Salvage High-Intensity Focused Ultrasound for Local Recurrence in the Prostatic Bed after Prostatectomy and Adjuvant or Salvage Radiotherapy: Preliminary Results.

PURPOSE: We sought to report the preliminary results of salvage high-intensity focused ultrasound for locally recurrent prostate cancer in the prostatic bed after radical prostatectomy and adjuvant or salvage radiotherapy. MATERIALS AND METHODS: We retrospectively analyzed a single-center cohort of men treated with salvage high-intensity focused ultrasound for locally recurrent prostate cancer after radical prostatectomy and adjuvant or salvage radiotherapy. All patients had a combination of choline positron emission tomography, multiparametric magnetic resonance imaging, and transrectal biopsies to confirm the local recurrence. Treatment failure was defined as persistent or recurrent prostate cancer in the prostatic bed and/or metastasis and/or introduction of systemic treatment. Progression was defined as metastasis and/or introduction of systemic treatment. Complications (Clavien-Dindo classification) and continence (Ingelman-Sundberg score) were evaluated. Kaplan-Meier analysis estimated oncological outcomes. RESULTS: Between July 2009 and November 2018, 22 patients were included; the median followup was 2.32 years. At 3 years, treatment failure-free survival rate was estimated to be 49.7% and progression-free survival rate 60.4%. Prostate specific antigen nadir ≤0.2 ng/ml was reached in 50% of the patients. A nadir of ≤0.2 ng/ml was significantly associated with better treatment failure-free and progression-free survival probabilities (p=0.003 and p=0.037, respectively). Grade III complications occurred in 6 patients (27.3%). Onset of grade II-III incontinence was significantly more frequent in cases of perianastomotic (36.4%) compared to retrovesical recurrence (0%; p=0.027). CONCLUSIONS: Salvage high-intensity focused ultrasound for locally recurrent prostate cancer after radical prostatectomy and salvage radiotherapy showed encouraging oncological results despite significant morbidity. The perianastomotic recurrence was linked to a higher risk of incontinence.

Salvage high-intensity focused ultrasound for locally recurrent prostate cancer after low-dose-rate brachytherapy: oncological and functional outcomes.

OBJECTIVES: To evaluate the oncological and functional outcomes of salvage high-intensity focused ultrasound (S-HIFU) for locally recurrent prostate cancer after low-dose-rate (LDR) brachytherapy. PATIENTS AND METHODS: Clinical phase II studies (2003-2015) included 50 consecutive patients with post-brachytherapy local recurrence treated by S-HIFU. S-HIFU was performed with post-external beam radiotherapy (EBRT) parameters and, since 2008, with specific post-brachytherapy parameters. Treatments were whole-gland ablation and, since 2009, hemi-ablation in cases of unilateral prostate cancer. The primary objective was to assess oncological outcomes: treatment failure-free survival, progression-free survival (PFS), overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS) rates. The secondary objective was to evaluate adverse events, continence, and erectile function. Kaplan-Meier analysis estimated oncological outcomes. RESULTS: In all, 13 patients were treated with post-EBRT parameters, 37 with post-brachytherapy parameters, 35 with whole-gland treatment, and 15 with hemi-ablation. The median follow-up was 4.6 years. After S-HIFU, the median prostate-specific antigen level was 0.3 ng/mL. At 6 years, treatment failure-free survival, PFS, OS, CSS, and MFS rates were 41%, 45%, 93%, 98%, and 80%, respectively. Post-brachytherapy compared with post-EBRT parameters reduced Grade 2-3 incontinence (34% vs 62%, P = 0.015). Incontinence, bladder outlet obstruction and Grade ≥III complications were significantly reduced with hemi-ablation compared with whole-gland treatment (14% vs 54%, P < 0.001; 13% vs 46%, P = 0.03; 13% vs 63%, P = 0.001; respectively). Before S-HIFU, 25 patients had a five-item version of the International Index of Erectile Function score of ≥17, which was maintained in 48% at 12 months. CONCLUSION: S-HIFU for locally recurrent prostate cancer after LDR brachytherapy is associated with favourable survival rates at a price of significant morbidity. Dedicated post-brachytherapy parameters and hemi-ablation improve the safety of the treatment.

