High-intensity focused ultrasound for focal therapy: reality or pitfall?

PURPOSE OF REVIEW: Progress in imaging, fusion software, and ablative modalities has fostered growth of the latest image-guided generation of high-intensity focused ultrasound (HIFU) for focal treatment of prostate cancer. Although early reports are encouraging, important questions remain regarding candidate selection, treatment, and outcomes. We review contemporary considerations for the use of HIFU for focal treatment of primary and radio-recurrent prostate cancer. RECENT FINDINGS: HIFU has been used to treat prostate cancer for over two decades. More recently, stage migration from screening and improvements in pelvic imaging and fusion technology has resulted in wider clinical application of focal HIFU as a first-line treatment for localized prostate cancer. Advanced imaging has also improved targeting for focal salvage therapy of radio-recurrent disease. Proponents point to the minimally invasive nature, limited morbidity profile, and ability to perform retreatments in the future. Critics emphasize positive post-treatment biopsies, nonuniform treatment protocols, and absence of long-term follow-up. Thus, a review of clinical considerations and recently published data is warranted. SUMMARY: Recent advances have strengthened support for the use of focal HIFU. Although HIFU has great potential, it must be applied judiciously, maintaining appropriate oncologic principles in the setting of standardized trials to determine its true clinical value.

High-intensity focused ultrasound (HIFU) for definitive treatment of prostate cancer.

UNLABELLED: What's known on the subject? and What does the study add? Novel therapeutic methods have emerged in recent years as 'focal' treatment alternatives in which cancer foci can be eradicated and greatly reducing the associated side-effects of radical treatment. High-intensity focused ultrasound (HIFU) seems to result in a well fitted technology, which has proven short- to medium-term cancer control, with a low rate of complications comparable with those of established therapies. This is an up-to-date review of the available literature on HIFU as a definitive treatment of prostate cancer. It describes the technique in a comprehensive approach in terms of technical features, procedure, indications, and gives an overview of its historical background; finally, we present the future applications of HIFU and its development trend. OBJECTIVES: • To provide an up-to-date review of the available literature on high-intensity focused ultrasound (HIFU) as a definitive treatment of prostate cancer. • To present the technique in a comprehensive approach, comparing the available devices according to the existing evidence in terms of technical features, procedure, indications, and to give an overview of its historical background; and finally, to discuss future applications of HIFU and its development trend. MATERIALS AND METHODS: • A systematic literature search was conducted using MEDLINE and EMBASE via Ovid databases (January 2000 to December 2011), to identify studies on HIFU for treatment of prostate cancer. • Only English-language and human-based full manuscripts that reported on case series studies with >50 participants, patient characteristics, efficacy and safety data were included. RESULTS: • No randomised controlled trials were identified by the literature search. We identified 31 uncontrolled studies that examined the efficacy of HIFU as primary treatment and two studies that examined the efficacy of HIFU as salvage treatment. • Most treated patients had localised prostate cancer (stage T1-T2); Gleason scores of 2-10 and mean prostate specific antigen (PSA) values of 4.6-12.7 ng/mL. The mean age range of the patients was 64.1-72 years. The mean follow-up ranged from 6.4 to 76.8 months. Negative biopsy rates ranged from 35 to 95%. PSA nadirs ranged from 0.04 to 1.8 ng/mL. The 5-year disease-free survival rates ranged from 61.2 to 95%; 7- and 8-year disease free survival rates ranged from 69 to 84%. • The most common complications associated with the HIFU procedure as the primary treatment included: urinary retention (<1-20%); urinary tract infections (1.8-47.9%); stress or urinary incontinence (<1-34.3%); and erectile dysfunction (20-81.6%). • Recto-urethral fistula was reported in <2% of patients. • Treatment-related morbidity appeared to be reduced by the combination of transurethral resection (TURP) of the prostate and HIFU. CONCLUSIONS: • Novel therapeutic methods have emerged in recent years as 'focal' treatment alternatives, in which cancer foci could be eradicated by greatly reducing the associated side-effects of radical treatment. • HIFU seems to result in short- to medium-term cancer control, with a low rate of complications comparable with those of established therapies. • However, longer-term follow-up studies are needed to evaluate cancer-specific and overall survival. If available promising results on HIFU for definitive treatment of prostate cancer are confirmed in future prospective trials, focal therapy could start to challenge the current standard of care.

