Prostate Cancer
Conditions
Keywords
Prostatic Neoplasms, Radiotherapy, Hypofractionation, Low Risk Prostate Cancer
Brief summary
The purpose of this study is to determine the safety and efficacy of a short course of radiotherapy (35 Gy / 5 fractions / 29 days) for the treatment of low-risk prostate cancer.
Detailed description
Rationale for Proposed Study With the availability of intensity modulated radiotherapy (IMRT) at the Odette Cancer Centre (OCC), there is an opportunity to explore the use of a much more intensive hypofractionation schedule for prostate cancer. Using an alpha/beta ratio of 1.3, a dose of 35 Gy in 5 fractions would be equivalent to 88 Gy delivered in 2 Gy fractions. For normal tissues (alpha/beta value of 2), this would be equivalent to 78 Gy in 2 Gy fractions. As such, the linear quadratic equation predicts that 35 Gy in 5 fractions should not result in any increased late toxicity for normal tissues compared to standard dose escalated radiotherapy. However, the biological dose to the prostate cancer would be significantly increased. As a safety precaution for this study proposal, the investigators propose to deliver 35 Gy in 5 fractions over 5 weeks (one radiotherapy fraction of 7 Gy per week) to allow for normal tissue repair. With IMRT, it is expected that there will be superior conformality of the high dose region around the target volume. As well, the use of daily on-line imaging will allow us to eliminate interfraction prostate motion errors and use tighter planning target volume margins for any residual intrafraction motion. At OCC, such an approach has already been shown to be feasible and is currently employed in the phase 1/2 concomitant boost study for high risk prostate cancer. If proven to be safe and effective, such a hypofractionated radiotherapy schedule may have significant practical advantages as well. With only 1 fraction of radiotherapy delivered each week (for a total of 5 weeks), there are huge savings in resource utilization and increased convenience for patients. The investigators propose to start a small phase 1 study to explore the use of this dose fractionation for men with low risk prostate cancer. The primary endpoint for this small pilot study would be acute and late normal tissue toxicities. If proven to be feasible and safe, external peer-reviewed funding will be sought to further explore this novel treatment schedule in a larger phase 2 setting.
Interventions
35Gy/5 fractions/29 days
Sponsors
Canadian Association of Radiation Oncology
Sunnybrook Health Sciences Centre
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Informed consent signed (Appendix A) * Adult men greater than 18 years of age * Histologically confirmed diagnosis of adenocarcinoma of the prostate (centrally reviewed). * Clinical stage T1-T2b, Gleason Score \< 6, and PSA \< 10 ng/mL * Less than 50% of biopsy cores +ve for cancer * Less than 50% overall surface area involved with cancer * Neoadjuvant hormone suppression therapy is allowed. However, PSA, must have been performed within 2 months of starting androgen suppression therapy. If androgen suppression therapy has been started LHRH agonist must be continued for a minimum of 3 months before initiation of gold fiducial marker insertion & radiotherapy planning.
Exclusion criteria
* Prior pelvic radiotherapy. * Concurrent anticoagulation medication (if it is unsafe to discontinue for gold seed insertion) * Diagnosis of bleeding diathesis * Presence of a hip prosthesis * Pelvic girth \>40cm (to ensure visibility of gold seeds on electronic portal imaging device) * Large prostate (\> 60 cm3) on imaging * Severe lower urinary tract symptoms (International Prostate Symptom Score \> 15 or nocturia \> 3)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Grade 3+ Gastrointestinal Toxicity | Acute period (up to 6 months) | Common Terminology Criteria for Adverse Events (CTCAE) v3.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Grade 3+ Genitourinary Toxicity | Acute (up to 6 months) and Late (6 months and after) | Common Terminology Criteria for Adverse Events (CTCAE) v3.0 |
| Incidence of Grade 3+ Rectal and Urinary Toxicity | Late (6 months and after) | Common Terminology Criteria for Adverse Events (CTCAE) v3.0 |
| Patient Reported Quality of Life | up to 5 years | Expanded Prostate Cancer Index Composite (EPIC) |
| Biochemical (ie. Prostate Specific Antigen) Disease Free Survival | 5 year | Failure = Follow-up PSA greater than nadir PSA + 2 ng/ml |
| Biopsy Positive Rate | 3 year | Patients were biopsied at 3 years post treatment |
Countries
Canada
Participant flow
Recruitment details
Patients were prospectively recruited from the Odette Cancer Centre from Oct 2006 to July 2008.
