Prostate CancerENFORCENCT06223295
Effectiveness of Focal Therapy in Men With Prostate Cancer
A study testing Focal therapy in people with Prostate Cancer and Prostate Neoplasm, run by Radboud University Medical Center at 5 sites in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 45 years and older, men only
- Conditions the study is for
- Prostate Cancer, Prostate Neoplasm
- What is being tested?
- Focal therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 356 participants
- Where
- 5 sitesNetherlands
- Study dates
- 1 Feb 2024to Feb 2031
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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.
Show all 13Show fewer
- 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
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
Netherlands5 sites, 5 recruiting
- Not yet recruiting
Amsterdam UMC
Amsterdam, North Holland
- Not yet recruiting
Hifu kliniek
Etten-Leur, North Brabant
- Not yet recruiting
St. Antonius hospital
Nieuwegein, Utrecht
- Recruiting
Radboud University Medical Centre
Nijmegen, Gelderland, 6525GA
Lauren te Molder, +31243618766, Lauren.teMolder@radboudumc.nl
Jurgen Fütterer
- Not yet recruiting
Isala klinieken
Zwolle, Overijssel
About this study
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.
Read the detailed description
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
- Prostate Cancer, Prostate Neoplasm
- Being tested
- Focal therapy, Usual care
- Keywords
- prostate neoplasm, focal therapy, prostate cancer
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Focal therapyProcedure or surgery
Also called TULSA, IRE, Hifu
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 careProcedure or surgery
Also called Radical prostatectomy, Radiotherapy
standard radical treatment; prostatectomy or radiotherapy with follow-up according international guidelines (PSA monitoring and imaging when indicated).
| Study group | Role | What they receive |
|---|---|---|
| Focal therapy | Active comparator | Patients in this group will receive focal therapy, i.e. TULSA, IRE or Hifu. Receives: Procedure: Focal therapy |
| Usual care | Active comparator | Patients in this group will receive usual care for prostate cancer, i.e. radical prostatectomy or radiotherapy Receives: Procedure: Usual care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oncological effectiveness (non-inferiority) defined as treatment failure
i.e. pathologically proven recurrent disease and/or the indication for retreatment with salvage treatment (RP, RT or systemic treatment or RT) in the focal therapy group and as biochemical recurrence and/or salvage treatment in the usual care group
Measured: 36 months
Quality of life (superiority) measured with Functional Assessment of Cancer Therapy-Prostate questionnaire
Compare quality of life between the two arms measured with the FACT-P questionnaire. FACT-P scores of the subscales vary between 0-24 and 0-28, the total score is between 0-156. The higher the score, the better.
Measured: 12 months
Secondary outcomes (15)
Metastasis-free survival
Metastasis-free survival as a validated surrogate endpoint of overall survival, comparing the proportion of patients between the arms who are free from metastatic disease.
Measured: at baseline, 3, 6, 12, 24, 36, 48 and 60 months
Health-related quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for prostate cancer
Compare quality of life measurements between the two arms using the EORTC QLQ-PR25 for sexual symptoms a higher score on the functional scales means a higher level of functioning, but on the symptomatic scales, a higher score means a greater severity of symptoms
Measured: at baseline, 3, 6, 12, 24, 36, 48 and 60 months
Health-related quality of life using the International Consultation on Incontinence Questionnaire
Quality of life measurements using the ICIQ-SF. Score ranges between1 and 21, a higher score means a greater severity of symptoms.
Measured: at baseline, 3, 6, 12, 24, 36, 48 and 60 months
Health-related quality of life regarding urinary symptoms using the International Prostate Symptom Score questionnaire
Compare quality of life measurements between the two arms using the IPSS The score ranges between 0 and 35, a higher score means a greater severity of symptoms
Measured: at baseline, 3, 6, 12, 24, 36, 48 and 60 months
Health-related quality of life using the Sexual Health Inventory for Men International Index of Erectile Function-5 questionnaire
Compare quality of life measurements between the two arms regarding sexual function using the SHIM IIEF-5 questionnaire, the score ranges between 8 and 25, a higher score means lesser severity of symptoms.
