 36 x A. Gelet, J.Y. Chapelon, L. Poissonnier, et al. Local recurrence of prostate cancer after external beam radiotherapy: early experience of salvage therapy using high-intensity focused ultrasonography. Urology. 2004;63:625-629 Crossref. , or predefined criteria 23 x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high intensity focused ultrasound for the treatment of localized prostate cancer: factors influencing the outcome. Eur Urol. 2001;40:124-129 Crossref. , 27 x L. Poissonnier, J.-Y. Chapelon, O. Rouvière, et al. Control of prostate cancer by transrectal HIFU in 227 patients. Eur Urol. 2007;51:381-387 Abstract, Full-text, PDF, Crossref. , 34 x M. Colombel, L. Poissonnier, X. Martin, A. Gelet. Clinical results of the prostate HIFU project. Eur Urol Suppl. 2006;5:491-494 Abstract, Full-text, PDF, Crossref. , and 35 x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high-intensity focused ultrasound: minimally invasive therapy of localized prostate cancer [published correction appears in J Endourol 2000;14:697]. J Endourol. 2000;14:519-528 Crossref. . Both the Phoenix criteria and the ASTRO criteria have been validated in PSA failure after radiotherapy only. Recently, a new definition, the so-called Stuttgart definition—a PSA increase of 1.2 ng/ml above the PSA nadir value—has been suggested to judge PSA failure following HIFU treatment [40] x A. Blana, S.C. Brown, C. Chaussy, et al. High-intensity focused ultrasound for prostate cancer: comparative definitions of biochemical failure. BJU Int. 2009;104:1058-1062 Crossref. . However, this definition remains to be validated in prospective trials.

A direct comparison of patient-relevant outcomes between patients undergoing conventional treatment for prostate cancer, such as RP, radiotherapy, or active surveillance, and those undergoing HIFU is not achievable due to lack of comparative studies. Although studies comparing the various treatment options for prostate cancer would be of great value, only one randomised controlled trial comparing RP and watchful waiting has been published so far. It showed that RP is superior to watchful waiting in terms of overall survival, disease-specific survival, and the risk of local and systemic disease progression [4] x A. Bill-Axelson, L. Holmberg, M. Ruutu, M. Haggman, S.O. Andersson, S. Bratell. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2005;352:1977-1984 Crossref. . However, the available literature indicates that most of the limitations reported for HIFU treatment here also apply for RP, including the radical retropubic prostatectomy (RRP), laparoscopic radical prostatectomy (LRP), and robot-assisted laparoscopic radical prostatectomy (RARP) approach 41 x V. Ficarra, G. Novara, W. Artibani, et al. Retropubic, laparoscopic, and robot-assisted radical prostatectomy: a systematic review and cumulative analysis of comparative studies. Eur Urol. 2009;55:1037-1063 Abstract, Full-text, PDF, Crossref. , 42 x D.G. Murphy, A. Bjartell, V. Ficarra, et al. Downsides of robot-assisted laparoscopic radical prostatectomy: limitations and complications. Eur Urol. 2010;57:735-746 Abstract, Full-text, PDF, Crossref. , and 43 x V. Ficarra, S. Cavalleri, G. Novara, M. Aragona, W. Artibani. Evidence from robot-assisted laparoscopic radical prostatectomy: a systematic review. Eur Urol. 2007;51:45-56 Abstract, Full-text, PDF, Crossref. . Adverse events associated with RRP, LRP, and RARP are similar to those observed in HIFU treatment. Using a standardised reporting methodology, the overall rate of medical and surgical complications in patients undergoing RRP or LRP has been reported to be 10% and 20%, respectively [44] x F. Rabbani, L.H. Yunis, R. Pinochet, et al. Comprehensive standardized report of complications of retropubic and laparoscopic radical prostatectomy. Eur Urol. 2010;57:371-386 Abstract, Full-text, PDF, Crossref. . However, LRP was associated with a lower incidence of major surgical complications compared with RRP [44] x F. Rabbani, L.H. Yunis, R. Pinochet, et al. Comprehensive standardized report of complications of retropubic and laparoscopic radical prostatectomy. Eur Urol. 2010;57:371-386 Abstract, Full-text, PDF, Crossref. . Furthermore, when applying standardised criteria, early complications were observed in 22% of patients undergoing RARP for clinically localised prostate cancer [45] x G. Novara, V. Ficarra, C. D’Elia, S. Secco, S. Cavalleri, W. Artibani. Prospective evaluation with standardised criteria for postoperative complications after robotic-assisted laparoscopic radical prostatectomy. Eur Urol. 2010;57:363-370 Abstract, Full-text, PDF, Crossref. . Although most patients experienced minor adverse events, about 3% suffered from severe adverse events [45] x G. Novara, V. Ficarra, C. D’Elia, S. Secco, S. Cavalleri, W. Artibani. Prospective evaluation with standardised criteria for postoperative complications after robotic-assisted laparoscopic radical prostatectomy. Eur Urol. 2010;57:363-370 Abstract, Full-text, PDF, Crossref. . It has been shown that the overall complication rate decreases as the surgeon's experience increases 45 x G. Novara, V. Ficarra, C. D’Elia, S. Secco, S. Cavalleri, W. Artibani. Prospective evaluation with standardised criteria for postoperative complications after robotic-assisted laparoscopic radical prostatectomy. Eur Urol. 2010;57:363-370 Abstract, Full-text, PDF, Crossref. , and 46 x R.F. Coelho, K.J. Palmer, B. Rocco, et al. Early complication rates in a single-surgeon series of 2500 robotic-assisted radical prostatectomies: report applying a standardized grading system. Eur Urol. 2010;57:945-952 Abstract, Full-text, PDF, Crossref. .

