PSMA-PET Guided De-escalation of Salvage Radiation Treatment in Recurrent Prostate Cancer

PSMA-PET Guided De-escalation of Salvage Radiation Treatment in Patients With Recurrent Prostate Cancer After Prostatectomy

Purpose: Prospective, single-site Phase II study testing whether PSMA-PET/MRI-guided, de-escalated salvage radiation reduces acute Grade ≥2 toxicity versus a 44% historical rate, while maintaining cancer control after prostatectomy.Population/Eligibility: Adult men ≥30 years with prior radical prostatectomy and biochemical persistence/recurrence per NCCN (persistent positive PSA after RP, or undetectable PSA that becomes detectable and rises on ≥2 determinations, or PSA >0.1 ng/mL). Must have a targetable PSMA-avid lesion in the prostate bed and/or pelvic lymph nodes and/or an MRI-defined lesion suspicious for local recurrence. KPS ≥80 or ECOG ≤2; life expectancy >5 years; able to consent. Exclude: Evidence of distant metastatic disease outside pelvic nodes (including osseous involvement), conditions that preclude radiation, or factors preventing protocol compliance.Interventions & Evaluations: Baseline history/physical, vitals, performance status, labs (PSA, CBC w/diff, CMP/creatinine), pelvic MRI and PSMA-PET/CT; optional biopsy if feasible. External beam radiation therapy (LINAC/VMAT) with daily image guidance: pelvis 45 Gy in 25 fractions, followed by a sequential boost to PSMA/MRI-defined disease to 63-70.2 Gy in 10-14 additional fractions, with protocolized OAR constraints. All participants receive standard-of-care androgen deprivation therapy (ADT) for 6-24 months at the treating clinician's discretion. Weekly on-treatment visits; physician-assessed toxicities graded by CTCAE v5. Patient-reported outcomes (IPSS; FACT-P) at baseline and each in-person follow-up.Follow-up: Phone toxicity check 1 month post-RT; clinic at 4 months post-RT, then every 3 months thereafter until 24 months after completion of ADT. At each visit: H&P, CTCAE toxicity assessment, and PSA. If biochemical failure occurs, imaging (PSMA-PET/CT, CT and/or MRI) is obtained per standard of care to assess clinical progression.Endpoints/Design: Primary endpoint: acute (≤4 months post-RT) Grade ≥2 toxicity (all types). Secondary endpoints: 2-year biochemical progression-free survival; chronic toxicity and patient-reported outcomes from 4-24 months; 24-month local control, locoregional control, distant metastasis, and overall survival. Simon optimal two-stage design with interim analysis after the first 18 patients complete RT (stop if ≥8 have Grade ≥2 acute toxicity); total planned enrollment up to 54.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: PSMA-guided Salvage Radiation

• Study Type: Interventional
• Enrollment (Estimated): 54
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Taylor Johnson; Phone Number: 402-559-4596; Email: taylora.johnson@unmc.edu

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Recruiting
      • University of Nebraska Medical Center
      • Contact: IIT Office IIT Office; Phone Number: 402-559-4596; Email: IITOffice@unmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Prior biopsy proven prostate cancer for which they underwent a radical prostatectomy with curative intent.
2. Evidence of biochemical recurrence as defined by NCCN: Persistent positive PSA post-radical prostatectomy (RP) or an undetectable PSA after RP with a subsequent detectable PSA that increases on ≥2 determinations (PSA recurrence) or increases to PSA >0.1 ng/mL.
3. Targetable PSMA-avid lesion within the prostate bed, pelvic lymph nodes, or both and/or targetable lesion in prostate bed defined on MRI suspicious for local recurrence.
4. If lesions are amenable for biopsy this may be attempted, but biopsy proven recurrence/persistence is not required for trial enrollment.
5. Life expectancy greater than 5 years.
6. Karnofsky performance status ≥ 80 or Eastern Cooperative Oncology Group performance status ≤ 2 within 14 days prior to registration.
7. Age ≥ 30 years.
8. Patient must be able to provide study-specific informed consent prior to study entry.

Exclusion Criteria:

1. Evidence of distant metastatic disease outside the pelvic lymph nodes (including osseous pelvic disease).
2. Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse.
3. Relative or absolute contraindications to radiation therapy as determined by the treating physician. These include but are not limited to inflammatory bowel disease, connective tissue disorders (systemic lupus erythematosus, scleroderma, etc.), and genetic disorders that risk increased sensitivity to radiation therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: De-escalated PSMA-guided salvage radiation; Enrolled patients will receive an MRI and PSMA-PET/CT scan to identify locations of disease. The intervention will involve salvage radiation therapy to the prostate bed, pelvis, and pelvic nodes as indicated by imaging. External beam radiation therapy will consist of 45 Gy delivered in 25 daily fractions, followed by a sequential boost to PET-avid disease to 63-70.2 Gy in an additional 10-14 fractions.

Radiation: PSMA-guided Salvage Radiation; External beam radiation therapy will consist of 45 Gy delivered in 25 daily fractions, followed by a sequential boost to PET-avid disease to 63-70.2 Gy in an additional 10-14 fractions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Grade 2+ acute toxicity occurence	Determine the impact of de-escalated PSMA-guided salvage radiation on grade 2+ acute toxicity (i.e., <4 months) compared to historical controls.	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of biochemical progression-free survival	Determine if 2-year biochemical progression-free survival with de-escalated PSMA-guided salvage radiation is comparable to historical post-salvage radiation treatment.	2-years
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	Evaluate chronic toxicity from de-escalated PSMA-guided salvage radiation from 4 months to 2 years.	2-years
Overall Survival	Evaluate 24-month local control, locoregional control, distant metastasis, and overall survival.	2-years
Comparison of patient reported outcomes pre-, during follow-up, and post-study using the IPSS (International Prostate Symptom Score)	The IPSS (International Prostate Symptom Score) will be summarized using descriptive statistics at each time point collected as n, mean, SD, median, minimum, and maximum. Changes over time will be displayed graphically. Generalized linear mixed models will be used to look for changes over time while accounting for within subject correlation using a random effect. Scores for each question are tallied, a higher score is indicative of worse outcomes.	2-Years

Collaborators and Investigators

• Sponsor: University of Nebraska
• Investigators: Principal Investigator: Michael Baine, PhD/MD, University of Nebraska

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2026
• Primary Completion (Estimated): September 5, 2029
• Study Completion (Estimated): October 5, 2029

Study Registration Dates

• First Submitted: October 15, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Actual): November 19, 2025

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 733-25-FB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No