Focal Therapy for Prostate Cancer Using HIFU
- Conditions
- Male Erectile DisorderTherapy-related ToxicityProstate CancerUrinary Incontinence
- Interventions
- Other: questionnaire administrationProcedure: assessment of therapy complicationsProcedure: high-intensity focused ultrasound ablationProcedure: multiparametric magnetic resonance imagingProcedure: quality-of-life assessmentProcedure: transperineal prostate biopsyProcedure: transrectal prostate biopsy
- Registration Number
- NCT01194648
- Lead Sponsor
- University College, London
- Brief Summary
RATIONALE: Prospective trials using hemi-ablation with high intensity focused ultrasound (HIFU) (Sonablate 500) have demonstrated feasibility, safety, and encouraging functional outcomes and early cancer control with 90% of men achieving trifecta status (no erectile dysfunction, leak-free pad-free continence, cancer control). However, these trials have involved small numbers of patients with men selected for good baseline function. A multi-centre prospective trial within a larger cohort of men that better represents the patient population with prostate cancer (external validity) is required.
- Detailed Description
Verification of a new therapy as favourable, or equivalent, in outcome to 'standard' care is ideally sought through comparison with another matched control group. Randomised controlled trials (RCTs) offer the best method for minimising systematic bias and revealing the true effect of an intervention or drug. However, RCTs involving treatments of localised prostate cancer have had a historically poor patient uptake, as the reference 'gold' standard of care is not known. In addition, RCTs are expensive to run and involve huge infra-structural support. A number of trials in the USA have been forced to close due to lack of recruitment. The ProStart trial in the UK has also had to close for the same reason. It has been acknowledged by the Food and Drug Agency in the USA that comparative randomized trials will be problematic in this area due to lack of physician and patient equipoise. A randomized trial may be feasible if a pragmatic design is adopted but prior to acceptance of such a design, the number of centres with expertise in this complex intervention (mp-MRI, TTPM, focal HIFU) will need to be increased.
Observational studies are a commonly used alternative to ascertain the effectiveness of a treatment. They are used to observe a treatment effect in a selected group of patients who are presumed to derive benefit from the treatment given. Although methodologically not as robust, and therefore prone to bias, they have some benefits over RCTs. The principal ones are those of enhanced external validity (many patients do not wished to be randomised and therefore refuse participation), and more rapid accrual compared to a randomised design. For this reasons, a single arm medium term follow-up cohort intervention study has been designed. At the time of writing the safety and tolerability aspects of focal therapy by HIFU are known as a result of the Phase I/II studies carried out at UCLH. The results have been presented and exist in the public domain in abstract form but have not yet been published (presented in tables above). These early studies were powered to detect a change in the proportion of men who could obtain an erection sufficient for penetration compared to their status prior to their treatment. The very low event rate for both erectile dysfunction and incontinence indicates that the 'proof of concept' has been demonstrated for focal therapy. Moreover, we can be relatively confident that, in expert hands, focal HIFU is safe. Therefore, a multi-centre study is now required involving a larger group of patients for the following reasons:
1. To evaluate medium term cancer control using histological parameters. Stage two of INDEX will evaluate conversion to radical and systemic therapies and link men to national databases to determine survival in 5 and 10 years.
2. To confirm that focal therapy can lead to low rates of genitourinary and rectal toxicity and minimal impact on quality of life within a large and more representative cohort of patients (greater precision around outcome measures).
3. To demonstrate that the skills (characterization through template prostate mapping and MRI as well as the treatment related skills) acquired by the team at UCLH are indeed transferable to other providers.