In terms of complication rates associated with radiotherapy, about 16% of patients experience significant genitourinary toxicity including cystitis (5%), haematuria (5%), urinary stricture (7%), and urinary incontinence (5%). In addition, approximately 10% of patients suffer significant gastrointestinal toxicity, most often proctitis (8%), followed by chronic diarrhoea (4%) and small bowel obstruction (1%). Leg oedema occurs in about 2% of patients [2] x Heidenreich A, Bolla M, Joniau S, et al. Guidelines on prostate cancer. European Association of Urology Web site. http://www.uroweb.org/gls/pdf/Prostate%20Cancer%202010%20June%2017th.pdf. Retrieved July 19, 2010. .

HIFU as a treatment option for prostate cancer is controversial among urologic experts, which is reflected in the differing guidelines concerning its use over the whole of Europe. However, HIFU is a promising new treatment option for prostate cancer, and its technology has been evolving over the past decade. Nevertheless, considering the biology and natural course of prostate cancer, the technology is too young and the follow-up of published series in the literature is inadequate to assess patient-relevant outcomes.

References in context

Fig. 1 shows the detailed literature selection process.
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Table 3 Ablatherm high-intensity focussed ultrasound: primary therapy

Study	Blana et al [18] x A. Blana, F.J. Murat, B. Walter, et al. First analysis of the long-term results with transrectal HIFU in patients with localised prostate cancer. Eur Urol. 2008;53:1194-1203 Abstract, Full-text, PDF, Crossref.	Poissonnier et al [27] x L. Poissonnier, J.-Y. Chapelon, O. Rouvière, et al. Control of prostate cancer by transrectal HIFU in 227 patients. Eur Urol. 2007;51:381-387 Abstract, Full-text, PDF, Crossref.	Colombel et al [34] x M. Colombel, L. Poissonnier, X. Martin, A. Gelet. Clinical results of the prostate HIFU project. Eur Urol Suppl. 2006;5:491-494 Abstract, Full-text, PDF, Crossref.	Lee et al [24] x H.M. Lee, J.H. Hong, H.Y. Choi, H.M. Lee, J.H. Hong, H.Y. Choi. High-intensity focused ultrasound therapy for clinically localized prostate cancer. Prostate Cancer Prostatic Dis. 2006;9:439-443 Crossref.	Blana et al [19] x A. Blana, B. Walter, S. Rogenhofer, W.F. Wieland. High-intensity focused ultrasound for the treatment of localized prostate cancer: 5-year experience. Urology. 2004;63:297-300 Crossref.	Walter et al [33] x B. Walter, S. Rogenhofer, W.F. Wieland, A. Blana. Combination from TUR-P and high-intensity focused ultrasound (HIFU) for the treatment of localized prostate cancer—experience with 70 patients. J Urologie Urogynakologie. 2004;11:5-10	Chaussy et al [21] x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. The status of high-intensity focused ultrasound in the treatment of localized prostate cancer and the impact of a combined resection. Curr Urol Rep. 2003;4:248-252 Crossref.	Thüroff et al [28] x S. Thüroff, C. Chaussy, G. Vallancien, et al. High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study. J Endourol. 2003;17:673-677	Chaussy et al [20] x C. Chaussy, S. Thüroff, C. Chaussy, S. Thüroff. Results and side effects of high-intensity focused ultrasound in localized prostate cancer. J Endourol. 2001;15:437-440 discussion 447–8 Crossref.	Gelet et al [23] x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high intensity focused ultrasound for the treatment of localized prostate cancer: factors influencing the outcome. Eur Urol. 2001;40:124-129 Crossref.	Chaussy et al [22] x C.G. Chaussy, S. Thüroff, C.G. Chaussy, S. Thüroff. High-intensive focused ultrasound in localized prostate cancer. J Endourol. 2000;14:293-299 Crossref.
