Daily Adaptive Radiation Therapy Using an Individualized Approach for Prostate Cancer

Study Overview
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Brief Summary
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This trial is a prospective, single-arm, multi-center clinical trial designed to assess whether adaptive radiotherapy with urethral sparing for low to intermediate risk localized prostate cancer will translate into a decreased rate of patient reported acute urinary side effects, as measured by the patient reported EPIC-26 questionnaire, compared with the historically reported rate for non-adaptive, non-urethral sparing prostate SBRT.

Official Title
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Daily Adaptive Stereotactic Body Radiation Therapy for Prostate Cancer With Urethral Sparing: A Prospective Trial Using an Individualized Approach to Reduce Urinary Toxicity

Conditions
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Prostate Cancer

Intervention / Treatment
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* Device: Daily adaptive SBRT with urethral sparing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has NCCN low or intermediate risk prostate cancer that is biopsy proven. Prostate volume is ≤80cc as assessed by MRI prior to radiotherapy. AUA/IPSS score is ≤ 15. ECOG performance status is ≤2 (or Karnofsky score is ≥60%). Patient has no PIRADS 4 or 5 lesion on prostate MRI contacting the urethra (determined at physician discretion). Patient has the ability to complete required patient questionnaires. Patient age ≥ 18 years (or greater than the local age of majority). Patient has the ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Patient has baseline grade ≥3 GI or GU toxicity Patient has had prior overlapping pelvic radiotherapy. Patient has had prior transurethral resection of the prostate, prostate HIFU, or cryoablation. Patient has node positive prostate cancer. Patient has extracapsular extension (capsular abutment is permitted). Patient has active inflammatory bowel disease or active collagen vascular disease. Patient cannot undergo prostate MRI. Patient cannot undergo prostate fiducial marker placement. Patient has ongoing receipt of cytotoxic chemotherapy (androgen deprivation therapy is allowed).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adaptive SBRT with Urethral Sparing<br>Daily adaptive stereotactic body radiation therapy delivering 40 Gy in 5 fractions to the prostate while delivery 35-36 Gy in 5 fractions to the urethra. | Device: Daily adaptive SBRT with urethral sparing<br>* The radiation plan for each daily fraction is adapted from the initial plan based on cone beam CT imaging acquired while the participant is laying on the treatment machine.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient-reported acute urinary toxicity | Minimum clinically important change (MCIC) status in patient-reported urinary QOL, as determined by the worst change reported by each subject in their EPIC-26 urinary domain scores. | 90 days after end of SBRT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from biochemical recurrence | Rate of biochemical recurrence free survival, as determined by the Phoenix definition (PSA level of 2 ng/ml or more higher than the lowest post-SBRT value) | 5 years after end of SBRT | 
| Patient-reported quality of life issues related to prostate cancer. | Patient-reported quality of life changes during and after adaptive prostate SBRT treatment using the Expanded Prostate Cancer Index Composite Short Form (EPIC-26) questionnaire. | Baseline; during treatment; 6 weeks, 3 months, 6 months, 12 months, 18 months, 2 years, 3 years, 4 years, and 5 years after end of SBRT | 
| Patient-reported erectile dysfunction symptoms | Patient-reported erectile dysfunction symptoms before, during and after adaptive prostate SBRT treatment using the Sexual Health Inventory for Men (SHIM) questionnaire. | Baseline; during treatment; 6 weeks, 3 months, 6 months, 12 months, 18 months, 2 years, 3 years, 4 years, and 5 years after end of SBRT | 
| Patient-reported urinary symptoms | Patient-reported urinary symptoms before, during and after adaptive prostate SBRT treatment using the International Prostate Symptom Score (IPSS) questionnaire. | Baseline; during treatment; 6 weeks, 3 months, 6 months, 12 months, 18 months, 2 years, 3 years, 4 years, and 5 years after end of SBRT | 
| Patient-reported overall quality of life | Patient-reported overall quality of life before, during and after adaptive prostate SBRT treatment using the EQ-5D-5L questionnaire. | Baseline; during treatment; 6 weeks, 3 months, 6 months, 12 months, 18 months, 2 years, 3 years, 4 years, and 5 years after end of SBRT | 
| Physician-reported toxicities | Physician-reported CTCAE v 5.0 adverse events | During treatment; 6 weeks, 3 months, 6 months, 12 months, 18 months, 2 years, 3 years, 4 years, and 5 years after end of SBRT | 
| Alpha-blocker medication use | Change in use of alpha-blocker medications for urinary symptoms | Baseline; during treatment; 6 weeks, 3 months, 6 months, 12 months, 18 months, 2 years, 3 years, 4 years, and 5 years after end of SBRT | 
| Metastasis-free survival | Metastasis-free survival | 5 years after end of SBRT | 
| Prostate-cancer specific mortality | Prostate-cancer specific mortality | 5 years after end of SBRT | 
| Overall survival | Overall survival | 5 years after end of SBRT | 
| Workflow metrics of adaptive SBRT for prostate cancer | Includes the time on table and frequency of using the adapted vs. non-adapted treatment plan for each fraction. | 2 weeks after start of SBRT | 
| Target and OAR dosimetry | Improvement in target coverage and/or reduction in dose to critical organs at risk in the adapted plan compared to the non-adaptive planned dosimetry | 2 weeks after start of SBRT | 
| Impact of rectal spacers | Physician reported toxicity and patient reported outcomes with or without implanted resorbable rectal spacer | Enrollment through 5 year follow up |