Salvage high-intensity focused ultrasound (HIFU) for locally recurrent prostate cancer after failed radiation therapy: Multi-institutional analysis of 418 patients.

OBJECTIVE: To report the oncological outcome of salvage high-intensity focused ultrasound (S-HIFU) for locally recurrent prostate cancer after external beam radiotherapy (EBRT) from a multicentre database. PATIENTS AND METHODS: This retrospective study comprises patients from nine centres with local recurrent disease after EBRT treated with S-HIFU from 1995 to 2009. The biochemical failure-free survival (bFFS) rate was based on the 'Phoenix' definition (PSA nadir + 2 ng/mL). Secondary endpoints included progression to metastasis and cancer-specific death. Kaplan-Meier analysis was performed examining overall (OS), cancer-specific (CSS) and metastasis-free survival (MFS). Adverse events and quality of life status are reported. RESULTS: In all, 418 patients with a mean (SD) follow-up of 3.5 (2.5) years were included. The mean (SD) age was 68.6 (5.8) years and the PSA level before S-HIFU was 6.8 (7.8) ng/mL. The median PSA nadir after S-HIFU was 0.19 ng/mL. The OS, CSS and MFS rates at 7 years were 72%, 82% and 81%, respectively. At 5 years the bFFS rate was 58%, 51% and 36% for pre-EBRT low-, intermediate- and high-risk patients, respectively. The 5-year bFFS rate was 67%, 42% and 22% for pre-S-HIFU PSA level ≤4, 4-10 and ≥10 ng/mL, respectively. Complication rates decreased after the introduction of specific post-RT parameters: incontinence (grade II or III) from 32% to 19% (P = 0.002); bladder outlet obstruction or stenosis from 30% to 15% (P = 0.003); recto-urethral fistula decreased from 9% to 0.6% (P < 0.001). Study limitations include being a retrospective analysis from a registry with no control group. CONCLUSION: S-HIFU for locally recurrent prostate cancer after failed EBRT is associated with 7-year CSS and MFS rates of >80% at a price of significant morbidity. S-HIFU should be initiated early following EBRT failure.

Can pre- and postoperative magnetic resonance imaging predict recurrence-free survival after whole-gland high-intensity focused ablation for prostate cancer?

OBJECTIVES: Our aim was to assess whether magnetic resonance imaging (MRI) features predict recurrence-free survival (RFS) after prostate cancer high-intensity focused ultrasound (HIFU) ablation. METHODS: We retrospectively selected 81 patients who underwent (i) whole-gland HIFU ablation between 2007 and 2011 as first-line therapy or salvage treatment after radiotherapy or brachytherapy, and (ii) pre- and postoperative MRI. On preoperative imaging, two senior (R1, R2) and one junior (R3) readers assessed the number of sectors invaded by the lesion with the highest Likert score (dominant lesion) using a 27-sector diagram. On postoperative imaging, readers assessed destruction of the dominant lesion using a three-level score. Multivariate analysis included the number of sectors invaded by the dominant lesion, its Likert and destruction scores, the pre-HIFU prostate-specific antigen (PSA) level, Gleason score, and the clinical setting (primary/salvage). RESULTS: The most significant predictor was the number of prostate sectors invaded by the dominant lesion for R2 and R3 (p≤0.001) and the destruction score of the dominant lesion for R1 (p = 0.011). The pre-HIFU PSA level was an independent predictor for R2 (p = 0.014), but with only marginal significance for R1 (p = 0.059) and R3 (p = 0.053). CONCLUSION: The dominant lesion's size and destruction assessed by MRI provide independent prognostic information compared with usual predictors. KEY POINTS: • The size of the MR-dominant lesion significantly influences post-HIFU recurrence-free survival. • The destruction score of the MR-dominant lesion predicts post-HIFU recurrence-free survival. • Patients with a completely devascularized MR-dominant lesion show better recurrence-free survival • Pre- and post-HIFU MRI provide prognostic information independent of usual predictors.

Prostate Focused Ultrasound Therapy.

