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Cancer de la prostate

 

Qu’est-ce que le cancer de la prostate et comment est-il traité?

Le cancer de la prostate est le quatrième cancer le plus commun, hommes et femmes combinés et le 2ème plus fréquent chez l’homme. On estime à 1,1 million le nombre de cancers de la prostate diagnostiqués dans le monde en 2012, totalisant 15% des cancers diagnostiqués chez l’homme, dont près de 70% des cas (759 000) dans les régions les plus développées. Avec environ 307 000 décès en 2012, le cancer de la prostate est la cinquième cause de décès par cancer chez les hommes (6,6% des décès toute causes confondues). (Source : organisation Mondiale de la Santé, GLOBOCAN 2012)

 

Introduction

La prostate


La prostate est une glande de l'appareil génital masculin de la grosseur d'une châtaigne. Sa taille et son poids varient selon l'âge du patient. Située sous la vessie, devant le rectum, la glande prostatique entoure la partie supérieure de l'urètre (canal qui transporte l'urine de la vessie vers l'extérieur du corps). Elle participe au mécanisme de l'éjaculation, puisqu'elle sécrète la majeure partie du liquide séminal qui sert de moyen de transport et d'activation des spermatozoïdes.

 

1 - Pénis
2 - Urètre
3 - Testicule
4 - Scrotum
5 - Vessie
6 - Vésicule séminale
7 - Prostate
8 - Anus
9 - Rectum

Le cancer de la prostate

L'agressivité du cancer de la prostate est variable : certains cancers évoluent de façon lente et asymptomatique, tandis que d'autres évoluent rapidement vers l'envahissement loco-régional et métastatique. La probabilité de survenue du cancer de la prostate augmente avec l'âge. Dans les stades précoces de la maladie il n'y a généralement pas de signe ou symptôme et ceux-ci apparaissent en fonction de la localisation du cancer et de son extension. Le cancer de la prostate est considéré comme « localisé » lorsqu'il se situe exclusivement dans la glande prostatique.
Classification du Cancer de la prostate
T1 - T4 Prostate Cancer

Cancer localisé de la prostate (Stades T1 ou T2) : la tumeur est intracapsulaire, c'est à dire confinée à la prostate (intra-capsulaire)

  • Stade T1 : Il n'y a que quelques cellules cancéreuses et le cancer ne peut donc être diagnostiqué qu'avec un prélèvement sanguin ou une biopsie. Le cancer n'est pas décelable lors d'un toucher rectal.
  • Stade T2 : Le cancer est un peu plus gros et la glande durcit. Le médecin peut désormais déceler le cancer lors d'un toucher rectal.

Adénocarcinome de la prostate localement avancé (stades T3 et T4) : la tumeur s'étend aux organes adjacents

  • Stade T3 : La tumeur a franchi les limites de la glande.
  • Stade T4 : Le cancer de la prostate s'est propagé en dehors de la glande et potentiellement vers d'autres organes.

Dépistage et Diagnostic

Les chances de guérison en cas de diagnostic précoce d'un adécarcinome de la prostate sont très élevées. Le cancer de la prostate peut être détecté lors d'examens de routine. Le médecin procède à un examen de la prostate par toucher rectal pour déceler toute anomalie tel que la présence d'un nodule dur ou une augmentation de taille. Le médecin procède également à un prélèvement sanguin pour déterminer le taux d'antigène prostatique spécifique (PSA). Certains cancers sont aussi décelés lors de tests ou interventions pour l'hypertrophie bénigne de la prostate (HBP ou adénome de la prostate).
 
L'urologue peut procéder à différents tests pour confirmer le diagnostic de cancer de la prostate :
  1. Biopsies de la prostate : prélèvement de tissu prostatique à l'aide de fines aiguilles à des fins d'analyse.
  2. IRM ou scanner : imagerie de tous les organes pour détecter un éventuel cancer dans les ganglions pelviens, le foie ou d'autres organes.
  3. Scintigraphie osseuse ou TEP-scan : imagerie par injection d'un traceur pour rechercher une possible extension métastatique osseuse.

Traitement du cancer localisé de la prostate

Chirurgie (prostatectomie radicale)
On retire la totalité de la prostate ainsi que les vésicules séminales, les canaux déférents (conduisant le sperme), une partie du col de la vessie et les ganglions avoisinants. Cette intervention chirurgicale est complexe et nécessite une anesthésie générale de 3 à 4 heures.

