A Study To Evaluate Hypofractionated Proton Therapy Or IMRT For Recurrent, Oligometastatic Prostate Cancer

PRIMARY OBJECTIVE:

I. To assess late >= grade 3 gastrointestinal (GI) and/or genitourinary (GU) toxicity of interest within each treatment arm, moderate hypofractionation (MHF) and conventional fractionation (CF), delivered with PBRT or IMRT (late defined as 3 to 24 months after protocol radiation therapy \[RT\]).

SECONDARY OBJECTIVES:

I. Late grade >= 2 GI and/or GU toxicities of interest within 24 months after protocol treatment, using Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0.

II. Acute grade >= 3 GI and/or GU toxicities of interest during and within 3 months after the protocol treatment, using CTCAE v4.0.

III. Compare the rates of late >= grade 3 GI and/or GU toxicity between the 2 treatment schedules.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo IMRT or PBRT 5 days a week over 3 weeks. Patients undergo positron emission tomography (PET) scan, computed tomography (CT) scan, magnetic resonance imaging (MRI), and blood sample collection throughout the study.

ARM II: Patients undergo IMRT or PBRT 5 days a week over 5 weeks. Patients undergo PET scan, CT scan, MRI, and blood sample collection throughout the study.

After completion of study, patients are followed up at 3-6, 12, 18, 24, 30, 36, 42, 48, 54, and 60 months.

• Intensity-Modulated Radiation Therapy (Radiation), also known as IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy: Undergo IMRT
• Proton Beam Radiation Therapy (Radiation), also known as PBRT, Proton, Proton EBRT, Proton External Beam Radiotherapy, Proton Radiation Therapy, Radiation, Proton Beam, External beam radiation therapy protons (procedure), emission tomography (procedure), positron emission tomography scan, Positron-Emission Tomography, PT: Undergo proton beam radiation therapy
• Quality-of-Life Assessment (Other), also known as Quality of Life Assessment: Ancillary studies
• Questionnaire Administration (Other): Ancillary studies
• Computed Tomography (Procedure), also known as CAT, CAT Scan, Computed Axial Tomography, computerized axial tomography, Computerized axial tomography (procedure), Computerized Tomography (CT) scan, computerized tomography, CT, CT SCAN, tomography: Undergo CT scan
• Magnetic Resonance Imaging (Procedure), also known as Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging (MRI) Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, nuclear magnetic resonance imaging, Structural MRI, sMRI: Undergo MRI
• Biospecimen Collection (Procedure), also known as Biospecimen Collected, Specimen Collection, Biological Sample Collection, Sample Collection: Undergo blood sample collection

Primary outcomes

• Incidence of Late Grade 3 or Higher GI and/or GU Toxicity [24 months]: Assessed by the percent of patients who experience a late (≥ 90 days after RT start date) grade 3 or higher gastrointestinal (GI) and/or genitourinary (GU) adverse event (AE) defined as possibly, probably, or definitely related to radiation therapy (RT). Adverse events will be graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Secondary outcomes

• Incidence of Acute Adverse Events [3 months]: Assessed by the percent of patients with >= grade 3 GI or GU acute adverse events. Acute AEs are defined as those that occur from day 1, or commencement of RT, through 3 months after the completion of protocol treatment.
• Incidence of Late Adverse Events [Between 3 months and 2 years after completion of proton beam therapy]: Assessed by the number of ≥ grade 2 GI or GU late adverse events per CTCAE v 4.0 will be recorded. A late AE is defined as an adverse event that occurs any time between 3 months and 2 years after completion of protocol treatment.
• Incidence of Grade 3 or Higher GI or GU Adverse Events Per Treatment Schedule [Up to 60 months]: Assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Rates of late ≥ grade 3 GI and/or GU toxicity will be compared between the treatment schedules.
• Incidence of Adverse Events [Up to 60 months]: Assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The maximum grade for each type of adverse event will be recorded for each patient.

Other outcomes

• Expanded Prostate Cancer Index Composite Short Form (EPIC-26) Questionnaire [Baseline, up to 60 months]: The EPIC-26 questionnaire is a 26-item questionnaire used to assess health-related quality of life (HRQOL). Items are scores on a Likert-type scales such as 0-4 where 0=no problem and 4=big problem. Higher scores indicate better HRQOL.
• Disease-free Survival [Up to 60 months]: Defined as the time from registration until the time of the first occurrence of biochemical failure, local recurrence, regional recurrence, distant metastases, or death due to any cause
• Disease-specific Mortality [Up to 60 months]: Defined as the time from registration until death due to prostate cancer (death attributed to carcinoma of the prostate by the investigator or death due to complications of treatment). The distribution of disease-specific mortality will be estimated using the cumulative incidence function, with death from other causes as the competing event.
• Overall Survival [Up to 60 months]: Defined as the time from registration until death due to any cause

Sex: Male, ages: 18 Years to any

Inclusion Criteria:

* Male; age >= 18 years
* Histological confirmation of prostate adenocarcinoma
* Recurrent prostate cancer after prior receipt of primary radiotherapy to the prostate \[can also include treatment of seminal vesicles (SVs) and lymph nodes (LNs)\] or salvage RT to the prostate fossa (can also include prior pelvic RT)
* Oligometastatic extent of disease

  * Recurrent disease involving lymph nodes as diagnosed with choline positron emission tomography (PET)/computed tomography (CT) or other advanced PET imaging \[prostate-specific membrane antigen (PSMA) or flucyclovine\]
  * Limited to pelvic and/or retroperitoneal/para-aortic lymph nodes
* Zubrod performance score (PS) =< 1
* Signed informed consent

Exclusion Criteria:

* Bone or visceral metastases present at the time of treatment (consolidative radiotherapy allowed)
* Lymph node metastases beyond the pelvis and/or retroperitoneum
* Contraindications to RT (e.g., uncontrolled inflammatory bowel disease)
* Contraindications to androgen suppression
* Concurrent cytotoxic chemotherapy
* Previous or concurrent malignancy other than non-melanoma skin cancer within 5 years of diagnosis of prostate cancer
* Inability to start the radiation portion of the protocol treatment within 6 months after study enrollment
* Medical or psychiatric conditions that preclude informed decision-making or compliance with the protocol treatment or follow-up

Participant flow

Outcome results

• Incidence of Late Grade 3 or Higher GI and/or GU Toxicity (Primary), Number, percent of participants: Arm I (Moderate Hypofractionation) 5.7 (1.6 to 14); Arm II (Conventional Fractionation) 0 (0 to 10.1)
• Incidence of Acute Adverse Events (Secondary), Number, percent of patients: Arm I (Moderate Hypofractionation) 0 (0 to 5.5); Arm II (Conventional Fractionation) 0 (0 to 10.1)
• Incidence of Late Adverse Events (Secondary)
• Incidence of Grade 3 or Higher GI or GU Adverse Events Per Treatment Schedule (Secondary)
• Incidence of Adverse Events (Secondary)
• Expanded Prostate Cancer Index Composite Short Form (EPIC-26) Questionnaire (Other pre specified)
• Disease-free Survival (Other pre specified)
• Disease-specific Mortality (Other pre specified)
• Overall Survival (Other pre specified)

Adverse events

Time frame: 24 months

Serious adverse events by term

Other adverse events by term

• Study Protocol and Statistical Analysis Plan (PDF, 2026-04-24)
• Informed Consent Form (PDF, 2022-11-30)

• Brian J. Davis, M.D., Principal investigator, Mayo Clinic in Rochester