Effectiveness of Focal Therapy in Men With Prostate Cancer

NCT ID: NCT06223295

Last Updated: 2024-02-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

356 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-02-01

Study Completion Date

2031-02-28

Brief Summary

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In the Netherlands, most men with prostate cancer (PCa) are treated with radical whole-gland treatment, i.e. prostatectomy or radiotherapy. The burden of complications such as incontinence and erectile dysfunction associated with radical treatment is considerable. A recent systematic review by our group has shown that focal therapy of PCa seems to reduce the burden of treatment side-effects in men with intermediate-risk disease, maintaining their quality of life without compromising oncological effectiveness. The costs of side effects that can be prevented are estimated at €5456 per patient, resulting in total expected cost savings of about €22 million per year in The Netherlands. Furthermore, exploration of the benefit-risk balance under patients showed that they are willing to sacrifice some survival for an improvement in quality of life (QoL).

Focal therapy comprises a modern alternative to selectively treat a specific part of the prostate while preserving the rest of the gland. There is, however, a lack of high-quality evidence, and numerous papers therefore recommend to perform a multicenter randomized controlled trial (RCT). The RCT should have long-term follow-up, predefined assessment of cancer-specific and health-related QoL outcome measures, and economic evaluations to inform policymakers regarding cost-effectiveness. This RCT on focal therapy versus usual care is urgently needed to enable focal therapy to overgrow the experimental status, provide the evidence needed for guidelines, and make this available for selected patients who benefit from this strategy. Because of its promising results in other countries, focal therapy is increasingly requested by patients, but due to the lack of high-quality evidence, it is not reimbursed yet. This has been designated by both the PCa patient support group and physicians as a failure of both the market and the funding agencies. The investigators, therefore, aim to perform a high-quality multi-center RCT to provide the evidence needed to decide on reimbursement and implementation of focal therapy in patients with intermediate-risk, unilateral clinically localized PCa in the Netherlands.

Detailed Description

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In the Netherlands, most men with PCa are treated with radical whole-gland treatment, i.e. prostatectomy or a form of radiotherapy. The burden of complications such as incontinence and erectile dysfunction associated with radical treatment is considerable.

A recent systematic review by our group has shown that focal therapy of PCa seems to reduce the burden of treatment side-effects in men with intermediate-risk disease, maintaining their quality of life without compromising oncological effectiveness. The costs of side-effects that can be prevented are estimated at €5456 per patient, resulting in total expected cost savings of about €22 million per year in The Netherlands. Furthermore, exploration of the benefit-risk balance under patients showed that they are willing to sacrifice some survival for an improvement in quality of life (QoL).

Focal therapy comprises a modern alternative to selectively treat a specific part of the prostate while preserving the rest of the gland. There is, however, a lack of high-quality evidence, and numerous papers therefore recommend to perform a multicenter randomized controlled trial (RCT). The RCT should have long-term follow-up, predefined assessment of cancer-specific and health-related QoL outcome measures, and economic evaluations to inform policymakers regarding cost-effectiveness. This RCT on focal therapy versus usual care is urgently needed to enable focal therapy to overgrow the experimental status, provide the evidence needed for guidelines, and make this available for selected patients who benefit from this strategy. Because of its promising results in other countries, focal therapy is increasingly requested by patients, but due to the lack of high-quality evidence, it is not reimbursed yet. This has been designated by both the PCa patient support group and physicians as a failure of both the market and the funding agencies.

At present, all devices that are used in the proposed study are CE approved and no safety issues were reported in IDEAL stage 1 and 2a studies. For high-risk PCa, local radical therapy has been found to significantly improve oncological endpoints. However, for low- and intermediate-risk localized PCa, the different recommended options by guidelines (radical prostatectomy (RP), radiotherapy (RT), or active surveillance (AS)) have similar short- to medium-term oncological outcomes in randomized studies. A PROZIB database search and a KWF report showed that about 65% of the intermediate-risk patients that are eligible for focal therapy currently undergo either RP or RT. Furthermore, brachytherapy is only used to a limited extent (7%) in intermediate-risk patients in the Netherlands, and since it is not offered as a treatment option in the participating hospitals in this proposal, the investigators do not include this option in our study.