Radiothérapie externe
Elle consiste à irradier la région prostatique avec des rayons ionisants de très haute énergie. La radiothérapie ne nécessite pas d'anesthésie et le traitement se déroule en général lors de séances réparties sur plusieurs semaines.

Curiethérapie (ou brachythérapie)
Cette technique consiste à placer de minuscules grains radioactifs dans la prostate de manière à irradier et détruire les cellules cancéreuses.

Cryothérapie
La cryothérapie est une technique basée sur l'implantation dans la prostate de fines aiguilles générant un froid important qui congèle les tissus et détruit les cellules tumorales. Le traitement est réalisé sous anesthésie et nécessite une hospitalisation d'une nuit au moins.

Ultrasons focalisés de haute intensité (HIFU)
La technologie HIFU est un traitement non-invasif du cancer localisé de la prostate par ultrasons focalisés. Cette focalisation produit une chaleur intense et provoque la destruction du tissu à l'intérieur de la zone ciblée. Le traitement dure une à trois heures et peut être réalisé sous anesthésie générale ou loco-régionale.

Traitement HIFU

Comment se déroule le traitement?

Le traitement s’effectue par voie endo-rectale sous anesthésie générale ou loco-régionale. Une sonde est placée dans le rectum et le transducteur d’imagerie commence à scanner la glande pour permettre au médecin de définir la zone à traiter. La sonde émet un faisceau d’ultrasons convergents de haute intensité dans la glande. A l’endroit où les ultrasons se concentrent, l’absorption soudaine et intense du faisceau ultrasonore crée une élévation quasi immédiate de la température  (entre 85 et 100°C), qui détruit toutes les cellules situées dans la zone cible.

Qui peut bénéficier du traitement par Ultrasons Focalisés ?

l'HIFU est indiqué pour :
  • Traitement de première intention pour les patients T1-T2 pour qui la chirurgie n'est pas possible ou qui la refuse
  • Traitement de rattrapage chez les patients présentant une récidive locale après radiothérapie externe, curiethérapie ou prostatectomie radicale
  • Traitement focal d'une tumeur bien localisée et définie à la fois en première intention et en traitement de rattrapage

 

Le traitement est-il douloureux ?

En lui-même le traitement n'est pas douloureux car il est réalisé sous anesthésie loco-régionale ou générale. Les suites du traitement ne sont pas douloureuses mais les patients ressentent un léger inconfort qui se dissipe au bout de quelques heures. Le traitement étant non-invasif, il n'y a pas de cicatrice et aucune sensation de brûlure habituellement associée à la radiothérapie.

Quel est le suivi après traitement ?

Une simple surveillance du PSA tous les 3 mois est suffisante. 6 mois ou 1 an après le traitement, des biopsies de contrôle peuvent être réalisées sous anesthésie locale. Si un foyer cancéreux résiduel est détecté (environ 10 à 15% des cas), une 2ème séance peut être proposée à partir de 6 mois après la séance initiale. Les autres options thérapeutiques (chirurgie, radiothérapie) restent envisageables.

Quelle est l’efficacité et la qualité de vie après le traitement HIFU ?

Les techniques médicales non-invasives visent à procurer le même niveau d'efficacité clinique que les techniques traditionnelles sans les inconvénients inhérents à celles-ci en terme de qualité de vie du patient. Les résultats cliniques collectés depuis plus de 15 ans montrent que la technologie HIFU entre parfaitement dans cette catégorie avec un excellent rapport bénéfices/risques :
  • Efficacité : les publications parues depuis 2000 - année du marquage CE de l'Ablatherm® HIFU – montrent des résultats reproductibles et constants avec des taux de survie à long terme comparables à ceux du traitement standard du cancer de la prostate
  • Le traitement de rattrapage par HIFU montre des résultats encourageant avec 80% de biopsies négatives et un taux de survie spécifique à 5 ans de 78% et 49,5% respectivement pour les patients à risques faible et intermédiaire.
  • Qualité de vie : l'analyse de la littérature scientifique parue depuis 2000 montre que le traitement HIFU est un excellent outil pour la préservation de la qualité de vie avec une faible morbidité et peu d'effets indésirables.

Quels sont les effets indésirables ?