The tremendous progress in engineering and computing power coupled with ultrasound transducer technology and imaging modalities over the past 20 years have encouraged a revival of clinical interest in ultrasound therapy, mainly in High-Intensity Focused Ultrasound (HIFU). So far, the most extensive results from HIFU obtained in urology involve transrectal prostate ablation, which appears to be an effective therapeutic alternative for patients with malignant prostate tumors. Prostate cancer (PCa) is one of the most frequently diagnosed cancers in men. Several treatment options with different therapeutic approaches exist, including HIFU for localized PCa that has been in use for over 15 years. Since the early 2000s, two systems have been marketed for this application, and other devices are currently in clinical trials. HIFU treatment can be used either alone or in combination with (before- or after-) external beam radiotherapy (EBRT) (before or after HIFU) and can be repeated multiple times. HIFU treatment is performed under real-time monitoring with ultrasound or guided by MRI. Two indications are validated today: Primary care treatment and EBRT failure. The results of HIFU for primary care treatment are similar to standard conformal EBRT, even though no randomized comparative studies have been performed and no 10-year follow up data is yet available for HIFU. Salvage HIFU after EBRT failure is increasing with oncological outcomes, similar to those achieved with surgery but with the advantage of fewer adverse effects. HIFU is an evolving technology perfectly adapted for focal treatment. Thus, HIFU focal therapy is another pathway that must be explored when considering the accuracy and reliability for PCa mapping techniques. HIFU would be particularly suited for such a therapy since it is clear that HIFU outcomes and toxicity are relative to the volume of prostate treated.

How accurate is multiparametric MR imaging in evaluation of prostate cancer volume?

PURPOSE: To assess the factors influencing multiparametric (MP) magnetic resonance (MR) imaging accuracy in estimating prostate cancer histologic volume (Vh). MATERIALS AND METHODS: A prospective database of 202 patients who underwent MP MR imaging before radical prostatectomy was retrospectively used. Institutional review board approval and informed consent were obtained. Two independent radiologists delineated areas suspicious for cancer on images (T2-weighted, diffusion-weighted, dynamic contrast material-enhanced [DCE] pulse sequences) and scored their degree of suspicion of malignancy by using a five-level Likert score. One pathologist delineated cancers on whole-mount prostatectomy sections and calculated their volume by using digitized planimetry. Volumes of MR true-positive lesions were measured on T2-weighted images (VT2), on ADC maps (VADC), and on DCE images [VDCE]). VT2, VADC, VDCE and the greatest volume determined on images from any of the individual MR pulse sequences (Vmax) were compared with Vh (Bland-Altman analysis). Factors influencing MP MR imaging accuracy, or A, calculated as A = Vmax/Vh, were evaluated using generalized linear mixed models. RESULTS: For both readers, Vh was significantly underestimated with VT2 (P < .0001, both), VADC (P < .0001, both), and VDCE (P = .02 and P = .003, readers 1 and 2, respectively), but not with Vmax (P = .13 and P = .21, readers 1 and 2, respectively). Mean, 25th percentile, and 75th percentile, respectively, for Vmax accuracy were 0.92, 0.54, and 1.85 for reader 1 and 0.95, 0.57, and 1.77 for reader 2. At generalized linear mixed (multivariate) analysis, tumor Likert score (P < .0001), Gleason score (P = .009), and Vh (P < .0001) significantly influenced Vmax accuracy (both readers). This accuracy was good in tumors with a Gleason score of 7 or higher or a Likert score of 5, with a tendency toward underestimation of Vh; accuracy was poor in small (<0.5 cc) or low-grade (Gleason score ≤6) tumors, with a tendency toward overestimation of Vh. CONCLUSION: Vh can be estimated by using Vmax in aggressive tumors or in tumors with high Likert scores.

Complications after artificial urinary sphincter implantation in patients with or without prior radiotherapy.