Country	DE/FR: 2 centres	FR	FR	KR	DE	DE	DE	DE/FR/NL: 6 centres	DE	FR	DE
Patients, No.	140	227	242	58	146	70	271 (A: prospective: HIFU 96; B: retrospective: TURP + HIFU 175)	402	184	102	65 (A: global, n = NA vs B: selective treatment, n = NA)
Patients, age, yr (range)	M: 70 (45–87)	Ø 69 ± 6	Ø 71 ± 6	Ø 70 ± 6	Ø 70 ± 7	Ø 67 ± 6	A: Ø 66 ± 8; B: Ø 68 ± 7	Ø 70 ± 7	Ø 72 (59–81)	Ø 71 ± 6	NA
Tumour stage	T1a–T2cNxM0	T1–T2	T1cT2	T1–T2	T1–T2N0M0	T1–T2bN0M0	T1–T2c	T1–T2N0-NxM0	T1–T2NxM0	T1b–T2	Localised
Neoadjuvant ADT, % of pts	16	33	NA	29	43	NA	NA	0	NA	8	NA
TURP prior to/combined with HIFU, % of pts	NA	78	100	91	NA	100	65	NA	NA	NA	NA
Follow-up, mo (range)	Ø 77 ± 12	Ø 28 ± 20; M: 21 (12–107)	NA	Ø 14 ± 4	Ø 23 (4–62)	Ø 15 ± 7	A: Ø 19 ± 12, B: Ø 11 ± 6	Ø 14 (0–51)	Ø 6, M: 4 (0–30)	Ø 19 (3–76)	Ø 10 (1–18)

References in context

Study characteristics are shown in Table 3.
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Table 4 Evidence profile: Ablatherm high-intensity focussed ultrasound

No. of studies/patients	Study design	Methodological quality	Consistency of results	Directness of evidence	Magnitude of effect, %	Other modifying factors¹	Level of evidence
Outcome: biochemical disease-free survival rate
2/367	Observational, case series	Serious limitations² (−1)	No important inconsistency	Direct	66–77 at 5 yr, 69 at 7 yr	Publication bias likely	Very low

Outcome: negative biopsy rate
10/1849	Observational, case series	Serious limitations² (−1)	Important inconsistency	Direct	86 at 3 mo, 65–94 (point in time not specified)	Publication bias likely; lack of precise data	Very low

Outcome: overall survival rate
1/140	Observational, case series	Serious limitations² (−1)	Only one trial	Direct	90 at 5 yr, 83 at 8 yr	Publication bias likely	Very low

Outcome: prostate-cancer specific survival rate
1/140	Observational, case series	Serious limitations² (−1)	Only one trial	Direct	100 at 5 yr, 98 at 8 yr	Publication bias likely	Very low

Outcome: adverse events urinary tract³
4/702–11/1907⁴	Observational, case series	Serious limitations² (−1)	Important inconsistency	Direct	2–58	Publication bias likely	Very low

Outcome: adverse events potency⁵
8/1714	Observational, case series	Serious limitations² (−1)	Important inconsistency	Direct	18–0	Publication bias likely	Very low

Outcome: adverse events rectum⁶
1/184–6/969⁷	Observational, case series	Serious limitations² (−1)	Important inconsistency	Direct	0–15	Publication bias likely	Very low

Outcome: pain
6/927	Observational, case series	Serious limitations² (−1)	No important inconsistency	Direct	1–6	Publication bias likely	Very low

Outcome: IEFF (30-point scale)
No evidence

Outcome: IPSS (35-point scale)
4/671	Observational, case series	Serious limitations² (−1)	Important inconsistency	Direct	Improved by 1–4 points, or worsened by 3 points (baseline vs last follow-up)	Publication bias likely	Very low

Outcome: IPSS-Quality of Life (6-point scale)
3/525	Observational, case series	Serious limitations² (−1)	No important inconsistency	Direct	Changed by ±1 point (baseline vs last follow-up)	Publication bias likely	Very low

IEFF = International Index of Erectile Function; IPSS = International Prostate Symptom Score.