Les études sur le traitement HIFU ont révélé peu d'effets indésirables. Les cellules saines avoisinantes ne sont pas détruites en même temps que les cellules cancéreuses de la zone cible et la procédure est non-invasive (ne nécessite pas d'incision). La durée du séjour à l'hôpital est donc raccourcie et le retour à une activité normale se fait après seulement quelques jours.
Les effets indésirables constatés sont : l'incontinence, la rétention urinaire, l'infection de l'appareil urinaire et la dysfonction érectile. Les effets indésirables du traitement HIFU se comparent avantageusement à ceux des thérapies plus invasives, en particulier pour un traitement focal.
Articles

Traitement en première intention par 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 10-yr 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 followup 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 external-beam 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 low- or 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."

Traitement focal par 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 long-term 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."

Traitement de rattrapage par 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."

Revues de la littérature

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 follow-up 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."

Morbidité

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 follow-up. 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."

Fondements techniques

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."

Résumés & Posters

Traitement en première intention par HIFU

2014: United States Experience with Primary HIFU Therapy for Patients with Low-Risk Prostate Cancer: Results of the Enlight Trial
Robertson C. et al. – FUSF
"Both the local (biopsy) control and the biochemical survival rates are promising following HIFU which was utilized as a single session monotherapy without any adjuvants. The adverse event profile demonstrates promising erectile function preservation and low rates of long term morbidity. These results complement the long term outcomes seen from Europe where HIFU is not infrequently used in combination with adjuvants and for multiple sessions as well as salvage HIFU procedures. HIFU for localized prostate cancer was confirmed in this study to be a viable treatment of prostate tissue and prostate neoplasia."

2014: Radical Prostatectomy versus High Intensity Focused Ultrasound for localized prostate cancer: A Matched Pair Comparison
Crouzet S. et al. – AUA_OP3-12
"At 9 years, the rate of patients who need palliative ADT, the overall cancer specific and metastasis free survival rates were not significantly different between HIFU and RP."

2014: Does Age represent a limitation for HIFU treatment? Age stratified outcomes from a multicentre study of 2762 patients analysed from the @-Registry
Crouzet S. et al. – AUA_MP62-04
"At 10 years the overall survival rates (<70 yrs / >70yrs) was significantly different: 85% /74% (p<0.0001), but the cancer specific survival and the metastasis free survival rates (<70 yrs / >70yrs) were not significantly different: 98%/98% (p=0.975) and 94%/94% (p=0.784). [...] HIFU presents positive oncological and functional outcome in patients both below and above 70 years. HIFU treatment might be therefore a valuable therapeutic option for prostate cancer control regardless of age. "

2014: External Beam Radiation Therapy versus High Intensity Focused Ultrasound for localized prostate cancer: A Matched pair comparison
Crouzet S. et al. – AUA_MP62-02
"The five years progression free survival rate was not significantly different between HIFU and EBRT but the rate of patients who need palliative S-ADT was significantly higher for EBRT compare to HIFU."

2014: High Intensity Focused Ultrasound in Prostate Cancer. Multicentric, Long Term Retreatment Rate Decrease
Thueroff S. et al. – AUA_MP46-11
"Technical development and adjuvant TUR before HIFU since 2000 resulted in higher local efficacy and lower HIFU retreatment rates of latest 10% since use of Ablatherm integrated imaging. Moment of detection of recurrent/residual PCa by PSA and biopsies was within the first year after 1st HIFU."

2013: Limitation of the current criteria for biochemical recurrence (BCR) after high intensity ultrasound (HIFU) in localized prostate cancer.
Sanchez-Salas R. et al. – EAU_MP589
"Actual criteria for BCR definition for HIFU patients are probably not adjusted to show the real disease behavior. PSA bouncing needs to be considering to state an improved BCR definition. Significant differences between salvage treatment and BCR definitions show the limitations of today´s criteria."

2013: HIFU treatment outcomes for localized prostate cancer from the first European centers
Crouzet S. et al. – AUA_MP50
"The biochemical survival rate achived with HIFU at 10 years is encouraging and negative biopsy rates are high across all risk groups. Ablatherm® HIFU treatment appears as a valuable therapy for long term prostate cancer control."

2013: Radical HIFU in Localized Prostate Cancer
Chaussy C. et al. – WCE_MP10-14
"TURP before HIFU resolves technical restrictions, expands indications, standardizes any prostate, but does not resolve the problem of secondary TURP for fibro-stenotic tissue within the prostate. PSA Nadir <0.1 ng/ml, PSA velocity/year of 0.05, last median PSA levels after 5 years of 0.3 ng/ml showed a high oncological efficacy. Retreatment rate for recurrent PCa decreased to 15% within the last 5 years."