OBJECTIVE: To compare complications after implantation of an artificial urinary sphincter (AUS) in patients with or without prior radiotherapy (RT). PATIENTS AND METHODS: Between January 2000 and December 2011, 160 patients underwent AMS 800 AUS implantation in our institution. We excluded neurological and traumatic causes, implantation on ileal conduit diversion, penoscrotal urethral cuff position and those lost to follow-up. In all, 122 patients were included in the study, 61 with prior RT and 61 without prior RT. All patients underwent the same surgical technique by two different surgeons. All AUS were implanted with a bulbar urethral cuff position. The mean (range) follow-up was 37.25 (1-126) months. RESULTS: In the patients without prior RT and those with prior RT, revision rates were 32.8% vs 29.5%, respectively (P = 0.59). The median time to first revision was 11.7 months. Early complications were similar in the two groups (4.9% vs 6.5%, P = 1). Erosion rates were not significantly different (4.9% vs 13.1%, P = 0.13). However, infection and explantation were more prevalent in patients with prior RT [two (3.2%) vs 10 (16.3%), P = 0.018 and three (4.9%) vs 12 (19.6%), P = 0.016, respectively]. Finally, continence rates were not significantly different [75.4% (without prior RT) vs 63.9% (with prior RT), P = 0.23]. CONCLUSION: AUS is the 'gold standard' treatment of male urinary incontinence after re-education failure in patients with or without prior RT. Our experience showed similar functional outcomes in both groups but a higher rate of major complications in the group with prior RT.

Hemi salvage high-intensity focused ultrasound (HIFU) in unilateral radiorecurrent prostate cancer: a prospective two-centre study.

OBJECTIVE: To report the oncological and functional outcomes of hemi salvage high-intensity focused ultrasound (HSH) in patients with unilateral radiorecurrent prostate cancer. PATIENTS AND METHODS: Between 2009 and 2012, 48 patients were prospectively enrolled in two European centres. Inclusion criteria were biochemical recurrence (BCR) after primary radiotherapy (RT), positive magnetic resonance imaging and ≥1 positive biopsy in only one lobe. BCR was defined using Phoenix criteria (a rise by ≥2 ng/mL above the nadir prostate specific antigen [PSA] level). The following schemes and criteria for functional outcomes were used: Ingelman-Sundberg score using International Continence Society (ICS) questionnaire (A and B), International prostate symptom score (IPSS), International Index of Erectile Function-5 (IIEF-5) points, the European Organisation for the Research and Treatment of Cancer (EORTC) quality of life questionnaires (QLQ C-30). HSH was performed under spinal or general anaesthesia using the Ablatherm® Integrated Imaging device. Patients with obstructive voiding symptoms at the time of treatment underwent an endoscopic bladder neck resection or incision during the same anaesthesia to prevent the risk of postoperative obstruction. RESULTS: After HSH the mean (sd) PSA nadir was 0.69 (0.83) ng/mL at a median (interquartile range) follow-up of 16.3 (10.5-24.5) months. Disease progression occurred in 16/48 (33%). Of these, four had local recurrence in the untreated lobe and four bilaterally, six developed metastases, and two had rising PSA levels without local recurrence or radiological confirmed metastasis. Progression-free survival rates at 12, 18, and 24 months were 83%, 64%, and 52%. Severe incontinence occurred in four of the 48 patients (8%), eight (17%) required one pad a day, and 36/48 (75%) were pad-free. The ICS questionnaire showed a mean (sd) deterioration from 0.7 (2.0) to 2.3 (4.5) for scores A and 0.6 (1.4) to 1.6 (3.0) for B. The mean (sd) IPSS and erectile function (IIEF-5) scores decreased from a mean (sd) of 7.01 (5.6) to 8.6 (5.1) and from 11.2 (8.6) to 7.0 (5.8), respectively. The mean (sd) EORTC QLC-30 scores before and after HSH were 35.7 (8.6) vs 36.8 (8.6). CONCLUSION: HSH is a feasible therapeutic option in patients with unilateral radiorecurrent prostate cancer, which offers limited urinary and rectal morbidity, and preserves health-related quality of life.

High-intensity focused ultrasound as focal therapy of prostate cancer.

