Oligometastatic Prostate Cancer
Conditions
Keywords
prostate adenocarcinoma, oligometastases, radiotherapy, hypofractionation, brachytherapy
Brief summary
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.
Detailed 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.
Interventions
RADIATIONHypofractionated external beam radiotherapy
5500 cGy/20 fractions delivered 5 days per week over 4 weeks
RADIATIONHigh dose rate brachytherapy
A single fraction of 19 Gy is delivered from an automated afterloading Iridium-192 source via interstitial catheters placed under ultrasound guidance
RADIATIONPermanent seed implant
Iodine-125 radioactive seeds are implanted permanently in the prostate in a single procedure under transrectal ultrasound guidance
RADIATIONStereotactic body radiotherapy
External radiation using SABR technology delivers 36.25 Gy to the prostate in 5 fractions given either once weekly for 5 weeks or every second day over 2 weeks.
Sponsors
British Columbia Cancer Agency
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
There is one standard arm (5500/20) and 3 alternative arms. The alternative arms are selected at the treating center. Thus, each randomization is 2-way, but with a 3:1 weighting so that the 4 treatment arms have equal numbers of patients.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed study specific informed consent * European Cooperative Oncology Group performance status 0 to 2 * Histologically confirmed adenocarcinoma of the prostate * Any Tumor stage, any T, any N, M1 * No prior therapy for prostate cancer apart from androgen deprivation * Planned for long-term androgen deprivation therapy (greater than 9 months in duration) * Patient is able and willing to complete the quality of life questionnaires, and other assessments that are a part of this study * For brachytherapy arms, patient must be technically suitable for brachytherapy according to investigator, in terms of bladder function and prostate size.
Exclusion criteria
* High metastatic burden defined as 5 or more bone metastases or visceral metastases * Contraindications to EBRT such as active inflammatory bowel disease or previous pelvic radiation * For Brachytherapy Arms =: Any prior Transurethral resection of prostate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary symptoms | Baseline to 2 years | International Prostate Symptom score (0/35), higher worse |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Expanded Prostate Cancer Index (EPIC) urinary domain | Baseline to 2 years | Urinary Quality of life, 0/100 higher score better |
| EPIC bowel domain | Baseline to 2 years | Bowel quality of life, 0/100, higher score better. Series of validated questions concerning urgency, frequency, consistency, leakage, presence of blood and pain with bowel movements and then rates how big a problem each symptom was (0-5) |
| EPIC sexual domain | Baseline to 2 years | Sexual quality of life, 0/100, higher score better. Series of validated questions concerning frequency and quality of erections, presence of morning erections, ability to engage in sexual activity or intercourse, rates ability and then rates importance of each issue to the patient. |
| Biochemical failure (time to increase in prostate specific antigen (ng/ml) to 50% > nadir | Baseline to 3 years | Progression free survival measured as time to Prostate Specific Antigen (PSA) rise by 50% \> nadir |
| Distant metastatic failure | Baseline to 3 years | Progression free survival measured as time to new or progressive bone metastases |
| Nodal progression | Baseline to 3 years | Progression free survival measured as new or progressive adenopathy on imaging |
| Overall survival | 3 years | Overall survival regardless of cause of death |
| Cause specific survival | Within 3 years of treatment | Death from prostate cancer |
| Cost effectiveness | 3 years | Analysis of primary treatment costs and secondary treatment costs at time of progression |
Countries
Canada
Contacts
CONTACTJuanita Crook, MD
PRINCIPAL_INVESTIGATORJuanita Crook, MD
BCCancer
Outcome results
None listed