Measured: at baseline, 3, 6, 12, 24, 36, 48 and 60 months
Health-related quality of life using the 5-dimension health-related quality of life from the uroQol group
Quality of life measurements regarding mobility, self-care, usual activities, pain/discomfort, anxiety/depression using the EuroQol 5D 5level questionnaire
Measured: at baseline, 3, 6, 12, 24, 36, 48 and 60 months
Disease progression
Measured: 60 months
Disease specific mortality
Compare the mortality between the two arms regarding prostate cancer
Measured: 60 months
All-cause mortality
Compare the overall mortality between the two arms.
Measured: 60 months
Operating time
Compare the total time of the procedure between the two arms.
Measured: Immediately after the procedure
Hospital care stay
Compare the length of the hospital stay between the two arms.
Measured: Immediately after procedure
Pathology results after biopsy and/or radical prostatectomy
- Pathology results after biopsy and/or radical prostatectomy will be summarized using descriptive statistics, primarily the frequency and proportion of events.
Measured: 60 months
Adverse events
- Treatment-related complications will be recorded according to the Clavien-Dindo classification. We will calculate both an overall mean risk difference and 95% confidence interval as well as a mean risk difference per item, and their corresponding 95% CI
Measured: 60 months
Cost-effectiveness will be measured using the iMTA Medical Consumption Questionnaire
Costs will be calculated according to the Dutch guideline for costing research, by multiplying resource use with the corresponding unit costs. Average costs will be calculated in both groups, and differences will be calculated inclusive of 95% confidence intervals. Effectiveness will be measured in terms of quality-adjusted life years (QALYs).
Measured: 60 months
Cost-effectiveness will be measured using the IMTA Productivity Cost Questionnaire
Costs will be calculated according to the Dutch guideline for costing research, by multiplying resource use with the corresponding unit costs. Average costs will be calculated in both groups, and differences will be calculated inclusive of 95% confidence intervals. Effectiveness will be measured in terms of quality-adjusted life years (QALYs).
Measured: 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2024
- Study start1 Feb 2024
- Primary completionAug 2029 (estimated)
- Study completionFeb 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 356 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Isala, Amsterdam UMC, location VUmc, St. Antionius Hospital, Hifu kliniek, Dutch National Health Care Institute, ZonMw: The Netherlands Organisation for Health Research and Development, Nederlandse Vereniging voor Radiotherapie en Oncologie, Wetenschapscommissie interventieradiologie/Nederlandse vereniging voor interventieradiologie, Inspire2live, Prostaatkankerstichting, Nederlandse Vereniging voor Urologie
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06223295
- Sponsor's protocol ID
- 2023-16261
- Other IDs
- 2023
- Acronym
- ENFORCE
- Status last verified
- Aug 2023
- First submitted
- 7 Sep 2023
- Last updated
- 20 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 25770484Hopstaken 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.
PubMed 34489140de Bekker-Grob EW, Bliemer MC, Donkers B, Essink-Bot ML, Korfage IJ, Roobol MJ, Bangma CH, Steyerberg EW. Patients' and urologists' preferences for prostate cancer treatment: a discrete choice experiment. Br J Cancer. 2013 Aug 6;109(3):633-40. doi: 10.1038/bjc.2013.370. Epub 2013 Jul 16.
PubMed 23860533Watson 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.
PubMed 31967521Blazevski A, Scheltema MJ, Yuen B, Masand N, Nguyen TV, Delprado W, Shnier R, Haynes AM, Cusick T, Thompson J, Stricker P. Oncological and Quality-of-life Outcomes Following Focal Irreversible Electroporation as Primary Treatment for Localised Prostate Cancer: A Biopsy-monitored Prospective Cohort. Eur Urol Oncol. 2020 Jun;3(3):283-290. doi: 10.1016/j.euo.2019.04.008. Epub 2019 May 16.
