High Intensity Focused Ultrasound for the Treatment of Prostate Cancer

Educational Objectives

The goal of this lecture is to improve the understanding and use of high intensity focused ultrasound (HIFU). After hearing and assimilating this lecture, the clinician will be better able to:

1. Review the clinical literature about HIFU and explain the applications of HIFU in men with prostate cancer.

2. Contrast HIFU with other modalities for treating prostate cancer.

Summary

Dilemma: in Germany, mean age of diagnosis of prostate cancer 72 yr in 1990, with life expectancy of 78 yr; now prostate cancer diagnosed at average age of 65 yr, with life expectancy extending to 82 yr; as more men live longer with diagnosis of prostate cancer, alternative treatments being sought

Initial trial: initial European multicenter trial of high intensity focused ultrasound (HIFU) found 86% negative biopsy rate in low-risk group, with median prostate-specific antigen (PSA) nadir of 0.4 ng/mL; high-risk patients in this study had 72% negative biopsy rate (similar success rate to that of radical prostatectomy)

Physical characteristics of HIFU: transrectal probe emits focused ultrasound beam that coagulates prostate; rectal wall protected by integrated cooling system; target area of prostate reaches temperature of ≈90ºC, which results in sudden coagulation and necrosis of exposed tissue; technology has continued to progress with regard to safety and imaging

Biochemical efficacy: German study of HIFU demonstrated PSA nadir of 0.1 ng/mL at 3 mo, with comparable PSA velocity between newer and older devices; with first prototype, 3 patients developed rectourethral fistula; newer models incorporate cooling system and other safety protocols; trials have also explored combining transurethral resection of prostate (TURP) with HIFU; study of ≈700 patients who underwent primary HIFU and followed for 14 yr found low-risk patients had recurrence-free rate of 96% to 98%, intermediate-risk patients 80%, and high-risk patients 70%; results comparable to those with radical prostatectomy; other centers have published similar findings

Applications: include locally advanced prostate cancer, incidental carcinoma, salvage therapy, focal therapy, palliative therapy for eradication of local tumor, and treatment of hormone-resistant prostate cancer

Incidental prostate cancer: study of 52 patients with incidental prostate cancer treated with HIFU demonstrated median PSA nadir of 0.06 ng/mL and PSA velocity reduced to 0.05 ng/mL

Protection of potency: HIFU excludes contralateral side of prostate, resulting in 75% to 95% rate of potency protection

Salvage therapy: 10 yr after radiation therapy, data show 63% of men have recurrent prostate cancer; 1/3 of patients have local recurrence only; patients with recurrent or residual tumors have significantly higher risk for progression and metastasis; study in United Kingdom of 84 men found salvage whole-gland HIFU to be promising for early cancer control; another study of 290 men with locally radiorecurrent prostate cancer who underwent salvage HIFU found 80% cancer-specific survival rate and 79.6% metastasis-free survival rate at 7 yr; speaker has also used HIFU for treatment of biopsy-proven recurrent cancer after radical prostatectomy, which avoids need for antihormonal therapy for those patients; salvage in hormone-resistant prostate cancer — study of 73 patients with PSA progression after hormone ablation treated with TURP and HIFU found PSA reduction of 80% with local disease and 65% with systemic disease

Palliative indications: primary goals — preventing tumor infiltration of rectum and bladder neck; delay of cell spread from primary tumor; destruction of locally nonhormone–sensitive tumor cells; avoidance of intravesical and supravesical obstruction; secondary goals — improve survival and quality of life; induce immunologic response; decrease cellular selection due to hormone ablation; German study of HIFU in patients with locally advanced prostate cancer over 5 yr found PSA nadir of 0.28 ng/mL and PSA velocity of 0.26 ng/mL/yr; 96% of patients did not require antihormonal therapy; data confirmed by group in Italy; speaker also reports 2 case examples of patients with metastatic disease treated with HIFU and hormonal ablation who had complete remission of disease at 10 yr; these case examples suggest HIFA might modulate immune response against prostate cancer

Focal therapy: HIFU for focal prostate cancer one alternative to active surveillance; active surveillance — has disadvantage of underestimating tumor stage and aggressiveness; 34% to 49% of cases undergraded and 10% to 13% of cases understaged; also involves significant patient anxiety, which triggers intervention; >30% of patients leave active surveillance within 3 yr and 50% leave by 10 yr; radical prostatectomy — Prostate Cancer Intervention vs Observation Trial (PIVOT) found that, among men with localized prostate cancer, radical prostatectomy did not reduce mortality compared to observation; in addition, radical prostatectomy often results in adverse events, such as impotence and incontinence; PIVOT results released around same time HIFU gained interest in lay press and touted by some as new treatment with “perfect” results; Japanese study showed HIFU to be feasible minimally invasive therapy for patients with low-risk localized prostate cancer and comparable to other modalities in control of cancer; study in United Kingdom of 39 men with localized prostate cancer treated with HIFU found 30 (77%) had negative biopsies after treatment

Conclusions: HIFU appears highly attractive as minimally invasive treatment for either primary or salvage therapy for prostate cancer; European clinical studies demonstrate HIFU’s feasibility for various indications with promising oncologic results and limited morbidity; development of devices with new ultrasound technology or magnetic resonance imaging guidance will increase role of this strategy in near future; proven results of HIFU’s efficacy now allow it to be incorporated into focal therapy, radical local primary therapy, and radical local salvage therapy

Readings

Ahmed HU et al: Focal salvage therapy for localized prostate cancer recurrence after external beam radiotherapy: a pilot study. Cancer 2012 Sep 1;118(17):4148-55; Chaussy CG, Thüroff S: Transrectal high-intensity focused ultrasound for local treatment of prostate cancer: current role. Arch Esp Urol 2011 Jul;64(6):493-50; Crouzet S et al: Whole-gland ablation of localized prostate cancer with high-intensity focused ultrasound: oncologic outcomes and morbidity in 1002 patients. Eur Urol 2014 May;65(5):907-14; Crouzet S et al: Locally recurrent prostate cancer after initial radiation therapy: early salvage high-intensity focused ultrasound improves oncologic outcomes. Radiother Oncol 2012 Nov;105(2):198-202; Ganzer R et al: Fourteen-year oncological and functional outcomes of high-intensity focused ultrasound in localized prostate cancer. BJU Int 2013 Aug;112(3):322-9; Kanthabalan A: Role of focal salvage ablative therapy in localized radiorecurrent prostate cancer. World J Urol 2013 Dec 31(6):1361-8; Muto S et al: Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn J Clin Oncol 2008 Mar;38(3):192-9; Thüroff S, Chaussy C: Evolution and outcomes of 3 MHz high intensity focused ultrasound therapy for localized prostate cancer during 15 years. J Urol 2013 Aug;190(2):702-10.

Disclosures

For this lecture, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Chaussy spoke at the 24th Annual Perspectives in Urology: Point Counterpoint, co-provided by Medical College of Wisconsin and Carden Jennings Publishing Co., Ltd. For more information about upcoming meetings organized by CJP Medical Communications in partnership with Grand Rounds in Urology, visit grandroundsinurology.com. The Audio Digest Foundation thanks Dr. Chaussy and the meeting sponsors for their cooperation in the production of this lecture.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

UR390402

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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