Secuestro broncopulmonar fetal con resolución espontánea intraútero / Fetal bronchopulmonary sequestration with spontaneous intrauterine resolution

Presentamos un caso de secuestro broncopulmonar (SBP) sospechado en la ecografía morfológica de la semana 20 de gestación, debido al hallazgo de una imagen triangular ecogénica homogénea en el pulmón izquierdo del feto, que se confirma 2 semanas más tarde al detectar el vaso sistémico que irriga la lesión. Debido a la ausencia de factores de mal pronóstico, se decide mantener una actitud expectante, observándose una disminución progresiva de la lesión hasta su completa desaparición ecográfica en la semana 37 (AU)

We present a case of bronchopulmonary sequestration suspected in the morphological ultrasound at 20 weeks of gestation based on the finding of a homogeneous hyperechoic triangular image in the left lung of the fetus, which was confirmed 2 weeks later with the observation of a blood vessel from the aorta feeding the mass. Due to the absence of poor prognostic factors, an expectant attitude was adopted, with a progressive decrease of the mass until its complete disappearance on ultrasound at 37 weeks (AU)

A biomedical engineering approach to mitigate the errors of prostate biopsy.

The current protocol for detecting and ruling out prostate cancer involves serum PSA testing followed by sampling of the prostate using a transrectal ultrasonography (TRUS)-guided biopsy. Many specialists have discussed how PSA screening has contributed to underdetection of clinically significant prostate cancer, overdiagnosis of clinically insignificant disease and poor risk stratification; however, little consideration has been given to the role of TRUS-guided biopsy in these errors. The performance of TRUS-guided biopsy is constrained by the biomechanical attributes of the sampling strategy, resulting in suboptimal detection efficiency of each core. By using a biomedical engineering approach, a uniform grid sampling strategy could be used to improve the detection efficiency of prostate biopsy. Moreover, the calibration of the sampling can be adjusted by altering the distance between needle deployments. Our model shows that for any given number of needle trajectories, a uniform grid approach will be superior to a divergent, nonuniform strategy for the detection of clinically important disease. This is an important message that should result in a move away from divergent sampling to a uniform grid approach for prostate biopsy.

Ultrasonidos Focalizados de Alta Energía (HIFU) de Rescate en el cáncer de próstata después de Radioterapia / Salvage High energy focalized ultrasound (HIFU) in prostate cancer after radiotherapy

OBJETIVO: Evaluar la eficacia y seguridad de los Ultrasonidos de Alta Intensidad Focalizados (HIFU) como tratamiento de rescate tras radioterapia radical en el cáncer de próstata (CP). MÉTODOS: Se revisa la literatura a través de bases de datos y los artículos publicados que hacen referencia a este tratamiento entre el año 2000 y el 2010. Se han evaluado los resultados oncológicos, así como los efectos adversos, comparando con lo publicado en relación con otras terapias existentes. RESULTADOS: Se evalúan las distintas series publicadas, en las que se incluyen los resultados de los dos dispositivos disponibles en la actualidad, todas ellas con sus resultados iniciales y las que se encuentran en fase de ajuste de dosis. Se puede afirmar de forma general que el mayor problema de todas ellas resulta la morbilidad incial que se reduce según se gana en experiencia con el tratamiento. De forma generalizada, hay que resaltar la importancia de lo cortas que son las series evaluadas, sobre todo en tiempo de seguimiento y en número de pacientes. Asimismo, salvo una revisión sistemática recientemente publicada, no existe ningún estudio prospectivo con ninguno de los dos dispositivos. Todos los resultados de las distintas series publicadas son comparados con la literatura existente en relación a los distintos tratamientos del CP. CONCLUSIONES: A pesar de los resultados publicados, el tratamiento mediante HIFU en la recidiva del cáncer de próstata tras radioterapia es una opción que debe ser considerada. Sobre todo teniendo en cuenta que, en estos pacientes, es importante retrasar el desarrollo de la enfermedad y que no existen otras alternativas que hayan demostrado ser eficaces. Es necesaria una mayor investigación para explorar la utilización de HIFU en el tratamiento cel CP. En cualquier caso, es fundamental la publicación de series prospectivas comparativas y series con mayor número de pacientes y de más largo seguimiento para poder sacar conclusiones definitivas(AU)

