A Prospective Comparative Study of Outcomes With Proton and Photon Radiation in Prostate Cancer

Study Overview
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Brief Summary
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This study is a large, prospective, pragmatic, controlled comparison of patient-centric outcomes [quality of life (QOL), toxicity, and disease control] between parallel cohorts of men with prostate cancer treated simultaneously at proton therapy facilities and at geographically similar conventional (photon-based) radiation facilities using intensity-modulated radiation therapy (IMRT) techniques.

Detailed Description
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This study is a large, prospective, pragmatic, controlled comparison of patient-centric outcomes [quality of life (QOL), toxicity, and disease control] between parallel cohorts of men with prostate cancer treated simultaneously at proton therapy facilities and at geographically similar conventional (photon-based) radiation facilities using intensity-modulated radiation therapy (IMRT) techniques. This study includes a pre-specified randomized comparison of standard fractionation and moderate hypofractionation dose schemes within the proton therapy cohort. In addition, subgroup analyses will include a comparison of outcomes by race (Black vs. White), comorbidity score (0 vs. 1+), age (<65 vs. ≥65), fractionation schedule (standard, moderate, ultra-hypofractionation), and prostate cancer aggressiveness (very low and low, intermediate, and high risk) for all objectives. All interventions will be standard of care (SOC) radiation strategies using either IMRT or proton therapy. All patient-reported QOL, patient-scored and patient-reported toxicity, and disease control assessments will be SOC. Participants will also complete pretreatment surveys regarding demographic data, personal treatment goals, factors affecting treatment decision-making, and sources of information used in treatment selection.

Official Title
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A Prospective Comparative Study of Outcomes With Proton and Photon Radiation in Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Radiation: Standard of Care IMRT (Photon)
* Radiation: Standard of Care Proton Therapy
* Radiation: Proton Arm 1: Standard Proton Therapy
* Radiation: Proton Arm 2: Hypofractionated Proton Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of adenocarcinoma of the prostate. 30-85 years of age at the time of consent with a life expectancy estimation (LEE) of ≥ 8 years. Localized prostate cancer, as confirmed by staging with PSA, biopsy, Gleason score, DRE with or without mpMRI, and clinical stage. Very low-risk, low-risk, intermediate-risk, or high-risk disease based on NCCN Prostate Cancer Risk Group Guidelines and Joint AUA/ASTRO/SUO Guidelines. If patient has high-risk disease, nuclear medicine bone imaging must be performed to document the absence of overt metastatic disease in bones. ECOG/Zubrod Performance Status 0 - 2. Candidate for definitive prostate radiotherapy (either IMRT or proton). If patient is to be treated with IMRT, all treatment must be planned with IMRT; if patient is to be treated with protons, all treatment must be planned with protons (including pelvic nodes if treated). Exclusion Criteria: Findings of metastatic disease (nodal or distant, N1 or M1). Very high-risk prostate cancer based on NCCN Prostate Cancer Risk Group Guidelines and Joint AUA/ASTRO/SUO Guidelines. Prior procedures for treatment of prostate cancer, such as radical or robotic prostatectomy, high-intensity focused ultrasound, cryosurgery, or focal prostatectomy [note that procedures used for benign prostatic hyperplasia symptoms, such as transurethral resection of the prostate (TURP) and GreenLight Laser Therapy, are acceptable]. Previous prostate cancer treatment with the exception of ADT according to NCCN guidelines. History of invasive rectal malignancy or other malignancy in the true pelvis (e.g. bladder, rectum, or reproductive organs), regardless of disease-free interval. Active inflammatory bowel disease (i.e., patients requiring medical interventions or who are symptomatic). Prior pelvic RT for any reason. Documented lack of psychological ability or general health permitting completion of the study requirements and required follow-up. Documented diminished capacity to understand the risks and benefits of participation in research and to autonomously provide informed consent. In addition, because the embedded randomized controlled trial compares fractionation schemes, patients who are receiving pelvic node irradiation may not be enrolled on the randomized controlled trial.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 85 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: IMRT (Photon)<br>As this trial is pragmatic, all treatment will be standard of care. | Radiation: Standard of Care IMRT (Photon)<br>* As this trial is pragmatic, all treatment will be standard of care.<br>|
| Active Comparator: Proton Therapy Standard of Care<br>As this trial is pragmatic, all treatment will be standard of care. | Radiation: Standard of Care Proton Therapy<br>* As this trial is pragmatic, all treatment will be standard of care.<br>|
| Experimental: Standard Proton Therapy<br>78.0 Gy (RBE) in 39 fractions. This is Arm 1 of the embedded randomized trial. | Radiation: Proton Arm 1: Standard Proton Therapy<br>* 78.0 Gy (RBE) in 39 fractions<br>|
| Experimental: Hypofractionated Proton therapy<br>60.0 Gy (RBE) in 20 fractions This is Arm 2 of the embedded randomized trial. | Radiation: Proton Arm 2: Hypofractionated Proton Therapy<br>* 60.0 Gy (RBE) in 20 fractions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bowel urgency and bowel frequency Expanded Prostate Cancer Index Composite (EPIC) item scores | EPIC assesses the disease-specific aspects of prostate cancer and its therapies and comprises four summary domains (Urinary, Bowel, Sexual and Hormonal). Factor analysis supports dividing the Urinary Domain Summary Score into two distinct Incontinence and Irritative/Obstructive subscales. In addition, each Domain Summary Score has measurable Function Subscale and Bother Subscale components. Response options for each EPIC item form a Likert scale, and multi-item scale scores are components. Response options for each EPIC item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better HRQOL | 2-years after the end of radiation therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade 2 or higher toxicity for each adverse event assessed by CTCAE | The NCI Common Terminology Criteria for Adverse Events v5.0 is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. | 2-years after the end of radiation therapy | 
| Grade 2 or higher toxicity for each adverse event assessed by PRO-CTCAE. | PRO-CTCAE responses are scored from 0 to 4, and there are as yet no standardized scoring rules for how to combine attributes into a single score or how best to analyse PRO-CTCAE data longitudinally. PRO-CTCAE scores for each attribute (frequency, severity and/or interference) should be presented descriptively (e.g. summary statistics or graphical presentations). CTCAE grades for the corresponding time period should be presented in conjunction with PRO-CTCAE scores. | 2-years after the end of radiation therapy | 
| Freedom from biochemical progression using PSA results. | Biochemical failure is defined as a sustained rise in PSA of 2 ng/mL or more above the nadir (the lowest PSA level after radiotherapy). | 3-years after the end of radiation therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer, Proton Radiation, Photon Radiation, Cancer of the Prostate