Overview
We will investigate whether ultrahypofractionation using stereotactic ablative radiotherapy (SABR) or brachytherapy is as well-tolerated as moderately hypofractionated external beam radiotherapy (EBRT) for treating the prostate in patients with oligometastatic prostate cancer. Secondary aims include assessment of progression-free survival (PFS) and overall survival (OS) as well as cost-effectiveness. We hypothesize that ultrahypofractionation will maintain favorable toxicity profiles and quality of life while achieving comparable or better efficacy, thereby providing a convenient and cost-effective alternative to moderately hypofractionated EBRT.
Description
Men newly diagnosed with low volume oligometastatic prostate cancer defined as fewer than 5 bone metastases and/or non regional lymph node involvement who agree to treatment of the primary cancer with radiation will be randomized between standard moderately hypofractionated external radiotherapy (5500 centiGray/20 fractions as per Stampede trial) and one of 3 alternatives: stereotactic body radiotherapy (SABR) to deliver 36 Gy/5 fractions, or low dose rate Iodine 125 permanent seed implant or a single high dose rate temporary implant. The trial will take place in 4 regional cancer centers of British Columbia Cancer Agency, with each center choosing their preferred alternative to 5500/20. To achieve 4 equally sized treatment arms, each randomization is weighted 3:1 for 42 patients in each arm and 168 total accrual. The primary endpoint is urinary quality of life as assessed by the International Prostate Symptom Score (IPSS) . As the typical acute symptoms from each of these radiation modalities has a unique time course, assessments are done at 6 different points during the first 2 years. Secondary endpoints are global quality of life as assessed by Expanded Prostate Cancer Index (EPIC) urinary, bowel and sexual scores, progression free survival, overall survival and cost effectiveness.
Eligibility
Inclusion Criteria:
- Able to provide informed consent
- European Cooperative Oncology Group performance status 0 to 2
- Medically fit for all protocol treatment and follow-up
- Histologically confirmed adenocarcinoma of the prostate
- Newly diagnosed any Tumor stage, any Nodal stage but with oligo metastases
- No prior therapy for prostate cancer apart from androgen deprivation
- Luteinizing Hormone Releasing Hormone (LHRH) agonists or antagonists must have started within 24 weeks of randomization
- If used, anti-androgens must have started within 26 weeks of randomization
- Able to complete the necessary investigations prior to and within 12 weeks of starting Androgen Deprivation Therapy (ADT) or of randomization (History and physical examination, PSA)
- Able to complete the necessary investigations priOr to start of Radiotherapy (Transrectal ultrasound-guided biopsy, CT chest, abdomen & pelvis or MRI abdomen and pelvis, and Bone scan)
- Planned for long-term androgen deprivation therapy
Exclusion Criteria:
- High metastatic burden defined as 5 or more bone metastases or visceral metastases
- Abnormal liver function
- Contraindications to EBRT such as active inflammatory bowel disease or previous pelvic radiation
- Medically unfit for anesthesia
- International Prostate Symptom Score (IPSS) greater than 20
- Restrictive flow pattern with peak flow rate less than10 mL per second or post-void residual greater than 25 per cent of voided volume (when uroflowmetry available)
- Prostate volume greater than 60cc after maximal cytoreduction
- Pubic arch interference
- Transurethral resection of prostate (TURP) within 12 weeks of brachytherapy