Active surveillance is mainly used for low-risk patients rather than for the intermediate-risk patients the investigators are aiming for in this study. Our systematic review concluded that more high-quality evidence is required before focal therapy can become available as a standard treatment. The majority of focal therapy studies were prospective development IDEAL stage 2a studies (feasibility studies), showing the limited adverse impact on functional outcomes and favorable oncological outcomes. Overall, focal therapy studies reported a median of 95% pad-free at 1-year and 85% of the patients had no clinically significant cancer in the treated area, respectively. High-quality multi-center comparative clinical trials, however, appear to be lacking. The appropriate management of patients with recurrent PCa following focal therapy has been an ongoing point of discussion. Marra et al. showed that evidence from assessments of salvage treatments after focal therapy failure is low and is derived from four retrospective salvage series. Available salvage options after focal therapy include RP and RT. Overall oncological outcomes are acceptable, although biochemical recurrence is slightly higher compared to primary PCa treatment, probably because of the higher aggressiveness of recurrent/persistent PCa. Functional outcomes and complications are not markedly worse compared to primary treatment. Salvage RP and salvage RT, therefore, seem feasible treatment options with acceptable oncological control and functional outcomes. Thus, re-treatment with salvage radiotherapy or salvage surgery remains a clinical option after focal therapy failure. Experience from other countries and our qualitative research on this topic taught us that many patients will consciously opt for an initial focal therapy to maintain their quality of life and because they can be treated later when deemed necessary with the other options.

All patients included in our trial will undergo intensive follow-up. Patients undergoing focal therapy will undergo quarterly PSA measurement and yearly prostate MRI, followed by a prostate biopsy after 12 months and thereafter if indicated based on the MRI. Since focal therapy is a one-time intervention, there will be no patients left in treatment or that require alternative fallback treatments. Ablation devices can be returned after the completion of the trial. The disposables are single-use and are depreciated. There are no specific costs associated with the discontinuation of focal treatment after the trial.

The investigators, therefore, aim to perform a high-quality multi-center RCT to provide the evidence needed to decide on reimbursement and implementation of focal therapy in patients with intermediate-risk, unilateral clinically localized PCa in the Netherlands. This study is funded by a national grant (Veelbelovende Zorg) from the Dutch Health Institute (Zorginstituut Nederland).

Conditions

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Prostate Cancer Prostate Neoplasm

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Focal therapy

Patients in this group will receive focal therapy, i.e. TULSA, IRE or Hifu.

Group Type ACTIVE_COMPARATOR

Focal therapy

Intervention Type PROCEDURE

Focal therapy selectively treats a specific part of the prostate while preserving the rest of the gland in men with prostate cancer.

Focal therapy with ultrasound ablation (HIFU/TULSA) or irreversible electroporation (IRE) followed by an intensive MRI follow-up scheme at 12, 24, 36, 48 and 60 months, prostate biopsy at 12 months (and also when indicated) and PSA monitoring

Usual care

Patients in this group will receive usual care for prostate cancer, i.e. radical prostatectomy or radiotherapy

Group Type ACTIVE_COMPARATOR

Usual care

Intervention Type PROCEDURE

standard radical treatment; prostatectomy or radiotherapy with follow-up according international guidelines (PSA monitoring and imaging when indicated).

Interventions

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Focal therapy

Focal therapy selectively treats a specific part of the prostate while preserving the rest of the gland in men with prostate cancer.

Focal therapy with ultrasound ablation (HIFU/TULSA) or irreversible electroporation (IRE) followed by an intensive MRI follow-up scheme at 12, 24, 36, 48 and 60 months, prostate biopsy at 12 months (and also when indicated) and PSA monitoring

Intervention Type PROCEDURE

Usual care

standard radical treatment; prostatectomy or radiotherapy with follow-up according international guidelines (PSA monitoring and imaging when indicated).

Intervention Type PROCEDURE

Other Intervention Names

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TULSA IRE Hifu Radical prostatectomy Radiotherapy

Eligibility Criteria

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Inclusion Criteria

* Gleason score of 7 (3 + 4 or 4 + 3; ISUP grade 2/3)
* PSA level of ≤ 20 ng/ml
* Clinical stage ≤ T2b disease
* Life expectancy of ≥ 10 years
* Men with a prostate size ≤ 5 cm in sagittal length and ≤ 6 cm in axial length
* Fit, eligible, and normally destined for radical surgery or radiotherapy
* No concomitant cancer
* No previous treatment of their prostate
* An understanding of the Dutch language sufficient to receive written and verbal information about the trial, its consent process and the study questionnaires

Exclusion Criteria

* Unfit for general anesthesia or radical surgery
* Low volume low-risk disease (≤4mm Gleason score of ≤ 6 / ISUP grade 1)
* High-risk disease (Gleason score of ≥ 8 / ISUP grade \>3)
* Clinical T3 disease (extracapsular PCa)
* Men who have received previous active therapy for PCa.
* Men with evidence of extraprostatic disease.
* Men with an inability to tolerate a transrectal ultrasound.
* Cardiac pacemaker
* Metal implants/stents in the urethra or prostate.
* ASA ≥4
* Prostatic calcification/cysts that interfere with effective delivery of TULSA/HIFU based on MRCT.
* Men with renal impairment and a glomerular filtration rate (GFR) of \< 30 ml/minute/1.73 m2.
* Unable to give consent to participate in the trial, as judged by the attending clinicians
Minimum Eligible Age