¹ Low incidence, lack of precise data, strong or very strong association, high risk of publication bias, dose-efficacy gradient, residual confounding plausible.

³ Adverse events urinary tract: bladder neck/urethral stricture/stenosis, prolonged urinary retention, urinary tract infection, urinary incontinence.

⁴ Not all adverse events concerning urinary tract were assessed in all studies.

⁵ Adverse events potency: impotence/erectile dysfunction.

⁶ Adverse events rectum: rectal burn, rectourethral fistula.

⁷ Not all adverse events concerning rectum were assessed in all studies.

References in context

Table 4 shows the evidence profile of Ablatherm HIFU as a primary therapy option in prostate cancer.
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Table 5 Ablatherm high-intensity focussed ultrasound: salvage therapy

Study	Colombel et al [34] x M. Colombel, L. Poissonnier, X. Martin, A. Gelet. Clinical results of the prostate HIFU project. Eur Urol Suppl. 2006;5:491-494 Abstract, Full-text, PDF, Crossref.	Gelet et al [36] x A. Gelet, J.Y. Chapelon, L. Poissonnier, et al. Local recurrence of prostate cancer after external beam radiotherapy: early experience of salvage therapy using high-intensity focused ultrasonography. Urology. 2004;63:625-629 Crossref.	Gelet et al [35] x A. Gelet, J.Y. Chapelon, R. Bouvier, et al. Transrectal high-intensity focused ultrasound: minimally invasive therapy of localized prostate cancer [published correction appears in J Endourol 2000;14:697]. J Endourol. 2000;14:519-528 Crossref.
Country	FR	FR	FR
Patients, No.	71	71	82
Patients, age, yr	NA	Ø 67 ± 6	Ø 71 ± 6
Tumour stage	Local recurrence	Local recurrence (T1–T3)	T1–T2
Primary treatment	EBRT	EBRT	EBRT
Neoadjuvant ADT, % of pts	NA	30	9
TURP prior to/combined with HIFU, % of pts	NA	NA	NA
Follow-up, mo (range)	Ø 15	Ø 15 (6–86)	Ø 18

References in context

Study characteristics are shown in Table 5.
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Table 6 Evidence profile: salvage high-intensity focussed ultrasound

No. of studies/patients	Study design	Methodological quality	Consistency of results	Directness of evidence	Magnitude of effect, %	Other modifying factors¹	Level of evidence
Outcome: biochemical disease-free survival rate
No evidence

Outcome: negative biopsy rate
3/224	Observational, case series	Serious limitations² (−1)	Important inconsistency	Direct	80 at 15 mo, 78–80 (point in time not specified)	Publication bias likely; lack of precise data	Very low
Outcome: overall survival rate
No evidence

Outcome: prostate-cancer specific survival rate
No evidence

Outcome: adverse events urinary tract³
1/82–3/224⁴	Observational, case series	Serious limitations² (−1)	Important inconsistency	Direct	1–35	Publication bias likely	Very low
Outcome: adverse events potency⁵
1/82	Observational, case series	Serious limitations² (−1)	Only one trial	Direct	77	Publication bias likely	Very low
Outcome: adverse events rectum⁶
3/224	Observational, case series	Serious limitations² (−1)	No important inconsistency	Direct	1–6	Publication bias likely	Very low
Outcome: pain
1/82	Observational, case series	Serious limitations² (−1)	Only one trial	Direct	1	Publication bias likely	Very low
Outcome: IEFF (30-point scale)
No evidence

Outcome: IPSS (35-point scale)
No evidence

Outcome: IPSS-Quality of Life (6-point scale)
No evidence

IEFF = International Index of Erectile Function; IPSS = International Prostate Symptom Score.

¹ Low incidence, lack of precise data, strong or very strong association, high risk of publication bias, dose-efficacy gradient, residual confounding plausible.

³ Adverse events urinary tract: bladder neck/urethral stricture/stenosis, prolonged urinary retention, urinary tract infection, urinary incontinence.

⁴ Not all adverse events concerning urinary tract were assessed in all studies.

⁵ Adverse events potency: impotence/erectile dysfunction.

⁶ Adverse events rectum: rectourethral fistula.

