Download HIFU Articles - Rocky Mountain Urological Institute

First-line HIFU
2014: Whole-gland Ablation of Localized Prostate Cancer with High-intensity Focused Ultrasound:
Oncologic Outcomes and Morbidity in 1002 Patients
Sebastien Crouzet et al. - European Urology
"A total of 1002 patients were included. At 10 yr, the PCa-specific survival rate and metastasis-free
survival rate (MFSR) were 97% and 94%, respectively. Salvage therapies included external-beam
radiation therapy (EBRT) (13.8%), EBRT plus androgen-deprivation therapy (ADT) (9.7%), and ADT
alone (12.1%). Severe incontinence and bladder outlet obstruction decreased with refinement in the
technology, from 6.4% and 34.9% to 3.1% and 5.9%, respectively. HIFU is a minimally invasive
therapeutic option with encouraging cancer-specific survival rates in patients with localized PCa. The 10yr PCSMs and MFSRs were low, and the morbidity was acceptable. Salvage EBRT for post-HIFU relapse
was feasible, and the rate of patients requiring palliative ADT was low."
2013: Evolution and Outcomes of 3 MHz High Intensity Focused Ultrasound Therapy for Localized
Prostate Cancer During 15 Years
Stefan Thüroff and Christian Chaussy - 2013 The Journal of Urology
"The results in 704 patients show that HIFU offers men with localized PCa a standardized reliable therapy
with a low rate of perioperative comorbidity, an absence of serious morbidity and sufficient cancer control
such that salvage therapy was not required at 10-year follow-up by 99%, 72% and 68% of low,
intermediate and high risk patients, respectively, which is particularly important from a patient centered
perspective. PSA nadir was demonstrated to be the greatest predictor of biochemical failure and the
median PSA nadir has been 0.1ng/ml or less since 2000. PSA velocity was less than 0.1ng/ml but not
zero, resulting in a slow increase to a PSA of 0.29 ng/ml at 5 years. The 95% metastasis-free survival rate
at 10 years excludes TURP as a factor in metastatic spread in patients with localized prostate cancer and
represents the first published data to our knowledge that empirically refute this long-held assumption.
Combined with TUR, HIFU can provide low invasive complete local tumor ablation, substituting
surgery/cryotherapy or postponing radiation therapy or/and long-term ADT in elderly patients. The
presented data of 10-year outcomes may warrant the possible closing of the investigational phase of
HIFU."
2013: Fourteen-year oncological and functional outcomes of high-intensity focused ultrasound in
localized prostate cancer
Roman Ganzer et al - 2013 BJU International
"In conclusion, we report on a large consecutive patient series after primary HIFU for clinically localized
PCa with the longest follow-up in current literature. Our results improve the understanding of the
oncological efficacy, morbidity and side effects of primary HIFU. The study underlines that HIFU is a
therapeutic option for patients of advanced age, at low-to-intermediate risk and with a life expectancy of
~10 years. The rate of serious side effects such as recto-urethral fistulae is low."
2012: Complete high-intensity focused ultrasound in prostate cancer: outcome from the @Registry
Andreas Blana et al – Prostate Cancer and Prostatic Diseases
"Complete prostate-gland HIFU as primary monotherapy for localized prostate cancer is effective
oncologically in a subset of patients with small prostate as measured by post-therapy prostate biopsy and
serum PSA endpoints. In this study, HIFU is equally efficacious for all the grades of prostate cancer on
short-term follow-up. Careful evaluation of long-term HIFU efficacy is needed and should be compared
with established therapies with a complete HIFU approach to allow the most accurate evaluation of this
promising and novel technology."
2012: Single-session primary high-intensity focused ultrasonography treatment for localized
prostate cancer: biochemical outcomes using third generation-based technology.
Jehonathan H. Pinthus et al – BJU International
"In conclusion, 4-year oncological efficacy of single-session primary HIFU is promising in patients with
low- and intermediate-risk PC. Most cases of BCF occur in the first 2 years and are progressively less
common thereafter within the timeline of study. Patients with low- and intermediate-risk PC who achieve a
PSA nadir < 0.5 ng/mL have excellent 4-year biochemical failure free progression after a single session of
primary HIFU therapy. A prostate volume < 30 mL is associated with PSA nadir levels of < 0.5 ng/mL
which raises the question of whether planned pretreatment prostate volume reduction (medically or
surgically) should be considered in larger prostates."
