Side Effects of Low Dose Rate Brachytherapy and Ultra-hypofractionated Radiotherapy in Low to Intermediate Risk Prostate Cancer

NCT07210502 | Not Yet Recruiting FDA Device

• 1 other identifier: LDR BURST Trial
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

The LDR BURST trial will compare the side effects of two radiotherapy treatments for men with localised prostate cancer. The first treatment is 4D low dose rate brachytherapy where small radioactive seeds are inserted into the prostate gland under ultrasound guidance. A computerised tomography scan is subsequently performed to check seed positioning. Patients usually return home the same day. The seeds emit their radiation over several months before losing their activity. Stereotactic radiotherapy, an alternative treatment, is a form of external radiation using precise high energy x-rays to target the prostate gland. It is delivered in 5 treatment sessions on alternate days; the full treatment course is completed within 2 weeks. Stereotactic radiotherapy has recently been approved by the National Health Service following successful results in international trials demonstrating it is safe and effective to give external radiotherapy in five treatment sessions. Delivering a higher dose in each treatment fraction is known as 'ultra-hypofractionation'. Before the treatment, men will undergo a minor procedure, typically under local anaesthetic, to have metallic markers inserted into the prostate to improve visibility of the prostate gland when planning and delivering the treatment. The side effects of both the radiation treatments are similar. Common side effects include bladder issues, such as needing to urinate more often and having a slower urine flow. Patients might also experience more frequent and looser bowel movements, occasionally with a little blood. Symptoms usually improve over time. Additionally, some men might have trouble achieving or maintaining an erection after radiation treatment, this can often be managed with medications. Both of the treatments use ionising radiation to destroy the prostate cancer cells which may cause cancer many years or decades after exposure. The chances of this happening are the same whether taking part in this trial or not. A protective gel, called Barrigel, will be inserted into the space between the prostate gland and the rectum increasing the distance between them. This significantly reduces the dose of radiation to the rectum. The gel can be inserted at the same time as the brachytherapy seed or fiducial marker insertion. The gel is slowly reabsorbed following treatment over the next 3 to 6 months. The trial will randomly assign 110 men to each radiation treatment to compare their side effects. There is a 50% chance the patient will be assigned to brachytherapy and 50% chance of stereotactic radiotherapy. Patients will be asked to complete four questionnaires prior to starting treatment and at regular time points following treatment. They will be telephoned every 4 weeks for the first 2 months to check on side effects, followed by a face-to-face appointment at 3 months, and a PSA blood test, and then followed up at regular intervals for 5 years.

Conditions

Prostate Adenocarcinoma

Keywords

low dose rate brachytherapy; Stereotactic Body Radiation Therapy; rectal spacer gel

Outcome Measures

Primary Outcomes (1)

• EPIC-26 score minimally important difference

  The EPIC-26 questionnaire is a preeminent tool extensively characterised to measure health-related quality of life in men with localised prostate cancer. Our study is powered to detect the minimally important differences in urinary, sexual, and bowel function domains relative to the pre-treatment values.

  Scores will be collected pre-treatment, 1, 2, 3, 6, 12, 18, and 24 months after treatment, and then yearly up to the 5-year post-treatment time point.

Secondary Outcomes (3)

• International Prostate Symptom Score (IPSS)

  Scores will be collected pre-treatment and at 1, 2, 3, 6, 12, 18, and 24 months after treatment, and then annually up to the 5-year post treatment time point.

• International Index of Erectile Function (IIEF-5)

  Scores will be collected pre-treatment and at 1, 2, 3, 6, 12, 18, and 24 months after treatment, and then annually up to the 5-year post treatment time point.

• Vaizey faecal inconticence score

  Scores will be collected pre-treatment and at 1, 2, 3, 6, 12, 18, and 24 months after treatment, and then annually up to the 5-year post treatment time point.

Other Outcomes (2)

• Prostate-Specific Antigen (PSA)

  Values will be collected pre-treatment, at 3 and 6 months post-treatment, and thereafter every 6 months up to the 5 years time point.

• Survival

  5 years post-treatment.

Study Arms (2)

4D low dose rate brachytherapy

ACTIVE COMPARATOR

Insertion of iodine -125 radioactive seeds in the prostate gland. Prescription dose 145 Gy. Permanent placement of seeds under general anaesthesia and real time image guidance. Post brachytherapy insertion of Barrigel (rectal space gel).

Radiation: 4D Low Dose Rate Prostate Brachytherapy

Ultra-hypofractionated Radiotherapy

ACTIVE COMPARATOR

Stereotactic Body Radiation Therapy (SBRT).Prescription dose 36.25 Gy given in 5 fractions over 1-2 weeks (i.e. daily or alternate daily) delivered on linear accelerator. All patients will have fiducial markers inserted prior to their treatment together with insertion of Barrigel (rectal space gel).

Radiation: Ultra-hypofractionated Radiotherapy

Interventions

4D Low Dose Rate Prostate Brachytherapy RADIATION

Permanent implantation of radioactive seeds in the prostate gland which slowly deposit half their dose approximately every 60 days. Prescription dose 145 Gy.