PURPOSE OF REVIEW: High-intensity focused ultrasound (HIFU) has been widely used for whole gland ablation with large series. HIFU induces immediate and irreversible coagulative necrosis with sharply delineated boundaries making HIFU an attractive treatment option for focal therapy of localized prostate. The treatment can be accurately targeted to a portion of the prostate gland. Unlike radiation, there is no lifetime dose limit, allowing HIFU to be repeated if necessary. Additional radical therapy can be performed involving radical surgery, external beam radiation therapy and cryotherapy. Moreover, HIFU is a minimally invasive therapy that can be performed under spinal anesthesia on an outpatient basis. RECENT FINDINGS: Focal therapy is a new treatment modality for localized prostate cancer. Different energy can be employed to achieve focal therapy including HIFU. With a transrectal treatment, HIFU is one of the less invasive focal treatments. A systematic review of the literature has been performed to highlight the results of focal HIFU. SUMMARY: The first published results of focal HIFU are promising. The patient's quality of life and potency are well preserved with good early oncological results.

Is it possible to model the risk of malignancy of focal abnormalities found at prostate multiparametric MRI?

OBJECTIVE: To evaluate whether focal abnormalities (FAs) depicted by prostate MRI could be characterised using simple semiological features. METHODS: 134 patients who underwent T2-weighted, diffusion-weighted and dynamic contrast-enhanced MRI at 1.5 T before prostate biopsy were prospectively included. FAs visible at MRI were characterised by their shape, the degree of signal abnormality (0 = normal to 3 = markedly abnormal) on individual MR sequences, and a subjective score (SS(1) = probably benign to SS(3) = probably malignant). FAs were then biopsied under US guidance. RESULTS: 56/233 FAs were positive at biopsy. The subjective score significantly predicted biopsy results (P < 0.01). As compared to SS(1) FAs, the odds ratios (OR) of malignancy of SS(2) and SS(3) FAs were 9.9 (1.8-55.9) and 163.8 (11.5-2331). Unlike FAs' shape, a simple combination of MR signal abnormalities (into "low-risk", "intermediate" and "high-risk" groups) significantly predicted biopsy results (P < 0.008). As compared to "low risk" FAs, the OR of malignancy of "intermediate" and "high-risk" FAs were 4.5 (1.1-18.4) and 52.7 (6.8-407) in the overall population and 5.4 (1.1-27.2) and 118.2 (6.1-2301) in PZ. CONCLUSIONS: A simple combination of signal abnormalities of individual MR sequences can significantly stratify the risk of malignancy of FAs, holding promise of a more standardised interpretation of MRI by readers with varying experience. KEY POINTS: • Using multiparameter(mp)-MRI, experienced uroradiologists can stratify the malignancy risk of prostatic lesions • The shape of prostatic focal abnormalities in the peripheral zone does not help predicting malignancy. • A simple combination of findings at mp-MRI can help less-experienced radiologists.

Prostate cancer ablation with transrectal high-intensity focused ultrasound: assessment of tissue destruction with contrast-enhanced US.

PURPOSE: To assess contrast material-enhanced ultrasonographic (US) findings seen after high-intensity focused ultrasound (HIFU) ablation of prostate cancer and correlate the US findings with post-HIFU biopsy findings. MATERIALS AND METHODS: The study was ethics committee approved. Written informed consent was obtained from all patients. Twenty-eight patients referred for HIFU prostate cancer ablation underwent contrast-enhanced prostate US before treatment, gadolinium-enhanced magnetic resonance (MR) imaging and repeat contrast-enhanced US 1-3 days after treatment, and contrast-enhanced US-guided biopsy 30-45 days after treatment. The contrast-enhanced US enhancement patterns of the biopsy sites--assigned a score of S0 for no enhancement, S1 for mild and/or patchy enhancement, or S2 for marked enhancement--were compared with corresponding biopsy findings, which were assigned a score of B0 for necrosis and/or fibrosis without viable prostate gland tissue, B1 for vascularized tissue without viable gland tissue, or B2 for viable gland tissue (benign or malignant). Then, six additional patients underwent contrast-enhanced prostate US 15-30 minutes and 1 day after HIFU ablation, and the results of these two US examinations were compared. RESULTS: Contrast-enhanced US performed on days 1-3 and days 30-45 after HIFU ablation depicted a large devascularized zone with peripheral enhancing areas that were localized anteriorly in all 28 patients, posteriorly in nine, laterally in five, and at the apex in 20 patients. MR findings were concordant. At biopsy, viable gland tissue was found at nine (6.2%) of 146 S0 sites, 10 (34%) of 29 S1 sites, and 44 (60%) of 73 S2 sites. The odds ratios for finding viable tissue (score B1 or B2) at S1 and S2 sites as opposed to S0 sites were 21 (95% confidence interval [CI]: 6, 71) and 73 (95% CI: 22, 243), respectively (P < .0001). Contrast-enhanced US performed 15-30 minutes and 1 day after treatment in the six additional patients had similar findings. CONCLUSION: Contrast-enhanced US is a promising tool for distinguishing between ablated (devascularized) and viable (enhancing) tissue immediately after HIFU treatment.