2012: High intensity focused ultrasound at 3 MHz delays onset of androgen deprivation therapy in locally advanced prostate cancer
Chaussy C. et al. – EAU_MP888
"TUR & HIFU ablation in this T3-4, N0, M0 PCa cohort of 131 patients resulted in an overall PSA Nadir of 0.28 ng/ml and a median PSA velocity of 0.26 (ng/ml/year). Until a mean follow up of 3 years, 95.5 % of the patients remained without ADT. Level of initial PSA showed again to be a significant predictive value for therapy success."

2012: Oncological outcomes of high-intensity focused ultrasound for localized prostate cancer in 1098 consecutive patients
Crouzet S. et al. – EAU_MP980
"Local control and disease free survival rates achieved with HIFU were similar to those expected with conformal external beam radiation therapy with at 10 years a specific and metastasis survival rate of 98% and 94% respectively. HIFU can be repeated when necessary and is not a therapeutic impasse: it can also be associated to a salvage radiation therapy, which will lead to excellent prostate cancer control results."

2011: 10 year outcome and morbidity of High Intensity Focused Ultrasound (HIFU) as a primary therapy for localized prostate cancer: outcomes from 2552 men followed with the @-Registry
Ganzer R. et al. – AUA_MP1004
"HIFU provides good biochemical control through 10 years of follow-up with a mild morbidity profile. Negative biopsy rates are high across all risk groups. These long term outcomes represent HIFU emerging from investigational status to become a standard primary treatment option."

2011: Outcomes of HIFU for prostate cancer in 880 consecutive patients
Crouzet S. et al. – EAU
"Local control and disease free survival rates achieved with HIFU were similar to those expected with conformal external beam radiation therapy. HIFU can be repeated when necessary and is not a therapeutic impasse: it can also be associated to a salvage radiation therapy which will lead to excellent prostate cancer control results."

2011: Castration Resistant Prostate Cancer treated with TURP and High Intensity Focused Ultrasound at 3 MHz: A new tool for cancer control
Chaussy C. et al. – WCE
"TURP & HIFU in CrPCa reduced PSA by 84% and resulted in a median PSA velocity of 2.95ng/ml/year. 1/3 did not receive further ADT. 2/3 rd of the patients were still alive after a follow up of 2 years and had a PSA below entry PSA at treatment onset."

Traitement focal par HIFU

2015: Hemiablation HIFU treatment for unilateral localized prostate cancer: final results of the French Association of Urology
Rischmann P et al. – AFU

"A total of 110 patients were treated by Hemi-HIFU at 10 French centers. The rate of residual clinically significant cancer in the treated lobe was 5% after Hemi-HIFU and the survival rate without additional definitive treatment was 89% at 2 years. Urinary and sexual function preservation were 97% and 78% respectively. In conclusion, Hemiablation treatment with HIFU is feasible with very few side effects and the rate of additional definitive treatment is low (11% at 2 years)."

2015: Focal treatment of prostate cancer using Focal One device: pilot study results
Pasticier G et al. – ASCO GU

"To evaluate the ef¬ficacy of Focal One® device for focal treatment of localized prostate cancer. Ten patients with mono focal prostate cancer were treated between March 2013 and January 2014 using a 6 mm safety margin around the tumor. Early control biopsies guided with contrast-enhanced Ultrasound imaging were achieved one month after HIFU inside and in the rime of the treated area. In all patients, targeted biopsies inside the treated area performed at day 30 after the HIFU session demonstrated a complete destruction of the targeted tumor. All patients were potent and continent after 1 year follow-up. Focal One device is able to achieve a precise and complete destruction of prostate cancer focus using an elastic MR-US registration system for tumor location and HIFU treatment planning."

2014: Focal therapy with HIFU for localized prostate cancer: a prospective multicenter study
Rischmann P. et al. – EAU_MP358

"This multicenter study confirms the short term efficacy of HIFU focal therapy in patients with localized prostate cancer, with a very low morbidity profile and the possibility to repeat HIFU if necessary. Longer Follow-up is needed. Progress in imaging will help to improve selection and follow-up of patients."

