Effectiveness of Focal Therapy in Men With Prostate Cancer

NCT06223295 | Recruiting DMC

• 1 other identifier: 2023-16261
• Study Type: interventional
• Target: 356
• Locations: 1 country
• Sites: 5

Brief 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. 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.

Conditions

Prostate Cancer; Prostate Neoplasm

Keywords

prostate neoplasm; focal therapy; prostate cancer

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  12 months

Secondary Outcomes (15)

• Metastasis-free survival

  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

  at baseline, 3, 6, 12, 24, 36, 48 and 60 months

• Health-related quality of life using the International Consultation on Incontinence Questionnaire

  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

  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

  at baseline, 3, 6, 12, 24, 36, 48 and 60 months

Study Arms (2)

Focal therapy

ACTIVE COMPARATOR

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

Procedure: Focal therapy

Usual care

ACTIVE COMPARATOR

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

Procedure: Usual care

Interventions

Focal therapy 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

Also known as: TULSA, IRE, Hifu

Focal therapy

Usual care PROCEDURE

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

Also known as: Radical prostatectomy, Radiotherapy

Usual care

Eligibility Criteria

• Age: 45 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Isala: collaborator
• Amsterdam UMC, location VUmc: collaborator
• St. Antionius Hospital: collaborator
• Hifu kliniek: collaborator
• Dutch National Health Care Institute: collaborator
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator
• Nederlandse Vereniging voor Radiotherapie en Oncologie: collaborator
• Wetenschapscommissie interventieradiologie/Nederlandse vereniging voor interventieradiologie: collaborator
• Inspire2live: collaborator
• Prostaatkankerstichting: collaborator
• Nederlandse Vereniging voor Urologie: collaborator

Study Sites (5)

Radboud University Medical Centre

Nijmegen, Gelderland, 6525GA, Netherlands

RECRUITING

Hifu kliniek

Etten-Leur, North Brabant, Netherlands

NOT YET RECRUITING

Amsterdam UMC

Amsterdam, North Holland, Netherlands

NOT YET RECRUITING

Isala klinieken

Zwolle, Overijssel, Netherlands

NOT YET RECRUITING

St. Antonius hospital

Nieuwegein, Utrecht, Netherlands

NOT YET RECRUITING

Related Publications (14)

• 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.

  PMID: 25770484 BACKGROUND

• 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.

  PMID: 34489140 BACKGROUND

• de 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.

  PMID: 23860533 BACKGROUND

• 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.

  PMID: 31967521 BACKGROUND

• Blazevski 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.

  PMID: 31103721 BACKGROUND

• 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.

  PMID: 26777228 BACKGROUND

• Bonekamp 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.

  PMID: 29943185 BACKGROUND

• Ramsay 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.

  PMID: 27545572 BACKGROUND

• 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.

  PMID: 31412013 BACKGROUND

• 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.

  PMID: 34740477 BACKGROUND

• Gharzai 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.

  PMID: 33662287 BACKGROUND

• Skolarus 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.

  PMID: 25530370 BACKGROUND

• Tay 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.

  PMID: 28349978 BACKGROUND

• Cella 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.

  PMID: 18647260 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

High-Intensity Focused Ultrasound Ablation; Radiotherapy

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Ultrasonic Therapy; Diathermy; Hyperthermia, Induced; Therapeutics; Ablation Techniques; Surgical Procedures, Operative

Central Study Contacts

Lauren te Molder

CONTACT

+31243611111; Lauren.teMolder@radboudumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2023
• First Posted: January 25, 2024
• Study Start: February 1, 2024
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): February 1, 2031
• Last Updated: February 20, 2024

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (5)