2012: Single application of high-intensity focused ultrasound as a first-line therapy for clinically
localized prostate cancer: 5-year outcomes.
Dietrich Pfeiffer et al – BJU International
"Single-session HIFU is recommended as a curative approach in elderly patients with low-risk PCa.
Patients at higher risk of tumor progression should be counseled regarding the likely need for salvage
therapy, including repeat HIFU."
2011: Correlation of prostate-specific antigen nadir and biochemical failure after High-Intensity
Focused Ultrasound of localized prostate cancer based on the Stuttgart failure criteria – analysis
from the @-Registry.
Roman Ganzer et al – BJU International
"This multicentre analysis confirms that PSA nadir after HIFU predicts biochemical DFSR in a statistically
significant manner."
2010: Multicentric Oncologic Outcomes of High-Intensity Focused Ultrasound for Localized
Prostate Cancer in 803 Patients
Sebastien Crouzet et al. – European Urology
"Local control and DFSR achieved with HIFU were similar to those expected with conformal externalbeam radiation therapy(EBRT).The excellent cancer-specific survival rate is also explained by the
possibility to repeat HIFU and use salvage EBRT."
2008 : First Analysis of the Long-Term Results with Transrectal HIFU in Patients with Localised
Prostate Cancer
Andreas Blana et al. – European Urology
"This study demonstrates the effective long-term cancer control achieved using HIFU in patients with lowor intermediate-risk localized prostate cancer. We believed HIFU provides a potential treatment option for
localized prostate cancer in patients who are not eligible for surgery. The additional benefit of a favorable
morbidity profile should persuade clinicians to consider more patients for this curative option, which is, in
our opinion, a valid alternative to radiotherapy."
2006: Short-term outcome after high-intensity focused ultrasound in the treatment of patients with
high-risk prostate cancer
Vincenzo Ficarra et al. – BJU International
"HIFU is a minimally invasive therapy for prostate cancer often used in selected patients with localized
disease. The present results showed that HIFU combined with adjuvant pharmacological castration was
feasible also in patients with high-risk prostate cancer. The low complication rates, favorable functional
outcome and particularly the promising preliminary oncological data support the planning of further larger
studies in such patients. The oncological efficacy of the present protocol should be assessed in further
studies with more patients and a longer follow-up."
2006: Control of Prostate Cancer by Transrectal HIFU in 227 Patients
Laura Poissonnier et al. – Eur Urol.
"Transrectal HIFU is a minimally invasive therapy that control localized prostate cancer locally in 86% of
the cases. This therapy provided disease control in 66% of the patients with clinically confined prostate
cancer. Early feedback on treatment efficacy was gained by using nadir PSA (obtained within 4 months)
and random control biopsies."
2004: High Intensity Focused Ultrasound for the Treatment of Localized Prostate Cancer: 5-year
Experience
A. Blana et al. – Urology
"Our results demonstrated the efficacy and low-associated morbidity of HIFU. HIFU does not exclude
other treatment options and is repeatable. HIFU seems to be a valid alternative treatment for patients who
are not suitable for radical surgery."
2003: High-Intensity Focused Ultrasound and Localized Prostate Cancer: Efficacy Results from
the European Multicentric Study
S. Thüroff et al. – Journal of Endourology
"These short-term results obtained on a large cohort confirm that HIFU is an option to be considered for
the primary treatment oflocalized prostate cancer."
2001: Transrectal High-Intensity Focused Ultrasound for the Treatment of Localized Prostate
Cancer: Factors Influencing the Outcome
A. Gelet et al. – European Urology
"Results observed after HIFU treatment in localized prostate cancer are now challenging those obtained
after radiation therapy. The success rate is influenced by disease-related prognostic factors."