OBJECTIVES: To evaluate the efficacy and safety of High Intensity Focused Ultrasound (HIFU) as salvage treatment after radical radiotherapy in prostate cancer (PC). METHODS: We reviewed the literature through databases and published articles that refer to this treatment between 2000 and 2010. We evaluated oncological results and adverse effects, compared with those published in conjunction with other therapies. RESULTS: We evaluated the different series, which include the results of the two devices currently available, all with their initial results and those that are in the process of dose adjustment. Generally, it can be said that the biggest problem of all is that initial morbidity is reduced as the surgeon gains experience with the treatment. We must stress the importance of the short series that are evaluated, especially in follow-up time and number of patients. Also, except for a recently published systematic review, no prospective studies are published. The results from different series are compared with existing literature regarding to other PC treatments. CONCLUSIONS: In spite of published results, the treatment with HIFU for prostate cancer recurrence after radiotherapy is an option that should be considered. Especially considering that, it is important to delay the development of the disease in these patients, and there are no other alternatives that have proven to be effective. Further research is needed to explore the use of HIFU in the treatment of PC. Anyway, it is essential to publish comparative prospective series and series with more patients and longer follow-up to draw definitive conclusions(AU)

¿Cómo contribuye la RMN, el PEC-TC y la ecografía transrectal en el diagnóstico y manejo del cáncer de próstata localizado? / How does endorectal MRI, PET-CT and transrectal ultrasound contributes to diagnostic and management of localized prostate cancer

Analizamos las principales técnicas (ecografía transrectal, resonancia magnética y la tomografia por emisión de positrones) utilizadas en el diagnóstico y manejo de los pacientes diagnosticados de adenocarcinoma de próstata localizado. De la ecografía transrectal analizamos los resultados obtenidos y describimos los últimos avances desarrollados con esta técnica (doppler, power doppler y medios de contraste).De la Resonancia Magnética analizamos los fundamentos, resultados e indicaciones así como las nuevas aplicaciones (difusión, perfusión, espectroscopia y la utilización de nanopartículas paramagnéticas linfotróficas).Y por último, comentaremos el estado actual de la Tomografía por emisión de positrones en el diagnóstico, en la monitorización y en la detección de recurrencias con los distintos radiotrazadores disponibles en el mercado(AU)

We analyze the main imaging techniques (transrectal ultrasound, Magnetic Resonance Imaging and Position Emission Tomography) that are currently used in the diagnosis and management of localised prostate cancer patients. We analyze the results that may be obtained with transrectal US and describe the latest advances in this technique (Doppler, power doppler and contrast media).With Magnetic Resonance Imaging, we describe the underlying principles, results and indications as well as some new applications (diffusion, perfusion, spectroscopy and the use of lymphotrophic nanoparticles).Finally we will describe the current state of positron emission tomography in diagnosis, follow up and recurrence detection using the different radiomarkers that are available(AU)

Tratamiento focal para el cáncer de próstata clinícamente localizado / Focal therapy for clinically localized prostate cancer

La migración del estadío en los tumores de próstata recién diagnosticados, la mejora de las imágenes de la próstata, y los dispositivos capaces de inducir la ablación subtotal de próstata han permitido el estudio formal y la evaluación de la terapia focal para el tumor de próstata de bajo riesgo. Siguen existiendo limitaciones importantes: 1) la necesidad de mayor precisión pre-tratamiento de la ubicación del tumor, extensión y tamaño, 2) determinar métodos apropiados de vigilancia post-tratamiento y definiciones de progresión clínica, 3) la incertidumbre acerca de si la repetición del tratamiento, mediante terapia focal o de toda la glándula es eficaz y seguro. Están en curso ensayos clínicos para proporcionar datos sobre la viabilidad y fiabilidad de estas nuevas terapias, la capacidad de erradicación del tumor, las tasas de tratamiento secundario, y el impacto en la función urinaria y sexual(AU)

The stage migration for newly diagnosed prostate cancer, improvements in prostate imaging, and devices capable of inducing subtotal prostate ablation have allowed for the formal study and evaluation of focal therapy for low-risk prostate cancer. Significant limitations remain: 1) the need for more accurate pre-treatment determination of cancer location, extent, and size, 2) determining appropriate methods of post-treatment surveillance and definitions of clinical progression, 3) the uncertainty whether repeat treatment, by focal or whole-gland therapy, is effective and safe. Clinical trials are ongoing to provide data on the feasibility and reliability of these new therapies, the capability of eradicating cancers, rates of secondary treatment, and impact on urinary and sexual function(AU)