Participants by arm
| Arm | Count |
|---|---|
| All Patients Inclusion criteria were men over 18 years of age with histologically confirmed diagnosis of adenocarcinoma of the prostate. Only patients with clinical stage T1-T2b (TNM 2002) \[18\] Gleason Sum 66 and PSA 610 ng/ml were eligible. Neoadjuvant androgen deprivation therapy (ADT) was allowed for cytoreduction. Patients were excluded if they had prior pelvic radiation therapy, a bleeding diathesis which precluded safe gold seed insertion, the presence of hip prosthesis or pelvic girth \>40 cm. Lastly, prostate size \>90cm3 on imaging or severe lower urinary tract symptoms (IPSS \> 19) | 84 |
| Total | 84 |
Baseline characteristics
| Characteristic | All Patients | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 44 Participants | — |
| Age, Categorical Between 18 and 65 years | 40 Participants | — |
| Age, Continuous | 67 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Canada | 84 participants | — |
| Sex: Female, Male Female | 0 Participants | — |
| Sex: Female, Male Male | 84 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 34 / 84 |
| serious Total, serious adverse events | 2 / 84 |
Outcome results
Primary
Incidence of Grade 3+ Gastrointestinal Toxicity
Common Terminology Criteria for Adverse Events (CTCAE) v3.0
Time frame: Acute period (up to 6 months)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hypofractionated Radiation | Incidence of Grade 3+ Gastrointestinal Toxicity | 0 participants |
Secondary
Biochemical (ie. Prostate Specific Antigen) Disease Free Survival
Failure = Follow-up PSA greater than nadir PSA + 2 ng/ml
Time frame: 5 year
Population: low risk prostate cancer patients treated with SABR 35 Gy in 5 fractions over 29 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hypofractionated Radiation | Biochemical (ie. Prostate Specific Antigen) Disease Free Survival | 96 percent |
Secondary
Biopsy Positive Rate
Patients were biopsied at 3 years post treatment
Time frame: 3 year
Population: low risk prostate cancer patients treated with SABR 35 Gy in 5 fractions over 29 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hypofractionated Radiation | Biopsy Positive Rate | 3 Participants |
Secondary
Incidence of Grade 3+ Genitourinary Toxicity
Common Terminology Criteria for Adverse Events (CTCAE) v3.0
Time frame: Acute (up to 6 months) and Late (6 months and after)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hypofractionated Radiation | Incidence of Grade 3+ Genitourinary Toxicity | 1 Participants |
Secondary
Incidence of Grade 3+ Rectal and Urinary Toxicity
Common Terminology Criteria for Adverse Events (CTCAE) v3.0
Time frame: Late (6 months and after)
Population: low risk prostate cancer patients were treated with SABR 35Gy in 5 fractions over 29 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Hypofractionated Radiation | Incidence of Grade 3+ Rectal and Urinary Toxicity | Acute GU grade 3+ toxicity | 1 participants |
| Hypofractionated Radiation | Incidence of Grade 3+ Rectal and Urinary Toxicity | Acute GI grade 3+ toxicity | 0 participants |
| Hypofractionated Radiation | Incidence of Grade 3+ Rectal and Urinary Toxicity | Late GU grade 3+ toxicity | 0 participants |
| Hypofractionated Radiation | Incidence of Grade 3+ Rectal and Urinary Toxicity | Late GI grade 3+ toxicity | 1 participants |
Secondary
Patient Reported Quality of Life
Expanded Prostate Cancer Index Composite (EPIC)
Time frame: up to 5 years
Population: Patients were low risk prostate cancer patients treated with SABR 35Gy in 5 fractions over 29 days.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Hypofractionated Radiation | Patient Reported Quality of Life | Bowel quality of life change | 22 percentage with change in QOL |
| Hypofractionated Radiation | Patient Reported Quality of Life | Bladder quality of life change | 16 percentage with change in QOL |
| Hypofractionated Radiation | Patient Reported Quality of Life | Sexual quality of life change | 33 percentage with change in QOL |