45 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Isala

OTHER

Sponsor Role collaborator

Amsterdam UMC, location VUmc

OTHER

Sponsor Role collaborator

St. Antionius Hospital

UNKNOWN

Sponsor Role collaborator

Hifu kliniek

UNKNOWN

Sponsor Role collaborator

Dutch National Health Care Institute

OTHER

Sponsor Role collaborator

ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role collaborator

Nederlandse Vereniging voor Radiotherapie en Oncologie

UNKNOWN

Sponsor Role collaborator

Wetenschapscommissie interventieradiologie/Nederlandse vereniging voor interventieradiologie

UNKNOWN

Sponsor Role collaborator

Inspire2live

UNKNOWN

Sponsor Role collaborator

Prostaatkankerstichting

UNKNOWN

Sponsor Role collaborator

Nederlandse Vereniging voor Urologie

UNKNOWN

Sponsor Role collaborator

Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Radboud University Medical Centre

Nijmegen, Gelderland, Netherlands

Site Status RECRUITING

Hifu kliniek

Etten-Leur, North Brabant, Netherlands

Site Status NOT_YET_RECRUITING

Amsterdam UMC

Amsterdam, North Holland, Netherlands

Site Status NOT_YET_RECRUITING

Isala klinieken

Zwolle, Overijssel, Netherlands

Site Status NOT_YET_RECRUITING

St. Antonius hospital

Nieuwegein, Utrecht, Netherlands

Site Status NOT_YET_RECRUITING

Countries

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Netherlands

Central Contacts

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Lauren te Molder

Role: CONTACT

+31243611111

Facility Contacts

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Lauren te Molder

Role: primary

+31243618766

References

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Haglind E, Carlsson S, Stranne J, Wallerstedt A, Wilderang U, Thorsteinsdottir T, Lagerkvist M, Damber JE, Bjartell A, Hugosson J, Wiklund P, Steineck G; LAPPRO steering committee. Urinary Incontinence and Erectile Dysfunction After Robotic Versus Open Radical Prostatectomy: A Prospective, Controlled, Nonrandomised Trial. Eur Urol. 2015 Aug;68(2):216-25. doi: 10.1016/j.eururo.2015.02.029. Epub 2015 Mar 12.

Reference Type BACKGROUND
PMID: 25770484 (View on PubMed)

Hopstaken JS, Bomers JGR, Sedelaar MJP, Valerio M, Futterer JJ, Rovers MM. An Updated Systematic Review on Focal Therapy in Localized Prostate Cancer: What Has Changed over the Past 5 Years? Eur Urol. 2022 Jan;81(1):5-33. doi: 10.1016/j.eururo.2021.08.005. Epub 2021 Sep 4.

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Watson V, McCartan N, Krucien N, Abu V, Ikenwilo D, Emberton M, Ahmed HU. Evaluating the Trade-Offs Men with Localized Prostate Cancer Make between the Risks and Benefits of Treatments: The COMPARE Study. J Urol. 2020 Aug;204(2):273-280. doi: 10.1097/JU.0000000000000754. Epub 2020 Jan 22.

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Chin JL, Billia M, Relle J, Roethke MC, Popeneciu IV, Kuru TH, Hatiboglu G, Mueller-Wolf MB, Motsch J, Romagnoli C, Kassam Z, Harle CC, Hafron J, Nandalur KR, Chronik BA, Burtnyk M, Schlemmer HP, Pahernik S. Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Tissue in Patients with Localized Prostate Cancer: A Prospective Phase 1 Clinical Trial. Eur Urol. 2016 Sep;70(3):447-55. doi: 10.1016/j.eururo.2015.12.029. Epub 2016 Jan 6.

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Marra G, Valerio M, Emberton M, Heidenreich A, Crook JM, Bossi A, Pisters LL. Salvage Local Treatments After Focal Therapy for Prostate Cancer. Eur Urol Oncol. 2019 Sep;2(5):526-538. doi: 10.1016/j.euo.2019.03.008. Epub 2019 Apr 15.

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Nathan A, Ng A, Mitra A, Sooriakumaran P, Davda R, Patel S, Fricker M, Kelly J, Shaw G, Rajan P, Sridhar A, Nathan S, Payne H. Comparative Effectiveness Analyses of Salvage Prostatectomy and Salvage Radiotherapy Outcomes Following Focal or Whole-Gland Ablative Therapy (High-Intensity Focused Ultrasound, Cryotherapy or Electroporation) for Localised Prostate Cancer. Clin Oncol (R Coll Radiol). 2022 Jan;34(1):e69-e78. doi: 10.1016/j.clon.2021.10.012. Epub 2021 Nov 3.

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Reference Type BACKGROUND
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Other Identifiers

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2023-16261

Identifier Type: -

Identifier Source: org_study_id

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