Análisis de imagen asistido por ordenador en ecografía transrectal de próstata / Computer-aided analysis of transrectal ultrasound images of the prostate

Introducción: El método de diagnóstico de elección del cáncer de próstata (CP) es la biopsia transrectal guiada ecográficamente. Sin embargo, es frecuente no objetivar imágenes sospechosas. Los estudios de análisis de imagen pretenden identificar patrones ecográficos propios de una patología aparentemente ocultos. Materiales y método: Registramos digitalmente 288 biopsias transrectales ecoguiadas, de las que se aislaron imágenes estáticas de cada punción-biopsia para su análisis computarizado. Para ello se procedió a la extracción de características de textura mediante «mapeo simple» en escala de gris y «matrices espaciales dependientes del nivel de gris» o «matrices de coaparición», que estudian la relación de cada píxel con sus vecinos. Se desarrolló un sistema de «reconocimiento de formas» con dos métodos de clasificación: «técnica de k-vecinos» y «modelos ocultos de Markov». Finalmente realizamos una simulación del sistema con 4 ecografistas, comparando su capacidad diagnóstica en escala de gris con imágenes procesadas con nuestro sistema en 408 punciones grabadas, no en tiempo real. Resultados: La capacidad diagnóstica (curva ROC) con mapeo simple fue de 59,7 y 61,6% con clasificación mediante k-vecinos y modelos ocultos de Markov, respectivamente. Las matrices de coaparición ofrecieron un área bajo la curva ROC de 60,1 y 60,0%. El experimento virtual se llevó a cabo mediante «mapeo simple» y clasificación con «k-vecinos», otorgando una capacidad diagnóstica en cada urólogo de 63,3, 67,0, 64,3 y 63,7% frente a 61,7, 60,5, 66,2 y 60,7% conseguidas con la imagen original. Conclusiones: La utilización de nuestro método de análisis de imagen tiene una capacidad limitada, aunque estable, en la detección de áreas prostáticas cancerígenas (AU)

Introduction: Prostate cancer is usually diagnosed by transrectal ultrasound (TRUS) biopsy. Nevertheless, suspicious images are frequently not found. Imaging analysis studies aim to identify ultrasound patterns characteristic of apparently hidden conditions. Material and methods: We digitally recorded 288 TRUS ultrasound guided transrectal biopsies and extracted 3 static images from the puncture-biopsy area. The extraction of the texture characteristics were obtained by “simple mapping” on a gray scale and spatial gray level dependence matrices (SGLDM), also known as Haralick‘s co-occurrence matrices, which study the relationship of each pixel and its neighbors. A pattern recognition software system was developed with two different classification methods: nearest neighbor (k-NN) and Markov's hidden models. Finally, a virtual experiment was carried out in which four urologists compared their diagnostic accuracy for prostate cancer with our system in 408 TRUS images, not in real time. Results: The diagnostic capacity (R.O.C. curve) with the simple gray map study was 59.7% with nearest-neighbor classification and 61.6% with Markov's hidden models classification. The co-occurrence matrices showed an area under R.O.C. curve of 60.1% and 60.0% with k-NN and Markov's hidden models classification, respectively. The virtual experiment was conducted with a simple gray map study and k-NN classification. The images processed by our system showed the following diagnostic accuracy: 63.3, 67, 64.3 and 63.7% compared to 61.7, 60.5, 66.2 and 60.7% with the original image. Conclusions: Our pattern recognition system for prostate cancer TRUS images has a limited, yet stable, accuracy (AU)

High intensity focused ultrasound (HIFU) for prostate cancer: current clinical status, outcomes and future perspectives.

Two devices are currently available for the treatment of prostate cancer with HIFU: Sonablate® and Ablatherm®. The outcomes achieved for primary-care patient are very promissing with mid- and long-term progression-free survival rates around 70%, negative postoperative prostate biopsies almost 85%, and an excellent morbidity profile. Moreover, HIFU has a considerable potential for local recurrence after radiation failure. Recently, some early experiences on focal therapy suggest that HIFU could be an excellent option for highly selected patient.

[Transrectal high-intensity focused ultrasound for local treatment of prostate cancer. 2009 Update]. / Hoch intensiver fokussierter transrektaler Ultraschall (rHIFU) zur lokalen Therapie des Prostatakarzinoms. Update 2009.