PubMed 31103721Chin 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.
PubMed 26777228Bonekamp D, Wolf MB, Roethke MC, Pahernik S, Hadaschik BA, Hatiboglu G, Kuru TH, Popeneciu IV, Chin JL, Billia M, Relle J, Hafron J, Nandalur KR, Staruch RM, Burtnyk M, Hohenfellner M, Schlemmer HP. Twelve-month prostate volume reduction after MRI-guided transurethral ultrasound ablation of the prostate. Eur Radiol. 2019 Jan;29(1):299-308. doi: 10.1007/s00330-018-5584-y. Epub 2018 Jun 25.
PubMed 29943185Ramsay E, Mougenot C, Staruch R, Boyes A, Kazem M, Bronskill M, Foster H, Sugar L, Haider M, Klotz L, Chopra R. Evaluation of Focal Ablation of Magnetic Resonance Imaging Defined Prostate Cancer Using Magnetic Resonance Imaging Controlled Transurethral Ultrasound Therapy with Prostatectomy as the Reference Standard. J Urol. 2017 Jan;197(1):255-261. doi: 10.1016/j.juro.2016.06.100. Epub 2016 Aug 18.
PubMed 27545572Marra 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.
PubMed 31412013Nathan 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.
PubMed 34740477Gharzai LA, Jiang R, Wallington D, Jones G, Birer S, Jairath N, Jaworski EM, McFarlane MR, Mahal BA, Nguyen PL, Sandler H, Morgan TM, Reichert ZR, Alumkal JJ, Mehra R, Kishan AU, Fizazi K, Halabi S, Schaeffer EM, Feng FY, Elliott D, Dess RT, Jackson WC, Schipper MJ, Spratt DE. Intermediate clinical endpoints for surrogacy in localised prostate cancer: an aggregate meta-analysis. Lancet Oncol. 2021 Mar;22(3):402-410. doi: 10.1016/S1470-2045(20)30730-0.
PubMed 33662287Skolarus TA, Dunn RL, Sanda MG, Chang P, Greenfield TK, Litwin MS, Wei JT; PROSTQA Consortium. Minimally important difference for the Expanded Prostate Cancer Index Composite Short Form. Urology. 2015 Jan;85(1):101-5. doi: 10.1016/j.urology.2014.08.044.
PubMed 25530370Tay KJ, Scheltema MJ, Ahmed HU, Barret E, Coleman JA, Dominguez-Escrig J, Ghai S, Huang J, Jones JS, Klotz LH, Robertson CN, Sanchez-Salas R, Scionti S, Sivaraman A, de la Rosette J, Polascik TJ. Patient selection for prostate focal therapy in the era of active surveillance: an International Delphi Consensus Project. Prostate Cancer Prostatic Dis. 2017 Sep;20(3):294-299. doi: 10.1038/pcan.2017.8. Epub 2017 Mar 28.
PubMed 28349978Cella D, Nichol MB, Eton D, Nelson JB, Mulani P. Estimating clinically meaningful changes for the Functional Assessment of Cancer Therapy--Prostate: results from a clinical trial of patients with metastatic hormone-refractory prostate cancer. Value Health. 2009 Jan-Feb;12(1):124-9. doi: 10.1111/j.1524-4733.2008.00409.x. Epub 2008 Jul 18.
PubMed 18647260Te Molder LPW, Sedelaar JPM, Bomers JGR, Boomsma MF, de Haan TD, van Melick HHE, Meijerink MR, Beerlage HP, van Aubel O, Collette ER, Grutters JPC, Hannink G, Rovers MM, Futterer JJ; ENFORCE Focal consortium. (Cost-)effectiveness of focal therapy versus radical therapy (standard of care) in the treatment of men with intermediate-risk prostate cancer: study protocol for the ENFORCE focal randomised controlled trial. BMJ Open. 2026 Jul 8;16(7):e117276. doi: 10.1136/bmjopen-2026-117276.