Location of residual cancer after transrectal high-intensity focused ultrasound ablation for clinically localized prostate cancer.

UNLABELLED: What's known on the subject ? and What does the study add? Transrectal High-Intensity Focused Ultrasound (HIFU) ablation has been used as a minimally invasive treatment for localized prostate cancer for 15 years. Five-year disease-free survival rates of 66-78% have been reported, challenging the results of external-beam radiation therapy. Usually, a 6-mm safety margin is used in the apex to preserve the urinary sphincter and potency. The influence of this 6-mm margin on the results of the treatment has never been assessed. This retrospective study of a cohort of 99 patients who underwent systematic biopsy 3-6 months after HIFU ablation for prostate cancer (with a 6-mm safety margin in the apex) shows that post-HIFU residual cancer is found more frequently in the apex. Therefore, new strategies improving the prostate destruction at the apex while preserving the urinary continence need to be found. OBJECTIVE: • To evaluate whether the location (apex/midgland/base) of prostate cancer influences the risk of incomplete transrectal high-intensity focused ultrasonography (HIFU) ablation. PATIENTS AND METHODS: • We retrospectively studied 99 patients who underwent prostate cancer HIFU ablation (Ablatherm; EDAP, Vaulx-en-Velin, France) with a 6-mm safety margin at the apex, and had systematic biopsies 3-6 months after treatment. • Locations of positive pre- and post-HIFU sextants were compared. • The present study included two analyses. First, sextants negative before and positive after treatment were recoded as positive/positive, hypothesizing that cancer had been missed at pretreatment biopsy. Second, patients with such sextants were excluded. RESULTS: • Pre-HIFU biopsies found cancer in all patients and in 215/594 sextants (36.2%); 55 (25.6%) positive sextants were in the apex, 86 (40%) in the midgland and 74 (34.4%) in the base. • After treatment, residual cancer was found in 36 patients (36.4%) and 50 sextants (8.4%); 30 (60%) positive sextants were in the apex, 12 (24%) in the midgland and eight (16%) in the base. • Both statistical analyses found that the locations of the positive sextants before and after HIFU ablation were significantly different (P < 0.001), with a higher proportion of positive apical sextants after treatment. • At the first analysis, the mean (95% confidence interval) probability for a sextant to remain positive after HIFU ablation was 8.8% (3.5-20.3%) in the base, 12.7% (5.8-25.9%) in the midgland and 41.7% (27.2-57.89%) in the apex. • At the second analysis, these same probabilities were 5.9% (1.9-17%), 9.9% (3.9-23.2%) and 27.3% (13.7-47%), respectively. CONCLUSION: • When a 6-mm apical safety margin is used, residual cancer after HIFU ablation is found significantly more frequently in the apex.

Prostate cancer transrectal HIFU ablation: detection of local recurrences using T2-weighted and dynamic contrast-enhanced MRI.

The objective was to evaluate T2-weighted (T2w) and dynamic contrast-enhanced (DCE) MRI in detecting local cancer recurrences after prostate high-intensity focused ultrasound (HIFU) ablation. Fifty-nine patients with biochemical recurrence after prostate HIFU ablation underwent T2-weighted and DCE MRI before transrectal biopsy. For each patient, biopsies were performed by two operators: operator 1 (blinded to MR results) performed random and colour Doppler-guided biopsies ("routine biopsies"); operator 2 obtained up to three cores per suspicious lesion on MRI ("targeted biopsies"). Seventy-seven suspicious lesions were detected on DCE images (n = 52), T2w images (n = 2) or both (n = 23). Forty patients and 41 MR lesions were positive at biopsy. Of the 36 remaining MR lesions, 20 contained viable benign glands. Targeted biopsy detected more cancers than routine biopsy (36 versus 27 patients, p = 0.0523). The mean percentages of positive cores per patient and of tumour invasion of the cores were significantly higher for targeted biopsies (p < 0.0001). The odds ratios of the probability of finding viable cancer and viable prostate tissue (benign or malignant) at targeted versus routine biopsy were respectively 3.35 (95% CI 3.05-3.64) and 1.38 (95% CI 1.13-1.63). MRI combining T2-weighted and DCE images is a promising method for guiding post-HIFU biopsy towards areas containing recurrent cancer and viable prostate tissue.

