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

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. Pre-specified subset comparators
include a randomized comparison of standard fractionation and moderate hypofractionation dose
schemes within the proton therapy cohort. In addition, analysis of heterogeneous treatment
effects (HTE) will include a comparison of outcomes by race (Black vs. White), comorbidity
score (0 vs. 1+), age (≤65 vs. >65), and prostate cancer aggressiveness (low, intermediate,
and high risk) for all endpoints.

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.

Inclusion Criteria:

- Diagnosis of adenocarcinoma of the prostate.

- Localized prostate cancer, as confirmed by staging with PSA, biopsy, Gleason score,
DRE, and clinical stage.

- Low-risk, intermediate-risk, or high-risk disease based on NCCN Prostate Cancer Risk
Group Guidelines1 and Joint AUA/ASTRO/SUO Guidelines.51

- If patient has high-risk disease, nuclear medicine bone imaging must be performed to
document the absence of overt metastatic disease in bones.

- 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).

- No previous prostate cancer treatment with the exception of short-term (≤6 months) ADT
according to NCCN guidelines.

- 30-80 years of age at the time of consent with a life expectancy estimation (LEE) of
≥10 years.

- ECOG/Zubrod Performance Status 0 - 2.

Exclusion Criteria:

- Findings of metastatic disease (nodal or distant, N1 or M1).

- Very low-risk or very high-risk prostate cancer based on NCCN Prostate Cancer Risk
Group Guidelines1 and Joint AUA/ASTRO/SUO Guidelines.51

- Prior prostate surgical procedure, including transurethral resection of the prostate
(TURP) and GreenLight Laser Therapy.

- History of invasive rectal malignancy or other pelvic malignancy, regardless of
disease-free interval.

- Active inflammatory bowel disease (i.e., patients requiring medical interventions or
who are symptomatic) or documented history of inflammatory bowel disease requiring
intervention.

- 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.