Focal HIFU
2015: A prospective clinical trial of HIFU hemiablation for clinically localized prostate cancer
Van Velthoven R et al. – Prostate Cancer and Prostatic diseases
"Over 8 years, hemiablation HIFU was primarily performed in 50 selected patients with biopsy-proven
clinically localized unilateral, low–intermediate risk prostate cancer in complete concordance with the
prostate cancer lesions identified by magnetic resonance imaging. The 5-year actuarial cancer-specific
survival rate was 100%, respectively. Complete continence (no pads) and erection sufficient for
intercourse were documented in 94 or 80% of patients, respectively. In conclusion, hemiablation HIFU
therapy, delivered with intention to treat, for carefully selected patients affords mid-term promising
functional and oncological outcomes. The effectiveness of this technique should be now compared with
whole-gland radical therapy.
2015: Focal High-intensity Focused Ultrasound Targeted Hemiablation for Unilateral Prostate
Cancer: A Prospective Evaluation of Oncologic and Functional Outcomes
Cordeiro E.Ret al. – European Urology
"Single-center prospective evaluation of HIFU hemiablation for unilateral organ- confined PCa was
performed from July 2009 through December 2013 in 71 patients treated by Hemiablation HIFU. Median
follow-up was 12 mo (IQR: 6–50 mo), and at 12 mo, 56 of 67 patients had a negative control biopsy in the
treated lobe. At 3 mo, all patients were continent. Complications included 8% Clavien–Dindo grade 2 and
2.8% grade 3 events. Conclusions: Focal HIFU hemiablation appears to achieve acceptable oncologic
outcomes with low morbidity and minimal functional changes. Longer follow-up will establish future
considerations.
2014: Primary Zonal High Intensity Focused Ultrasound for Prostate Cancer: Results of a
Prospective Phase IIa Feasibility Study
Van Velthoven R et al. – Prostate Cancer
"The role of focal therapy in primary treatment of prostate cancer is best described as experimental and
promising as progressively more and more studies are reporting good results. Our study suggests that
hemiablation HIFU is a valid focal therapy strategy, feasible in day-to-day practice with good promising
results. Well-designed, multicenter, prospective, randomized controlled studies are required to definitely
establish the role of hemiablation and focal therapies as the standard of care in prostate cancer. The
eventual success of these therapies, however, will depend not only on the form of focal therapy but also
mainly on technological advances in imaging and diagnostic techniques improving diagnostic and tumor
localization accuracy."
2014: Hemi salvage high-intensity focused ultrasound (HIFU) in unilateral radio-recurrent prostate
cancer: a prospective two-centre study
Baco E et al. – BJU International
"In conclusion, Hemi Salvage HIFU in patients with unilateral radiorecurrent prostate cancer results in
fewer and less severe morbidity than whole-gland salvage therapies, and may preserve pre-treatment
health-related quality of life. Accurate imaging and biopsy are essential to identify malignancy suitable for
focal therapy and to exclude metastatic disease. Based on the present results, prospective multicenter
clinical trials with long-term follow-up are warranted."
2011: Focal Therapy with High-Intensity Focused Ultrasound for Prostate Cancer in the Elderly. A
Feasibility Study with 10 Years Follow-Up.
Amine B. El Fegoun et al – Brazilian Journal of Urology
"This retrospective feasibility study shows that hemi-prostate ablation with HIFU is a reasonable treatment
strategy for a selected population of low or intermediate risk prostate cancer in elderly men. The longterm cancer control rate is adequate, recurrences can be treated with a second HIFU session or other
techniques. In the elderly, the concept of cancer control instead of cancer cure with HIFU has to be
discussed, as it seems to provide an effective long term disease control with minimal treatment-related
morbidity. More extensive biopsy protocols and more accurate imaging techniques will certainly improve
patients' selection. Larger prospective studies with a long follow-up are awaited to confirm our small size
preliminary results."
Salvage HIFU
2012: Locally recurrent prostate cancer after initial radiation therapy: Early salvage high-intensity
focused ultrasound improves oncologic outcomes
Sébastien Crouzet et al. – Radiotherapy and Oncology
"Salvage HIFU is an effective curative option for radiorecurrent PCa with acceptable morbidity for
localized radiorecurrent PCa, but should be initiated early following EBRT failure. Use of prognostic risk
factors can optimize patient selection."