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.

Evaluation of T2-weighted and dynamic contrast-enhanced MRI in localizing prostate cancer before repeat biopsy.

We assessed the accuracy of T2-weighted (T2w) and dynamic contrast-enhanced (DCE) 1.5-T magnetic resonance imaging (MRI) in localizing prostate cancer before transrectal ultrasound-guided repeat biopsy. Ninety-three patients with abnormal PSA level and negative prostate biopsy underwent T2w and DCE prostate MRI using pelvic coil before repeat biopsy. T2w and DCE images were interpreted using visual criteria only. MR results were correlated with repeat biopsy findings in ten prostate sectors. Repeat biopsy found prostate cancer in 23 patients (24.7%) and 44 sectors (6.6%). At per patient analysis, the sensitivity, specificity, positive and negative predictive values were 47.8%, 44.3%, 20.4% and 79.5% for T2w imaging and 82.6%, 20%, 24.4% and 93.3% for DCE imaging. When all suspicious areas (on T2w or DCE imaging) were taken into account, a sensitivity of 82.6% and a negative predictive value of 100% could be achieved. At per sector analysis, DCE imaging was significantly less specific (83.5% vs. 89.7%, p < 0.002) than T2w imaging; it was more sensitive (52.4% vs. 32.1%), but the difference was hardly significant (p = 0.09). T2w and DCE MRI using pelvic coil and visual diagnostic criteria can guide prostate repeat biopsy, with a good sensitivity and NPV.

Current status of high-intensity focused ultrasound for prostate cancer: technology, clinical outcomes, and future.

Based on a review of recently published articles, we evaluated the current status of high-intensity focused ultrasound (HIFU) as a primary treatment option for localized prostate cancer and as a salvage therapy when radiation has failed. With mid- and long-term progression-free survival rates around 70%, negative postoperative prostate biopsies almost 90%, and an excellent morbidity profile, primary HIFU appears to be a valid alternative to active surveillance protocols in low-risk patients and standard therapies in patients with life expectancies of 10 or fewer years. Moreover, HIFU has a considerable potential for local-only recurrence after radiation failure. HIFU is a recent technology, and many improvements will undoubtedly expand its future indications and use for the management of prostate cancer.

Transrectal high-intensity focused ultrasound ablation of prostate cancer: effective treatment requiring accurate imaging.

Transrectal HIFU ablation has become a reasonable option for the treatment of localized prostate cancer in non-surgical patients, with 5-year disease-free survival similar to that of radiation therapy. It is also a promising salvage therapy of local recurrence after radiation therapy. These favourable results are partly due to recent improvements in prostate cancer imaging. However, further improvements are needed in patient selection, pre-operative localization of the tumor foci, assessment of the volume treated and early detection of recurrence. A better knowledge of the factors influencing the HIFU-induced tissue destruction and a better pre-operative assessment of them by imaging techniques should improve treatment outcome. Whereas prostate HIFU ablation is currently performed under transrectal ultrasound guidance, MR guidance with real-time operative monitoring of temperature will be available in the near future. If this technique will give better targeting and more uniform tissue destruction, its cost-effectiveness will have to be carefully evaluated. Finally, a recently reported synergistic effect between HIFU ablation and chemotherapy opens possibilities for treatment in high-risk or clinically advanced tumors.

Focal High Intensity Focused Ultrasound of Unilateral Localized Prostate Cancer: A Prospective Multicentric Hemiablation Study of 111 Patients.

