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.

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.

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.

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.

Whole-gland ablation of localized prostate cancer with high-intensity focused ultrasound: oncologic outcomes and morbidity in 1002 patients.

BACKGROUND: High-intensity focused ultrasound (HIFU) is a nonsurgical therapy for selected patients with localized prostate cancer (PCa). OBJECTIVE: The long-term oncologic and morbidity outcomes of primary HIFU therapy for localized PCa were evaluated in a prospective, single-arm, single-institution cohort study. DESIGN, SETTING, AND PARTICIPANTS: Participants were patients treated with HIFU for localized PCa from 1997 to 2009. Excluded were patients with local recurrence following radiotherapy. A second HIFU session was systematically performed in patients with biopsy-proven local recurrence. INTERVENTION: Whole-gland prostate ablation with transrectal HIFU. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Incontinence was assessed using the Ingelman-Sundberg score, and potency was assessed using the five-item version of the International Index of Erectile Function (IIEF-5) scores. Primary outcomes were survival rates (biochemical-free, cancer-specific, metastasis-free, and overall survival). Secondary outcomes were morbidity rates. Median follow-up was 6.4 yr (range: 0.2-13.9). The Kaplan-Meier method was used to determine survival estimates, and multivariate analysis was used to determine predictive factors of biochemical progression. RESULTS AND LIMITATIONS: A total of 1002 patients were included. The median nadir prostate-specific antigen (PSA) was 0.14 ng/ml, with 63% of patients reaching a nadir PSA ≤0.3 ng/ml. Sixty percent of patients received one HIFU session, 38% received two sessions, and 2% received three sessions. The 8-yr biochemical-free survival rates (Phoenix definition) were 76%, 63%, and 57% for low-, intermediate-, and high-risk patients, respectively (p < 0.001). 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. Limitations included the fact that the study was a single-arm study without a comparison group, technological improvements, changes in surgical protocol during the study, and the use of ADT to downsize the prostate in 39% of patients. CONCLUSIONS: HIFU is a potentially effective treatment of localized PCa, with a low PCa-specific mortality rate and a high MFSR at 10 yr as well as acceptable morbidity.

Locally recurrent prostate cancer after initial radiation therapy: early salvage high-intensity focused ultrasound improves oncologic outcomes.

PURPOSE: To evaluate pre-operative prognostic risk factors to predict oncologic outcome of Salvage High-Intensity Focused Ultrasound (S-HIFU) for radiorecurrent prostate cancer (PCa). METHODS AND MATERIALS: A total of 290 men with biopsy-confirmed locally radiorecurrent PCa, underwent S-HIFU. D'Amico risk group before external beam radiotherapy (EBRT), Prostate Specific Antigen (PSA), estimated Gleason score prior HIFU and post HIFU biopsies were analyzed for predictive utility of local cancer control, cancer-specific, metastasis free, and progression free survival rates (PFSR). RESULTS: Local cancer control with negative biopsy results was obtained in 81% of the 208 patients who underwent post-S-HIFU biopsies. Median PSA nadir was 0.14 ng/ml and 127 patients did not require androgen deprivation therapy (ADT). The mean follow up was 48 months for cancer-specific survival rates. The cancer-specific and metastasis-free survival rates at 7 years were 80% and 79.6% respectively. The PFSR was significantly influenced by: the pre-HIFU PSA level (hazard ratio (HR): 1.09, 95% CI 1.04-1.13), a Gleason score ≥8 versus ≤6 (HR: 1.17, 95% CI 1.03-1.3), and a previous ADT (HR: 1.28, 95% CI 1.09-1.46). The rates of recto-urethral fistula (0.4%) and grade II/III incontinence (19.5%) indicate significant reduction in serious side effects with use of dedicated post-radiation acoustic parameters compared with standard parameters. CONCLUSION: S-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.