Comparing the Side Effects of Low Dose Rate Brachytherapy Against Ultra-Hypofractionated Radiotherapy Using Spacer Gel Treatment in Men With Cambridge Prognostic Groups (CPG) 1 to 3 (NCCN Low to Intermediate Risk) Prostate Cancer
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 220
- 试验地点
- 1
- 主要终点
- EPIC-26 score minimally important difference
研究概览
简要总结
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.
详细描述
The hypothesis of the study is that treatment-related toxicity after Stereotactic Body Radiotherapy (SBRT) is not significantly different to that after Low Dose Rate (LDR) Brachytherapy. SBRT is an economically attractive strategy that is not invasive but requires multiple hospital visits (one visit per fraction, currently a minimum of 5 visits) whereas LDR Brachytherapy only requires one treatment visit. Both treatment options have independently shown excellent control of prostate cancer with low toxicity but high-quality evidence from a randomised controlled study with sufficient follow up on toxicity and efficiency comparing the two treatments is lacking.
Patients suitable for the trial will be highlighted at their local prostate cancer multidisciplinary team (MDT) at Royal Surrey County Hospital, Frimley Park Hospital, East Surrey Hospital & Ashford and St Peters Hospital (All hospitals are members of the Royal Surrey National Health Service (NHS)Trust). Patients deemed eligible for all radical treatment options for their prostate cancer (surgery or radiotherapy), will be reviewed by the surgical and oncology team as per standard of care management. Should the patient express an interest in radiation treatment and be willing to be randomised to either radiation treatment arm (LDR brachytherapy or SBRT) an onward referral should be made to the trial team at the Royal Surrey County Hospital. Written patient information on the trial can be provided to the patient before meeting the trial team. Should the patient have a preference for which treatment arm they favour, then they will be offered this as standard of care (if they be deemed suitable by the treating clinician). If patients are willing to have either LDR brachytherapy or SBRT treatment, then they will undergo screening at their first trial appointment.
All men within the trial will have a histological diagnosis of low to intermediate risk prostate cancer defined using National Institute for Health and Care Excellence (NICE) criteria. Those that meet the inclusion criteria as documented in the protocol summary will undergo a baseline urinary flow rate assessment, transrectal ultrasound, and International Prostate Symptom Score (IPSS) questionnaire to ensure they are candidates for the study. All of these screening tests will take place during their first trial appointment at the Stokes Centre for Urology at the Royal Surrey County Hospital. The urinary flow rate should be above 10ml / second, as a figure less than this is suggestive of an obstructive prostate, likely requiring intervention such as a transurethral resection of the prostate (TURP).
A transrectal ultrasound is an important diagnostic tool as it demonstrates the size and shape of the prostate. Men with a prostate gland larger than 60 cc, or those with a large median lobe are not good candidates for LDR brachytherapy and therefore are excluded from the trial, due to challenging dose distribution and increased risk of toxicity.
A Prostate Specific Antigen (PSA) within 60 days of randomisation is required to be used as a baseline result. Any patients deemed high risk and therefore requiring hormonal treatment, as per local policy, alongside their radiotherapy, will be excluded from the study. Patients not eligible for the trial, will be offered an alternative standard of care option and these patients will not be included in the final analysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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
- •PSA ≤ 20 ng/ml (please note if the treating clinician determines androgen deprivation therapy (ADT) is required this is an
排除标准
- •). A PSA must be available within 60 days of randomisation.
- •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.
- •Exclusion Criteria:
- •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.
研究组 & 干预措施
4D low dose rate brachytherapy
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).
干预措施: 4D Low Dose Rate Prostate Brachytherapy (Radiation)
Ultra-hypofractionated Radiotherapy
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).
干预措施: Ultra-hypofractionated Radiotherapy (Radiation)
结局指标
主要结局
EPIC-26 score minimally important difference
时间窗: 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.
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.
次要结局
- 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.)