PubMed 42419881
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness of Focal Therapy in Men With Prostate Cancer
- ClinicalTrials.gov ID
- NCT06223295
- Acronym / sponsor ID
- ENFORCE / 2023-16261
- Conditions
- Prostate Cancer, Prostate Neoplasm
- Keywords
- prostate neoplasm, focal therapy, prostate cancer
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 356 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Isala, Amsterdam UMC, location VUmc, St. Antionius Hospital, Hifu kliniek, Dutch National Health Care Institute, ZonMw: The Netherlands Organisation for Health Research and Development, Nederlandse Vereniging voor Radiotherapie en Oncologie, Wetenschapscommissie interventieradiologie/Nederlandse vereniging voor interventieradiologie, Inspire2live, Prostaatkankerstichting, Nederlandse Vereniging voor Urologie
- Study start
- 1 Feb 2024 (actual)
- Primary completion
- Aug 2029 (estimated)
- Study completion
- Feb 2031 (estimated)
- First posted
- 25 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Focal therapy | Active comparator | Procedure: Focal therapyPatients in this group will receive focal therapy, i.e. TULSA, IRE or Hifu. |
| Usual care | Active comparator | Procedure: Usual carePatients in this group will receive usual care for prostate cancer, i.e. radical prostatectomy or radiotherapy |
Who may qualify
- Ages
- 45 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Focal therapyAlso: TULSA, IRE, HifuFocal 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 | Procedure or surgery | Focal therapy |
| Usual careAlso: Radical prostatectomy, Radiotherapystandard radical treatment; prostatectomy or radiotherapy with follow-up according international guidelines (PSA monitoring and imaging when indicated). | Procedure or surgery | Usual care |
Primary outcome
Oncological effectiveness (non-inferiority) defined as treatment failure
Time frame: 36 months
i.e. pathologically proven recurrent disease and/or the indication for retreatment with salvage treatment (RP, RT or systemic treatment or RT) in the focal therapy group and as biochemical recurrence and/or salvage treatment in the usual care group
Quality of life (superiority) measured with Functional Assessment of Cancer Therapy-Prostate questionnaire
Time frame: 12 months
Compare quality of life between the two arms measured with the FACT-P questionnaire. FACT-P scores of the subscales vary between 0-24 and 0-28, the total score is between 0-156. The higher the score, the better.
15 secondary outcomes
Metastasis-free survival
Time frame: at baseline, 3, 6, 12, 24, 36, 48 and 60 months
Health-related quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for prostate cancer
Time frame: at baseline, 3, 6, 12, 24, 36, 48 and 60 months
Health-related quality of life using the International Consultation on Incontinence Questionnaire
Time frame: at baseline, 3, 6, 12, 24, 36, 48 and 60 months
Health-related quality of life regarding urinary symptoms using the International Prostate Symptom Score questionnaire
Time frame: at baseline, 3, 6, 12, 24, 36, 48 and 60 months
Health-related quality of life using the Sexual Health Inventory for Men International Index of Erectile Function-5 questionnaire
Time frame: at baseline, 3, 6, 12, 24, 36, 48 and 60 months
Health-related quality of life using the 5-dimension health-related quality of life from the uroQol group
Time frame: at baseline, 3, 6, 12, 24, 36, 48 and 60 months
Disease progression
Time frame: 60 months
Disease specific mortality
Time frame: 60 months
All-cause mortality
Time frame: 60 months
Operating time
Time frame: Immediately after the procedure
Hospital care stay
Time frame: Immediately after procedure
Pathology results after biopsy and/or radical prostatectomy
Time frame: 60 months
Adverse events
Time frame: 60 months
Cost-effectiveness will be measured using the iMTA Medical Consumption Questionnaire
Time frame: 60 months
Cost-effectiveness will be measured using the IMTA Productivity Cost Questionnaire
Time frame: 60 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2024.
