Single-Dose Image-Guided Radiotherapy With Urethral Sparing and DIL Boost for Intermediate-Risk Prostate Cancer (PROSINT II) (PROSINT II)

May 7, 2026 updated by: Carlo Greco, MD, Fundacao Champalimaud

Phase II Study of Single-Dose Image-Guided Radiotherapy (SDRT) With Urethral Sparing and Dose-Escalated Dominant Intraprostatic Lesion Simultaneous Integrated Boost for Intermediate-Risk Prostate Cancer (PROSINT II)

This prospective single-arm phase II study evaluates the safety, feasibility, quality-of-life effects, PSA kinetics, imaging response, and clinical outcomes of definitive ultra-high dose single-fraction external beam radiation therapy in patients with biopsy-proven NCCN intermediate-risk localized adenocarcinoma of the prostate.

All eligible patients receive image-guided volumetric modulated arc radiotherapy with urethral sparing and organ-motion mitigation. Treatment consists of 24 Gy in one fraction to the whole prostate gland and proximal seminal vesicles. Patients with NCCN unfavorable intermediate-risk disease and an imaging-defined dominant intraprostatic lesion may receive a PSMA PET/CT-guided simultaneous integrated boost to the dominant intraprostatic lesion in sequential dose-escalation cohorts, up to 30 Gy, while maintaining protocol-defined organ-at-risk constraints.

A rectal balloon with air filling is used for prostate target immobilization and anatomical reproducibility, and a urethral catheter loaded with beacon transponders is used to identify the urethra, support urethral sparing, and enable online target tracking. Toxicity is assessed using CTCAE v4.0, and patient-reported outcomes are assessed using EPIC-26, IPSS, and IIEF questionnaires. PSA is measured at protocol-defined follow-up visits. Multiparametric MRI is performed at baseline and at 12 and 24 months after treatment. Participants are followed for a minimum of 5 years.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This prospective phase II study evaluates the safety, feasibility, quality-of-life effects, prostate-specific antigen kinetics, imaging response, and clinical outcomes of definitive ultra-high-dose single-fraction external beam radiotherapy in patients with biopsy-proven NCCN intermediate-risk localized adenocarcinoma of the prostate.

The study investigates single-dose image-guided radiotherapy using image-guided volumetric modulated arc therapy with urethral sparing, organ-motion mitigation, and online target tracking. All eligible participants receive single-fraction radiotherapy to the prostate gland and proximal seminal vesicles. The whole-gland prescription dose is 24 Gy delivered in one treatment session. Participants with NCCN unfavorable intermediate-risk disease and an imaging-defined dominant intraprostatic lesion may also receive a prostate-specific membrane antigen PET/CT-guided simultaneous integrated boost to the dominant intraprostatic lesion. The boost is delivered in sequential dose-escalation cohorts up to a target dose of 30 Gy, while maintaining protocol-defined organ-at-risk dose constraints.

The rationale for the study is based on the radiobiological sensitivity of prostate cancer to large radiation fraction sizes, the clinical experience with extreme hypofractionation in localized prostate cancer, and prior institutional experience with prostate image-guided radiotherapy using target immobilization, urethral localization, and online tracking. Prior studies at the study institution have suggested that ultra-hypofractionated and single-fraction prostate radiotherapy can be delivered with acceptable toxicity when careful target stabilization, urethral sparing, and treatment-planning quality assurance procedures are used. In unfavorable intermediate-risk disease, intraprostatic recurrence may occur preferentially at the site of the dominant lesion, supporting the investigation of dose escalation to the dominant intraprostatic lesion while preserving strict normal tissue constraints.

Participants undergo pretreatment evaluation including history and physical examination, pathology confirmation, serum PSA assessment, laboratory testing, and multiparametric MRI of the prostate. PSMA PET/CT is required for participants being considered for PSMA-guided dominant intraprostatic lesion boost and may also be used when clinically indicated for staging. Imaging datasets are used for treatment planning and, when applicable, dominant intraprostatic lesion definition.

Radiotherapy is delivered using image-guided volumetric modulated arc therapy. A rectal balloon filled with air is used to improve prostate immobilization and anatomical reproducibility. A Foley catheter loaded with beacon transponders is used to identify the urethra, support urethral-sparing treatment planning, and enable setup reproducibility and online target tracking. Treatment planning includes delineation of the prostate, proximal seminal vesicles, urethra, rectal wall, bladder wall, bowel, urogenital diaphragm, penile bulb, neurovascular bundles, femoral heads, and other protocol-specified organs at risk. Urethral sparing is incorporated using an avoidance structure around the catheter-defined urethra. Erectile-related structures are contoured and recorded for quality-of-life and dosimetric analyses when compatible with target coverage and disease anatomy.