4D low dose rate brachytherapy

Ultra-hypofractionated Radiotherapy RADIATION

The prescription dose is 36.25 Gy given in 5 fractions over 1-2 weeks (i.e. daily or alternate daily at department discretion) delivered on linear accelerator

Ultra-hypofractionated Radiotherapy

Eligibility Criteria

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

You may qualify if:

• Men aged ≥18 years at randomisation
• The research subject must have capacity to sign a written informed consent document for the trial
• WHO performance status 0 - 2
• Gleason score 3+3 or 3+4

You may not qualify if:

• Clinical and/or MRI stage T1c -T2c, N0-X, M0-X
• Histological confirmation of prostate adenocarcinoma within the last 18 months (unless on active surveillance). Patients who were on active surveillance should have an up-to-date MRI within 8 weeks of the decision to treat to confirm organ confined disease.
• Previous malignancy within the last 2 years (except basal cell carcinoma or squamous cell carcinoma of the skin), or if previous malignancy is expected to significantly compromise 10-year survival.
• Patients under investigation for synchronous primary at time of randomisation
• Prior pelvic radiotherapy.
• Prior treatment with ADT or current need for ADT based on risk features
• Prostate cancer in greater than 50% of template biopsy cores or a significant maximum core length containing prostate cancer for which the treating clinician deems the patient would benefit from ADT
• Any prior active treatment for prostate cancer (patients previously on active surveillance are eligible if they meet all other eligibility criteria)
• Life expectancy \< 10 years Men with a prostate gland larger than 60 cc, or those with a large median lobe• Hip prostheses or any other implants/hardware that introduce substantial CT artefacts making it challenging to delineate the target or organs at risk. This is to be assessed on a case-by-case basis with the available staging imaging.
• Medical conditions likely to make radiotherapy inadvisable e.g. inflammatory bowel disease, significant urinary symptoms.
• International Prostate Symptom Score (IPSS) \> 15 points
• Anticoagulation with warfarin/ bleeding tendency making fiducial placement, spacer gel insertion or brachytherapy unsafe in the opinion of the clinician
• Contraindications for Barrigel insertion such as previous documented allergic reaction to gel, previous rectal surgery or known rectal fistula.
• Participation in another concurrent treatment protocol for prostate cancer.

Sponsors & Collaborators

• Royal Surrey County Hospital NHS Foundation Trust: lead

Study Sites (1)

Royal Surrey NHS Foundation Trust

Guildford, Surrey, GU2 7XX, United Kingdom

Location

Related Publications (6)

• Vaizey CJ, Carapeti E, Cahill JA, Kamm MA. Prospective comparison of faecal incontinence grading systems. Gut. 1999 Jan;44(1):77-80. doi: 10.1136/gut.44.1.77.

  PMID: 9862829 BACKGROUND

• Mariados NF, Orio PF 3rd, Schiffman Z, Van TJ, Engelman A, Nurani R, Kurtzman SM, Lopez E, Chao M, Boike TP, Martinez AA, Gejerman G, Lederer J, Sylvester JE, Bell G, Rivera D, Shore N, Miller K, Sinayuk B, Steinberg ML, Low DA, Kishan AU, King MT. Hyaluronic Acid Spacer for Hypofractionated Prostate Radiation Therapy: A Randomized Clinical Trial. JAMA Oncol. 2023 Apr 1;9(4):511-518. doi: 10.1001/jamaoncol.2022.7592.

  PMID: 36757690 BACKGROUND

• Langley SE, Laing RW. 4D Brachytherapy, a novel real-time prostate brachytherapy technique using stranded and loose seeds. BJU Int. 2012 Feb;109 Suppl 1:1-6. doi: 10.1111/j.1464-410X.2011.10824.x.

  PMID: 22239223 BACKGROUND

• Alexander SE, Kinsella J, McNair HA, Tree AC. National survey of fiducial marker insertion for prostate image guided radiotherapy. Radiography (Lond). 2018 Nov;24(4):275-282. doi: 10.1016/j.radi.2018.06.003. Epub 2018 Jul 7.

  PMID: 30292494 BACKGROUND

• Tree AC, Ostler P, van der Voet H, Chu W, Loblaw A, Ford D, Tolan S, Jain S, Martin A, Staffurth J, Armstrong J, Camilleri P, Kancherla K, Frew J, Chan A, Dayes IS, Duffton A, Brand DH, Henderson D, Morrison K, Brown S, Pugh J, Burnett S, Mahmud M, Hinder V, Naismith O, Hall E, van As N; PACE Trial Investigators. Intensity-modulated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): 2-year toxicity results from an open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2022 Oct;23(10):1308-1320. doi: 10.1016/S1470-2045(22)00517-4. Epub 2022 Sep 13.

  PMID: 36113498 BACKGROUND

• van As N, Yasar B, Griffin C, Patel J, Tree AC, Ostler P, van der Voet H, Ford D, Tolan S, Wells P, Mahmood R, Winkler M, Chan A, Thompson A, Ogden C, Naismith O, Pugh J, Manning G, Brown S, Burnett S, Hall E. Radical Prostatectomy Versus Stereotactic Radiotherapy for Clinically Localised Prostate Cancer: Results of the PACE-A Randomised Trial. Eur Urol. 2024 Dec;86(6):566-576. doi: 10.1016/j.eururo.2024.08.030. Epub 2024 Sep 11.

  PMID: 39266383 BACKGROUND

Related Links

• NICE Prostate cancer: diagnosis and treatment
• 4D Brachytherapy practical guide
• IPSS questionnaire
• IIEF-5/SHIM questionnaire

Study Officials

• Stephen E Langley, Professor of Urology

  Royal Surrey NHS Foundation Trust

  STUDY CHAIR

Central Study Contacts

William Hayhurst, Doctor

CONTACT

+(44)1483 571122; william.hayhurst@nhs.net

Carla Perna, Docter

CONTACT

+(44)1483 571122; carla.perna@nhs.net

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: June 30, 2025
• First Posted: October 7, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: October 7, 2025

Record last verified: 2025-09

Locations

GB (1)