Pulsed robotic high-intensity focused ultrasound (rHIFU) is an interesting therapeutic option mainly due to its noninvasive character. In urologic oncology, rHIFU is used for the transrectal therapy of prostate cancer. While percutaneous therapy of renal cancer using rHIFU is still being tested in experimental studies, transrectal therapy with rHIFU for prostate cancer is already established in more than 230 urologic departments worldwide. The results of prostate cancer therapy with rHIFU are mainly based on different clinical studies. In 2007 a clinical study comparing rHIFU and cryotherapy for the treatment of prostate cancer was initiated in the USA in order to gain clinical approval by the FDA. The most recent publications concluded that the use of rHIFU is an effective standard treatment for prostate cancer with a broad range of indications in all tumor stages: (1) in the primary treatment of local prostate cancer, (2) in patients with local recurrence after failure of any primary treatment, and (3) as an adjuvant therapy in the palliation of systemic prostate cancer.

Focal therapy for prostate cancer: revolution or evolution?

The face of prostate cancer has been dramatically changed since the late 1980s when PSA was introduced as a clinical screening tool. More men are diagnosed with small foci of cancers instead of the advanced disease evident prior to PSA screening. Treatment options for these smaller tumors consist of expectant management, radiation therapy (brachytherapy and external beam radiotherapy) and surgery (cryosurgical ablation and radical prostatectomy). In the highly select patient, cancer specific survival employing any of these treatment options is excellent, however morbidity from these interventions are significant. Thus, the idea of treating only the cancer within the prostate and sparing the non-cancerous tissue in the prostate is quite appealing, yet controversial. Moving forward if we are to embrace the focal treatment of prostate cancer we must: be able to accurately identify index lesions within the prostate, image cancers within the prostate and methodically study the litany of focal therapeutic options available.

Current status of HIFU and cryotherapy in prostate cancer--a review.

OBJECTIVES: To evaluate the current status of high-intensity focused ultrasound (HIFU) and cryosurgery as the primary treatment option in patients with prostate cancer. METHOD: A MedLine search using specified search terms was done on February 28, 2005. This search rendered 150 papers related to HIFU and 566 papers related to cryosurgery. Very few of these papers presented original outcome data and are included in the present review. RESULTS: No controlled trial was available for analysis, and no survival data were presented. No validated biochemical, surrogate end point was available for any of the two therapies. HIFU showed progression-free survival (based on prostate-specific antigen+/-biopsy data) of 63-87% (projected 3- to 5-yr data), but median follow-up in the studies ranged from 12-24 mo. Negative postoperative biopsies was seen in 82-94% of patients. Complications have been reduced by the combination of transurethral resection of the prostate and HIFU. Cryosurgery showed a progression-free survival of 36-92% (projected 1-7 yr data), depending on risk groups and definition of failure. Negative biopsies were seen in 72-87%, but no biopsy data were available for the currently used third-generation cryotherapy machines. Complications seem to be lower with the third-generation machines. CONCLUSIONS: None of the evaluated therapies has enough data available to support their use as an alternative to established therapies (surgery, radiation) for localised prostate cancer. Until further data become available, the use of both treatments should be restricted to patients unfit for established therapies who still have the need for local therapy.

High intensity focused ultrasound: surgery of the future?

For 50 years, high intensity focused ultrasound (HIFU) has been a subject of interest for medical research. HIFU causes selective tissue necrosis in a very well defined volume, at a variable distance from the transducer, through heating or cavitation. Over the past decade, the use of HIFU has been investigated in many clinical settings. This literature review aims to summarize recent advances made in the field. A Medline-based literature search (1965-2002) was conducted using the keywords "HIFU" and "high intensity focused ultrasound". Additional literature was obtained from original papers and published meeting abstracts. The most abundant clinical trial data comes from studies investigating its use in the treatment of prostatic disease, although early research looked at applications in neurosurgery. More recently horizons have been broadened, and the potential of HIFU as a non-invasive surgical tool has been demonstrated in many settings including the treatment of tumours of the liver, kidney, breast, bone, uterus and pancreas, as well as conduction defects in the heart, for surgical haemostasis, and the relief of chronic pain of malignant origin. Further clinical evaluation will follow, but recent technological development suggests that HIFU is likely to play a significant role in future surgical practice.