2014: NERVE SPARING HIFU: Clinical Experience with the EDAP Ablatherm® Device
Chinn D. et al. – Focal Therapy and Imaging_PP36
"The technique of subtotal gland ablation appears to be effective in preserving sexual function while providing excellent PSA control. While there can be more side effects in comparison to focal therapy, the risk of leaving occult or potential prostate cancer tissue untreated is less. The cohort is quite small and follow up is less than 10 years. Further studies are required to validate the true potential of the nerve sparing HIFU, in particular, utilizing subtotal gland ablation."

2014: Focal HIFU (Focal One®) treatment of localized prostate cancer diagnosed with MRI-ultrasound fusion targeted biopsies (Koelis®): preliminary results
Nevoux P. et al. – Focal Therapy and Imaging_PP29

2013: Tolerance and efficacy of High Intensity Focused Ultrasound (HIFU) focal therapy as primary treatment for localized prostatic carcinoma: preliminary results
Conort P. et al. – Focal Therapy and Imaging_PP37
"The follow-up without systematic Prostate Biopsy seemed to be a safe option. The PB at 24 months for all patients is expected to confirm these initial results. HIFU-FT is very well tolerated with preliminary encouraging oncological results. A longer follow-up is required to confirm the benefit of the HIFU-FT and the safety of this method of follow-up."

2012: Nerve sparing HIFU as primary "focalized" treatment for localized prostate cancer : a single center study of 158 man with 7 years of follow up
D'Hont C. et al. – EMUC_PO88
"Nerve sparing HIFU (Less ablation) provides good biochemical control through > 7 years of follow-up combined with a relatively low rate of side effects = excellent QOL and good cancer control (same Quality of Treatment) in well selected patients. With more reliable imaging techniques more focalized HIFU treatment becomes a possible and safer first choice treatment in patients with limited and more focalized prostate cancer concerned about their Quality Of Life after treatment, knowing that in case of a local recurrence all salvage options (2nd HIFU & all other treatments) still remain possible."

2012: Hemi salvage HIFU in patients with radio-recurrent prostate cancer
Baco E. et al. – Focal Therapy and Imaging
"Hemi-salvage HIFU is efficient in patients with unilateral radio-recurrent prostate cancer with a preserved QoL. It may offer comparable cancer control to whole gland treatment."

Traitement de rattrapage par HIFU

2015: External beam radiation therapy or high intensity-focused ultrasound for localized prostate cancer: a matched pair analysis in PSA era
Pasticier G et al. – ASCO GU

"The aim of this study was to evaluate the oncologic outcome of patients treated with HIFU versus conformal external beam radiation therapy (C-EBRT) without previous or associated androgen deprivation (AD). 190 matched pair patients (95 patients in each arm) were prospectively followed. The progression free survival rate was not significantly different after HIFU than after C-EBRT but the rate of patients who need palliative S-ADT was significantly lower after HIFU than after C-EBRT: 15% versus 42%.

2012: Multicentric oncologic outcomes of salvage HIFU for local failure after external beam radio therapy: 7 years biochemical survival of 929 patients
Crouzet S. et al. – EAU_MP982

"Salvage HIFU is an effective secondary local treatment option for radiorecurrent PCa with curative objective and acceptable rate of morbidity. When indicated, S-HIFU must be performed quickly after an EBRT failure especially for patient previously treated with androgen deprivation. Predictive parameters can be used in the selection of eligible patients."

2011: Biochemical survival of 596 patients treated with salvage HIFU after failed external beam radiation tracked with the @-registry and stratified by PSA and pre-treatment hormone usage
Crouzet S. et al. – EAU
"Patients with recurrent disease following radiation therapy represent a difficult population to manage as the disease is aggressive and metastases are often microscopic and occult. These outcomes demonstrate that HIFU should be considered the standard treatment in the event of recurrence. Those patients treated first with hormone therapy had poorer outcomes than those treated immediately with HIFU. Early detection of radiation failure and prompt treatment with HIFU is recommended as a definitive local therapy with curative intent."

2011: Treatment of locally recurrent prostate cancer after External Beam Radiation Therapy (EBRT): Factors Predicting Oncological Outcome of Salvage High Intensity Focused Ultrasound (HIFU)
Crouzet S. et al. – USANZ
"Patients most likely to benefit from an HIFU salvage therapy have pre-RT low or intermediate disease. Results are better in patients with pre HIFU PSA values <4ng/ml which suggest that HIFU salvage treatment must be considered as soon as possible after the local recurrence."