References in context

Table 6 shows the evidence profile of Ablatherm HIFU in the salvage setting in prostate cancer.
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Table 7 Sonablate high-intensity focussed ultrasound: primary therapy

Study	Ahmed et al [17] x Ahmed HU, Zacharakis E, Dudderidge T, et al. High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series. Br J Cancer 2009 7;101:19–26.	Mearini et al [25] x L. Mearini, L. D’Urso, D. Collura, et al. Visually directed transrectal high intensity focused ultrasound for the treatment of prostate cancer: a preliminary report on the Italian experience. J Urol. 2009;181:105-111 discussion 111–2	Uchida et al [32] x T. Uchida, S. Shoji, M. Nakano, et al. Transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer: eight-year experience. Int J Urol. 2009;16:881-886 Crossref.	Muto et al [26] x S. Muto, T. Yoshii, K. Saito, et al. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn J Clin Oncol. 2008;38:192-199 Crossref.	Uchida et al [31] x T. Uchida, H. Ohkusa, H. Yamashita, et al. Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer. Int J Urol. 2006;13:228-233 Crossref.	Uchida et al [30] x T. Uchida, H. Ohkusa, Y. Nagata, et al. Treatment of localized prostate cancer using high-intensity focused ultrasound. BJU Int. 2006;97:56-61 Crossref.	Uchida et al [29] x T. Uchida, S. Baba, A. Irie, et al. Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study. Hinyokika Kiyo. 2005;51:651-658
Country	GB: 2 centres	IT: 2 centres	JP	JP	JP	JP	JP: multicentre
Patients, No.	172	163	517	70 (A: full ablation 41; B: focal ablation 29)	181	63	72
Patients, age	Ø 64 ± 8 (47–88)	M (IQR): 72 (68–75)	M: 68 (45–88)	M: 72 (61–80)	M: 70 (45–88)	M: 71 (45–87)	M: 72 (45–79)
Tumour stage	≤T1c–T3bN0M0	T1c–T3aN0M0	T1c–T3N0M0	T1c–T2N0M0	T1c–T2bN0M0	T1c–T2bN0M0	T1c–T2bN0M0
Neoadjuvant ADT, % of pts	29	0	66	34	52	0	0
TURP prior to/combined with HIFU, % of pts	0	0	NA	NA	NA	0	NA
Follow-up, mo. (range)	Ø 12 ± 8 (5–25)	M: 24 (12–41)	M: 24 (2–88)	M: 34 (8–45)	M: 18 (4–68)	M: 22 (3–63)	M: 14 (2–24)

References in context

As shown in Table 7, between 63 and 517 patients were treated with Sonablate HIFU who were recruited consecutively in four case series [25,29,30,32].
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Table 8 Evidence profile of Sonablate high-intensity focussed ultrasound

No. of studies/patients	Study design	Methodological quality	Consistency of results	Directness of evidence	Magnitude of effect, %	Other modifying factors¹	Level of evidence
Outcome: biochemical disease-free survival rate
6/1066	Observational, case series	Serious limitations² (−1)	Important inconsistency		78–84 at 1 yr, 0–91 at 2 yr, 20– 6 at 3 yr, 45– 4 at 5 yr	Publication bias likely	Very low
Outcome: negative biopsy rate
5/885	Observational, case series	Serious limitations² (−1)	Important inconsistency		19–89 at 6 mo, 77–84 at 12 mo	Publication bias likely	Very low
Outcome: overall survival rate
No evidence

Outcome: prostate-cancer specific survival rate
No evidence

Outcome: adverse events urinary tract³
2/242–7/1238⁴	Observational, case series	Serious limitations² (−1)	Important inconsistency	Direct	1–30	Publication bias likely	Very low
Outcome: adverse events potency⁵
4/833–5/1005⁶	Observational, case series	Serious limitations² (−1)	Important inconsistency	Direct	1–39	Publication bias likely	Very low
Outcome: adverse events rectum⁷
1/72–5/1096⁸	Observational, case series	Serious limitations² (−1)	No important inconsistency	Direct	0–2	Publication bias likely	Very low
Outcome: pain
No evidence

Outcome: IEFF (30-point scale)
1/172	Observational, case series	Serious limitations² (−1)	Only one trial	Direct	Worsened by 6 points (baseline vs 12 mo post HIFU)	No	Very low
Outcome: IPSS (35-point scale)
4/671	Observational, case series	Serious limitations² (−1)	No important inconsistency	Direct	Changed by ± 1 point (baseline vs 12 mo post HIFU)	Publication bias likely	Very low
Outcome: IPSS-Quality of Life (6-point scale)
No evidence