For participants receiving a dominant intraprostatic lesion boost, the lesion is defined using PSMA PET uptake co-localized with multiparametric MRI abnormality. Sequential boost cohorts may include 24 Gy whole-gland treatment without boost, followed by dominant intraprostatic lesion boost dose levels of 26.4 Gy, 28.8 Gy, and 30 Gy. Organ-at-risk constraints remain unchanged across dose levels. Escalation to the next boost dose level occurs only after review of acute toxicity, patient-reported outcomes, protocol deviations, and treatment-plan constraint adherence in the preceding cohort. Dose-limiting toxicity for escalation monitoring is defined as CTCAE v4.0 grade 3 or higher acute genitourinary or gastrointestinal toxicity occurring within 90 days after treatment.

The primary clinical endpoint is the incidence of acute physician-assessed CTCAE v4.0 grade 2 or higher genitourinary and/or gastrointestinal toxicity occurring within 90 days after treatment. Key patient-reported safety endpoints include clinically meaningful changes from baseline in urinary and bowel function within 90 days, assessed using the International Prostate Symptom Score and EPIC-26 questionnaires. Secondary endpoints include late genitourinary and gastrointestinal toxicity, longitudinal patient-reported urinary, bowel, and sexual quality-of-life outcomes, sexual-function outcomes assessed using IIEF and the EPIC-26 sexual domain, PSA kinetics, biochemical relapse-free survival using the Phoenix definition, MRI-based imaging response, and patterns of local, regional, nodal, and distant failure assessed by clinically indicated imaging, including PSMA PET/CT.

Participants are followed after treatment at approximately 1 month, every 3 months through 12 months, every 6 months through 60 months, and annually thereafter. Follow-up evaluations include toxicity assessment, patient-reported quality-of-life questionnaires, serum PSA measurements, and clinical assessment of urinary, rectal, and sexual function. Multiparametric MRI is performed at baseline and at 12 and 24 months after treatment. Participants are monitored for a minimum of 5 years. Biochemical relapses are evaluated with imaging, including MRI and PSMA PET/CT when clinically indicated, to characterize recurrence as local, nodal/regional, distant, or combined.

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Portugal
      • Lisbon, Portugal, 1400-038
        • Recruiting
        • Champalimaud Foundation
        • Contact:
          • Manuela Seixas
          • Phone Number: +351 9675289072

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion criteria

Participants must meet all of the following criteria:

Signed study-specific informed consent form Histologic confirmation of adenocarcinoma of the prostate by biopsy Biopsy ISUP grade 1-3 Biopsy-proven localized intermediate-risk prostate cancer according to NCCN criteria No previous hormonal therapy PSA ≤20 ng/mL Staging multiparametric MRI confirmation of AJCC cT1c-cT2c disease, with no radiographic evidence of cT3, cT4, or N1 disease No direct evidence of regional or distant metastases after appropriate staging studies Age ≥18 years Performance status 0-2 IPSS score ≤15; alpha-blockers allowed CT- or ultrasound-based prostate gland volume estimate ≤100 grams

Exclusion criteria

Participants with any of the following are ineligible:

Positive lymph nodes or metastatic disease from prostate cancer on imaging studies MRI evidence of radiographic T3, T4, or N1 disease Biopsy ISUP grade ≥4 Previous pelvic radiotherapy Previous surgery for prostate cancer Previous transurethral resection of the prostate within 3 months Contraindication to protocol-required Foley catheter placement, rectal-balloon placement, MRI, PSMA PET/CT where required, or treatment immobilization/tracking procedures Active urinary tract infection, unresolved acute prostatitis, or other acute condition judged by the investigator to make simulation or SDRT unsafe until resolved Previous hormonal therapy History of Crohn's disease or ulcerative colitis Previous significant obstructive symptoms Significant psychiatric illness CT- or ultrasound-estimated prostate volume >100 grams Severe active comorbidity judged by the investigator to preclude protocol treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single-dose IGRT-VMAT with urethral sparing ± PSMA-guided DIL-SIB
Participants receive single-fraction image-guided volumetric modulated arc radiotherapy to the whole prostate gland and proximal seminal vesicles, with urethral sparing, rectal-balloon immobilization, and online tracking using a urethral catheter loaded with beacon transponders. The whole-gland prescription dose is 24 Gy in 1 fraction. Participants with NCCN unfavorable intermediate-risk disease and an imaging-defined dominant intraprostatic lesion may receive PSMA PET/CT-guided simultaneous integrated boost to the dominant intraprostatic lesion in sequential cohorts to 26.4 Gy, 28.8 Gy, or 30 Gy, while satisfying the same organ-at-risk constraints.
Device: Rectal balloon with air filling
A rectal balloon with air filling will be used for prostate target immobilization and anatomical reproducibility.
Device: Urethral catheter loaded with beacon transponders
A urethral catheter loaded with beacon transponders will be used to ensure set-up reproducibility and online target tracking.
Radiation: IGRT-VMAT / SDRT 24 Gy in 1 fraction
PSMA PET/CT-guided dominant intraprostatic lesion simultaneous integrated boost
Diagnostic test: PSMA PET/CT for DIL definition and/or staging where protocol-required
PSMA PET/CT for DIL definition
Diagnostic test: Planning MRI for organ at risk and target definition
Planning MRI for organ at risk and target definition. mpMRI will also be used to aid DIL definition in conjunction with PSMA-PET/CT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of acute grade ≥2 GU and/or GI toxicity
Time Frame: Treatment through 90 days after treatment
Proportion of treated participants with physician-assessed CTCAE v4.0 grade ≥2 genitourinary and/or gastrointestinal toxicity occurring from protocol treatment through 90 days after treatment.
Treatment through 90 days after treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Late GU and GI toxicity
Time Frame: >90 days
Incidence and grade of physician-assessed CTCAE v4.0 GU and GI toxicity occurring more than 90 days after treatment.
>90 days
Dose-limiting acute GU/GI toxicity
Time Frame: Treatment through 90 days
Proportion of participants with CTCAE v4.0 grade ≥3 acute GU or GI toxicity within 90 days after treatment, used for DIL-SIB cohort-escalation safety monitoring.
Treatment through 90 days
Quality-of-life change over time
Time Frame: Baseline through 5 years
Change from baseline in EPIC-26 scores. The EPIC-26 (Expanded Prostate Cancer Index Composite score) questionnaire ranges between 0 and 100, with higher values indicating better quality of life.
Baseline through 5 years
Clinically meaningful EPIC-26 urinary decline
Time Frame: Baseline through 90 days; longitudinally through 5 years
Proportion of participants with EPIC-26 urinary-domain decline ≥6 points from baseline. The EPIC-26 (Expanded Prostate Cancer Index Composite score) questionnaire ranges between 0 and 100, with higher values indicating better quality of life.
Baseline through 90 days; longitudinally through 5 years
Clinically meaningful urinary symptom worsening
Time Frame: Baseline through 90 days; longitudinally through 5 years
Proportion of participants with IPSS increase ≥4 points from baseline. CThe IPSS (International Prostatic Symptoms Score) questionnaire ranges between 0 and 35 with higher values indicating worse urinary symptoms.
Baseline through 90 days; longitudinally through 5 years
Clinically meaningful EPIC-26 bowel decline
Time Frame: Baseline through 90 days; longitudinally through 5 years
Proportion of participants with EPIC-26 bowel-domain decline ≥5 points from baseline. . The EPIC-26 (Expanded Prostate Cancer Index Composite score) questionnaire ranges between 0 and 100, with higher values indicating better quality of life.
Baseline through 90 days; longitudinally through 5 years
Sexual-function outcomes
Time Frame: Baseline through 5 years
Change from baseline in IIEF (International Index of Erectile Function ) sexual-domain scores (from 0 to 30 with higher scores indicating better erectile function), including exploratory assessment of neurovascular-bundle sparing where applicable.
Baseline through 5 years
PSA kinetics
Time Frame: Baseline through 5 years
PSA values over time, including PSA nadir and time to nadir.
Baseline through 5 years
Biochemical relapse-free survival
Time Frame: Through 5 years
Biochemical relapse-free survival using the Phoenix definition, PSA nadir + 2 ng/mL.
Through 5 years
MRI-based imaging response
Time Frame: 12 and 24 months after treatment
Imaging response assessed using multiparametric MRI.
12 and 24 months after treatment
Patterns of recurrence
Time Frame: Through 5 years
Local, regional/nodal, distant, or combined recurrence pattern assessed by clinically indicated imaging, including MRI and PSMA PET/CT.
Through 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fundacao Champalimaud

Investigators

  • Principal Investigator: Carlo Greco, MD, Fundação Champalimaud

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2019

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2030

Study Registration Dates

First Submitted

July 23, 2019

First Submitted That Met QC Criteria

July 25, 2019

First Posted (Actual)

July 29, 2019

Study Record Updates

Last Update Posted (Actual)

May 8, 2026

Last Update Submitted That Met QC Criteria

May 7, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PROSINT II

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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