- Background: PubMed 25770484Haglind 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.
- Background: PubMed 34489140Hopstaken 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.
- Background: PubMed 23860533de Bekker-Grob EW, Bliemer MC, Donkers B, Essink-Bot ML, Korfage IJ, Roobol MJ, Bangma CH, Steyerberg EW. Patients' and urologists' preferences for prostate cancer treatment: a discrete choice experiment. Br J Cancer. 2013 Aug 6;109(3):633-40. doi: 10.1038/bjc.2013.370. Epub 2013 Jul 16.
- Background: PubMed 31967521Watson 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.
- Background: PubMed 31103721Blazevski A, Scheltema MJ, Yuen B, Masand N, Nguyen TV, Delprado W, Shnier R, Haynes AM, Cusick T, Thompson J, Stricker P. Oncological and Quality-of-life Outcomes Following Focal Irreversible Electroporation as Primary Treatment for Localised Prostate Cancer: A Biopsy-monitored Prospective Cohort. Eur Urol Oncol. 2020 Jun;3(3):283-290. doi: 10.1016/j.euo.2019.04.008. Epub 2019 May 16.
- Background: PubMed 26777228Chin 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.
- Background: PubMed 29943185Bonekamp D, Wolf MB, Roethke MC, Pahernik S, Hadaschik BA, Hatiboglu G, Kuru TH, Popeneciu IV, Chin JL, Billia M, Relle J, Hafron J, Nandalur KR, Staruch RM, Burtnyk M, Hohenfellner M, Schlemmer HP. Twelve-month prostate volume reduction after MRI-guided transurethral ultrasound ablation of the prostate. Eur Radiol. 2019 Jan;29(1):299-308. doi: 10.1007/s00330-018-5584-y. Epub 2018 Jun 25.
- Background: PubMed 27545572Ramsay E, Mougenot C, Staruch R, Boyes A, Kazem M, Bronskill M, Foster H, Sugar L, Haider M, Klotz L, Chopra R. Evaluation of Focal Ablation of Magnetic Resonance Imaging Defined Prostate Cancer Using Magnetic Resonance Imaging Controlled Transurethral Ultrasound Therapy with Prostatectomy as the Reference Standard. J Urol. 2017 Jan;197(1):255-261. doi: 10.1016/j.juro.2016.06.100. Epub 2016 Aug 18.
- Background: PubMed 31412013Marra 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.
- Background: PubMed 34740477Nathan 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.
- Background: PubMed 33662287Gharzai LA, Jiang R, Wallington D, Jones G, Birer S, Jairath N, Jaworski EM, McFarlane MR, Mahal BA, Nguyen PL, Sandler H, Morgan TM, Reichert ZR, Alumkal JJ, Mehra R, Kishan AU, Fizazi K, Halabi S, Schaeffer EM, Feng FY, Elliott D, Dess RT, Jackson WC, Schipper MJ, Spratt DE. Intermediate clinical endpoints for surrogacy in localised prostate cancer: an aggregate meta-analysis. Lancet Oncol. 2021 Mar;22(3):402-410. doi: 10.1016/S1470-2045(20)30730-0.
- Background: PubMed 25530370Skolarus TA, Dunn RL, Sanda MG, Chang P, Greenfield TK, Litwin MS, Wei JT; PROSTQA Consortium. Minimally important difference for the Expanded Prostate Cancer Index Composite Short Form. Urology. 2015 Jan;85(1):101-5. doi: 10.1016/j.urology.2014.08.044.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Focal therapy in people with Prostate Cancer and Prostate Neoplasm, run by Radboud University Medical Center at 5 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lauren te Molder (+31243611111, Lauren.teMolder@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Oncological effectiveness (non-inferiority) defined as treatment failure (time frame: 36 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06223295, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2024.