4. To calculate costs of care and to model potential cost-effectiveness in comparison to alternative therapies. If this single arm intervention study demonstrates acceptable outcomes to support the findings of the Phase I/II studies, it is anticipated that this preliminary study will lead onto a Phase III evaluation of focal therapy, prior to more widespread use of this technology.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 354
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description High Intensity Focused Ultrasound assessment of therapy complications HIFU, the Intervention High Intensity Focused Ultrasound multiparametric magnetic resonance imaging HIFU, the Intervention High Intensity Focused Ultrasound questionnaire administration HIFU, the Intervention High Intensity Focused Ultrasound quality-of-life assessment HIFU, the Intervention High Intensity Focused Ultrasound high-intensity focused ultrasound ablation HIFU, the Intervention High Intensity Focused Ultrasound transperineal prostate biopsy HIFU, the Intervention High Intensity Focused Ultrasound transrectal prostate biopsy HIFU, the Intervention
- Primary Outcome Measures
Name Time Method Conversion to radical therapy and/or requiring systemic therapy and/or developing metastases and/or dying of prostate cancer 10 years To determine the proportion of men converting to radical therapy and/or requiring systemic therapy and/or developing metastases and/or dying of prostate cancer following focal therapy for localised prostate cancer using HIFU
- Secondary Outcome Measures
Name Time Method rate of loss of ejaculation 24 months rate of loss of ejaculation (as determined by IIEF-15 questionnaire)
rate of erectile dysfunction 24 months The presence of severe erectile dysfunction at 24 months, as measured by the IIEF-5 questionnaire with or without the use of phosphodiesterase-5 inhibitors, in those with absence of severe erectile dysfunction at baseline
rate of urinary incontinence (pad free, leak free and pad-free alone) 24 months Presence of urinary incontinence (any pad usage plus any leakage of urine) as determined by the UCLA-EPIC urinary continence questionnaire, at 24 months, in those men with no urinary incontinence at baseline
rate of pain during intercourse 24 months rate of pain during intercourse (as determined by IIEF-15 questionnaire)
rate of loss of orgasm 24 months rate of loss of orgasm (as determined by IIEF-15 questionnaire)
time to return of erectile function 24 months Time to return of erectile function (absence of severe ED on IIEF-15 questionnaire)
time to return of continence (pad free, leak free and pad-free alone) 24 months Time to return of urinary continence (as determined by UCLA-EPIC Urinary domain questionnaire)
general health related quality of life 24 months General and prostate health related quality of life measured using EQ-5D Quality of Life questionnaire
proportion of men achieving trifecta status at 24 months 24 months Achievement of trifecta status (no severe ED, pad-free leak-free continence, cancer control with absence of clinically significant cancer) at 24 months in those men with good baseline function
rate of secondary prostate cancer intervention (prostatectomy, radiotherapy, androgen ablation, whole-gland HIFU or cryosurgery) 24 months rate of secondary prostate cancer intervention (prostatectomy, radiotherapy, androgen ablation, whole-gland HIFU or cryosurgery)
number of men using phosphodiesterase-5 inhibitors to maintain erectile function 24 months Need for phosphodiesterase-5 inhibitors to maintain erectile function sufficient for penetration up to 24 months
biochemical (PSA) kinetics including determining the optimal biochemical definition of failure 24 months biochemical (PSA) kinetics including determining the optimal biochemical definition of
rate of lower urinary tract symptoms 24 months Grading of lower urinary tract symptoms as determined by IPSS scores
rate of bowel toxicity 24 months UCLA-EPIC Bowel Function Questionnaire
anxiety levels 24 months EQ-5D Quality of Life Questionnaire
proportion of men achieving trifecta status at 12 months 12months Achievement of trifecta status (no severe ED, pad-free leak-free continence, cancer control with absence of clinically significant cancer) at 12 months in those men with good baseline function
risk factors for failure defined as a) presence of any cancer and b) clinically significant cancer at study end 24 months risk factors for failure defined as a) presence of any cancer and b) clinically significant
describe composite outcomes of failure 24 months describe composite outcomes of failure
Cost-effectiveness 10 years To determine the costs of treatment and model potential cost effectiveness using comparative cancer control and functional outcomes at 10 years compared to other cohort trials involving the management of localized prostate cancer
Trial Locations
- Locations (1)
University College London
🇬🇧London, England, United Kingdom