2010: HIFU following failed Radiation Therapy: Biochemical Survival of Ablatherm Registry
Ward J. et al. – AUA_MP463
"The management of patients following radiation therapy is difficult. Four years after salvage HIFU 55% of patients remained biochemically disease free and 73.8% showed no evidence of local recurrence on follow-up biopsy. These results are encouraging and show the ability to return patients to disease free status following failed radiation therapy."

2010: Salvage High Intensity Focused Ultrasound (HIFU) for the Treatment of Locally Recurrent Prostate Cancer after External Beam Radiation Therapy (EBRT): factors influencing the outcome
Murat F.J. Et al. – EAU
"Salvage HIFU is a valid and effective treatment option for low and intermediate pre-EBRT risk group patients presenting with local recurrence after EBRT. Salvage HIFU is more effective when intended as soon as possible with PSA at the time of the recurrence under 4ng/ml. The PSA nadir post-HIFU is the major predictive factor of success."

2010: HIFU as a salvage treatment method for PCa local recurrence after radical prostatectomy
Alayev U. et al. – EAU
"Monotherapy salvage HIFU after radical prostatectomy failure is promising for its minimal invasiveness, low complications risk and absence of toxicity. Further development of special HIFU planning and performing techniques is needed in order to achieve good oncological results."

Morbidité

2014: Classification and Endoscopic Repair of Prostatic Urethral Obstruction after HIFU
Stefan Thueroff et al. – AUA_MP13-11
"Post-HIFU obstruction after TURP & HIFU is common and mostly correlated to small prostates and good oncological outcome. HIFU induced shrinkage of the prostatic capsule induces intracapsular „sand glass" type stenosis in 3 different locations and occurs typically 6-9 months after ½ a year of asymptomatic micturition. In contrast obstruction caused by necrotic tissue occurs early and does not have the interval of asymptomatic micutrition. „Endo-V-plastic" showed to be a simple and fast repair for stenosis repair, cold-loop curettage the adequat therapy for necrotic tissue resection."

2012: High Intensity Focused Ultrasound at 3MHz in localized prostate cancer: Side effects of 704 patients within 10 years
Stefan Thueroff et al. – EAU_MP978
"A low number of severe side effects was registered. TUR did decrease the overall side effect rate (catheter time, UTI, sludging) but not the 2ndary reintervention rate (obstruction): ¼ of the patients needed 2nd endourological intervention (at month 6-12). The spectrum of "potential side effects, which never occurred" shows the low invasiveness of the procedure."

2011: Can splitting TURP and HIFU in two session reduce complication rate ?
Roberto Sanseverino et al. – AUA_MP1299
"Splitting TURP and HIFU in two different sessions seems to reduce postoperative complications and improve patient tolerance of the procedure. Longer follow up and larger patient population are needed to obtain more robust evidence."

2011: Health-related quality of life after salvage high intensity focused ultrasound treatment (HIFU) for locally radiorecurrent prostate cancer
Viktor Berge et al. – EAU
"Treatment of localized radiorecurrent CaP by salvage HIFU is associated with clinically significant reduction in urinary function after mean follow up of 17.5 months. The reduction of sexual function is probably of less significance in this population. The results are comparable to similar studies done for salvage cryotherapy and seem to show less side effects compared to salvage prostatectomy HRQOL studies."

Registre HIFU

L’outil de gestion globale en ligne pour les utilisateurs HIFU

Objectif
@-Registry est un registre de données en ligne dont le but est d'améliorer la compréhension des résultats de traitement de la prostate par HIFU en compilant ces résultats via des publications et présentations. Pour le praticien, le registre est un outil de gestion des données cliniques et permet l'évaluation statistique des résultats de son propre centre.

Comité scientifique
@-registry est supervisé par un comité scientifique internationalement reconnu, composé d'urologues de 5 pays différents et soutenu par EDAP TMS. Le comité scientifique gère le registre et facilite la parution de présentations, publications, projets.

Débuter sur @-registry

  • Rejoignez le registre en contactant votre délégué EDAP TMS ou John Rewcastle, Directeur médical
  • Le praticien signe un accord d'utilisation
  • Chaque site ou praticien reçoit alors un mot de passe personnalisé
  • L'information Patient anonymisée peut alors être intégrée au registre

L'HIFU est soumis aux législations locales. Contactez-nous pour plus d'informations.