BACKGROUND: Up to a third of patients with localized prostate cancer have unilateral disease that may be suitable for partial treatment with hemiablation. OBJECTIVE: To evaluate the ability of high intensity focused ultrasound (HIFU) to achieve local control of the tumor in patients with unilateral localized prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: The French Urological Association initiated a prospective IDEAL multi-institutional study (2009-2015), to evaluate HIFU-hemiablation as a primary treatment. INTERVENTION: Multiparametric magnetic resonance imaging and biopsy were used for unilateral cancer diagnosis and control, and HIFU-hemiablation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary: absence of clinically significant cancer (CSC) on control biopsy at 1 yr (CSC: Gleason score ≥ 7 or cancer core length>3mm regardless of grade or > 2 positive cores). Secondary: presence of any cancer on biopsy, biochemical response, radical treatment free survival, adverse events, continence (no pad), erectile function (International Index of Erectile Function-5 ≥ 16), and quality of life (European Organization for Research and Treatment of Cancer QLQ-C28) questionnaires. RESULTS AND LIMITATIONS: One hundred and eleven patients were treated (mean age: 64.8 yr [standard deviation 6.2]; mean prostate-specific antigen: 6.2 ng/ml [standard deviation 2.6]; 68% low risk, 32% intermediate risk). Of the 101 patients with control biopsy, 96 (95%) and 94 (93%) had no CSC in the treated and contralateral lobes, respectively. Mean prostate-specific antigen at 2 yr was 2.3 ng/ml (standard deviation 1.7). The radical treatment-free survival rate at 2 years was 89% (radical treatments: six radical prostatectomies, three radiotherapies, and two HIFU). Adverse events were Grade 3 in 13%. At 12 mo continence and erectile functions were preserved in 97% and 78%. No significant decrease in quality of life score was observed at 12 mo. One limitation is the number of low-risk patients included in this study. CONCLUSIONS: At 1 yr, HIFU-hemiablation was efficient with 95% absence of clinically significant cancer associated with low morbidity and preservation of quality of life. Radical treatment-free survival rate was 89% at 2 yr. PATIENT SUMMARY: This report shows that high intensity focused ultrasound half-gland treatment of unilateral prostate cancer provides promising results with high cancer control and low morbidity.

Accuracy of Elastic Fusion of Prostate Magnetic Resonance and Transrectal Ultrasound Images under Routine Conditions: A Prospective Multi-Operator Study.

PURPOSE: To evaluate in unselected patients imaged under routine conditions the co-registration accuracy of elastic fusion between magnetic resonance (MR) and ultrasound (US) images obtained by the Koelis Urostation™. MATERIALS AND METHODS: We prospectively included 15 consecutive patients referred for placement of intraprostatic fiducials before radiotherapy and who gave written informed consent by signing the Institutional Review Board-approved forms. Three fiducials were placed in the prostate under US guidance in standardized positions (right apex, left mid-gland, right base) using the Koelis Urostation™. Patients then underwent prostate MR imaging. Four operators outlined the prostate on MR and US images and an elastic fusion was retrospectively performed. Fiducials were used to measure the overall target registration error (TRE3D), the error along the antero-posterior (TREAP), right-left (TRERL) and head-feet (TREHF) directions, and within the plane orthogonal to the virtual biopsy track (TRE2D). RESULTS: Median TRE3D and TRE2D were 3.8-5.6 mm, and 2.5-3.6 mm, respectively. TRE3D was significantly influenced by the operator (p = 0.013), fiducial location (p = 0.001) and 3D axis orientation (p<0.0001). The worst results were obtained by the least experienced operator. TRE3D was smaller in mid-gland and base than in apex (average difference: -1.21 mm (95% confidence interval (95%CI): -2.03; -0.4) and -1.56 mm (95%CI: -2.44; -0.69) respectively). TREAP and TREHF were larger than TRERL (average difference: +1.29 mm (95%CI: +0.87; +1.71) and +0.59 mm (95%CI: +0.1; +0.95) respectively). CONCLUSIONS: Registration error values were reasonable for clinical practice. The co-registration accuracy was significantly influenced by the operator's experience, and significantly poorer in the antero-posterior direction and at the apex.