2011: HIFU as salvage first-line treatment for palpable, TRUS-evidenced, biopsy-proven locally
recurrent prostate cancer after radical prostatectomy: A pilot study
Anastasios D. Asimakopoulos et al – Urologic Oncology 2011
"HIFU as salvage first-line treatment for palpable, TRUS-evidenced, biopsy-proven local recurrence of
CaP is a feasible, minimally invasive day-case procedure, with an acceptable morbidity profile. It seems
to have good cancer control in the short- and mid-term. Patients with lower pre-HIFU PSA level and
favorable pathologic Gleason score seem to present better oncologic outcomes. A prospective
randomized trial with an adequate recruitment and follow-up is necessary to confirm our preliminary
oncologic results."
2010: Salvage Radiotherapy After High-Intensity Focused Ultrasound for Recurrent Localised
Prostate Cancer
Julien Riviere et al. – European Urology
"After a preliminary study, our study has confirmed the feasibility of radiation therapy following HIFU. On
the basis of oncologic outcome plus acceptable toxicity, SRT can be considered a treatment option for
HIFU failures. Oncologic results will be addressed with a longer follow-up."
2010: A prospective study of salvage high-intensity focused ultrasound for locally radiorecurrent
prostate cancer: Early results
VIKTOR BERGE et al. – Scandinavian Journal of Urology and Nephrology
"In conclusion, early results of salvage HIFU in patients with local recurrence of prostate cancer after
radical EBRT indicate the procedure to be a reasonable treatment option, but better patient selection
criteria are still requires. However, the side-effects are not negligible."
2008: Mid-term Results Demonstrate Salvage High-Intensity Focused Ultrasound (HIFU) as an
Effective and Acceptably Morbid Salvage Treatment Option for Locally Radiorecurrent Prostate
Cancer
François-Joseph Murat et al. – European Urology
"Salvage HIFU is a promising treatment option for local relapse after RT failure. This retrospective
analysis shows high local tumor control. Favorable 5-yr outcomes are expected if HIFU is performed for
low-risk or intermediate-risk patients. There are acceptable morbidity rates and especially nu URF with
the specific post-radiation parameters. [...] Future advances in technology and safety will undoubtely
expand the HIFU role in this indication."
2006: Recurrent Prostate Cancer After Radiotherapy – Salvage Treatment by High Intensity
Focused Ultrasound
F-J. Murat et al. – European Oncological Disease
"Treatment with HIFU allowed local tumor control in 84% of patients treated for prostate cancer
recurrence after radiotherapy, but disease control depended on initial risk factor and Gleason score at the
time of recurrence. High-risk patients (T3 or PSA >20 or Gleason score ?8) are not good candidates for
salvage treatment with HIFU: they must be strictly selected (18F-fluorocholine PET scan) as the majority
have silent metastases associated with local recurrence. Conversely, treatment with HIFU is a very
interesting curative option for low- or intermediate-risk patients, particularly if the Gleason score of the
local recurrence is ?7."
2000: Transrectal High Intensity Focused Ultrasound: minimally invasive therapy for localized
Prostate Cancer.
Gelet et al. – Journal of Endourology
"Transrectal HIFU prostate ablation is an effective therapeutic alternative for patients
with localized prostatic adenocarcinoma."
Review article
2011: Robotic High-intensity Focused Ultrasound for Prostate Cancer: What Have We Learned in
15 Years of Clinical Use?
Christian Chaussy et al – Current Urology Report
"Since 2000, HIFU by Ablatherm is a non-experimental therapy under long-term investigation for primary
treatment of local prostate cancer as well as salvage therapy after radiation failure. It appears to have a
high potential to treat on either side of this spectrum in focal and in incidental prostate cancer as well as
adjuvant in T3/T4 disease or in non-metastatic hormone-resistant prostate cancer. The versatility of HIFU
appears to be unique in the treatment of the entire spectrum of prostate cancer, which is a multifaceted
increasing and long-lasting disease. HIFU does not substitute or is not competitive to only one classical
therapy, but its indications overlap in a certain range with all therapies. As additional local one-session
tumor debulking therapy..."
2008: High-intensity focused ultrasound in prostate cancer; a systematic literature review of the
French Association of Urology
Xavier Rebillard et al. – BJU International
"In patients selected [...], HIFU results in short-term cancer control, as shown by a high percentage of
negative biopsies and substantially decreased PSA levels. Median-term DFS data (with the Ablatherm
device) seem promising. With the continuous development of the Ablatherm device and the use of TURP
before HIFU, the rate of HIFU-related complications has decreased. Recent studies show that HIFU is
well tolerated, with a low rate of complications that compare favorably with those after established
therapies. Longer-term follow-up studies are needed to further evaluate cancer-specific and overall
survival rates."
2006: High Intensity Focused Ultrasound for Prostate Cancer: A Review of the Scientific
Foundation, Technology and Clinical Outcomes
John C. Rewcastle et al. – Technology in Cancer Research and Treatment
"High intensity focused ultrasound is a technologically advanced non-invasive therapy for prostate cancer.
There currently exist two commercially available treatment units each with their own merits. Longer followup is available with the Ablatherm device, which also has demonstrated high local disease control in
multicenter investigations. The role of HIFU will continue to be defined as more patient series are
published with longer term follow-up."
2005: Technology insight: High-intensity focused ultrasound for urologic cancers.
Chaussy C et al. – Nat Clin Pract Urol
"The latest published results suggest that HIFU treatment is a valuable option for well-differentiated and
moderately-differentiated tumors, as well as for local recurrence after external-beam radiation therapy."
Morbidity
2011: Health-related quality of life after salvage high-intensity focused ultrasound (HIFU)
treatment for locally radiorecurrent prostate cancer
Viktor Berge et al. – International Journal of Urology
"Treatment of localized radiorecurrent PCa by salvage HIFU is associated with clinically significant
reductions in urinary and sexual function domains after a mean follow-up of 17.5 months."
2007: Factors Predicting for Formation of Bladder Outlet Obstruction After High-Intensity Focused
Ultrasound in Treatment of Localized Prostate Cancer
Andreas Blana et al. – Journal of Urology
"In our study, the occurrence of BOO after HIFU was significantly associated statistically with older age.
Surprisingly, TURP before HIFU was not an independent factor in the prevention of BOO during followup. However, the occurence of multiple BOO episodes could be reduced by resecting more tissue with
TURP before HIFU."
2006: Morbidity associated with repeated transrectal high-intensity focused ultrasound treatment
of localized prostate cancer
Andreas Blana et al. – World Journal of Urology
"Additional HIFU treatments in case of primary treatment failure for patients with localized prostate cancer
are associated with only a minor increase in morbidity. However the forthcoming aim will be to lower the
rate of patients with residual cancer after initial HIFU treatment by refined patient selection and more
effective treatment modalities."
2003: The Status of High-Intensity Focused Ultrasound in the Treatment of Localized Prostate
Cancer and the Impact of a Combined Resection
C. Chaussy et al. – Current Urology Reports
"The combination of a TURP and HIFU treatment reduces the treatment-related morbidity significantly.
The patient management after a combined TURP and HIFU treatment is comparable with the
management after a single TURP."
Technical Background
1999: High-intensity focused ultrasound (HIFU) followed after one to two weeks by radical
retropubic prostatectomy: results of a prospective study.
Beerlage HP et al. – Prostate
"Histology reports of radical prostatectomy specimens of patients operated 7-12 days
after HIFU treatment showed marked and complete necrosis in the treated area."
1999: Treatment of localised prostate cancer with transrectal high intensity focused ultrasound.
Chapelon JY et al. – Eur J Ultrasound
"The quality of HIFU treatment depends on four factors: the intensity of the transmitted pulse, the
exposure time, the signal frequency, and the time between two firing bursts. The lesions are created by a
thermal effect. Their slightly conical form is due to the absorption of ultrasound by tissue, enhanced by
cavitation bubbles."