Hypofractionated Image-Guided Radiotherapy (IGRT) With Organ Motion Mitigation and Urethral Sparing for Prostate Cancer

Fundacao Champalimaud

Status: Completed

Conditions: Adenocarcinoma of the Prostate

Treatments: Device: Urethral catheter loaded with beacon transponders; Radiation: Ultra-hypofractionated IGRT-VMAT with organ-motion mitigation and urethral sparing; Device: Rectal balloon with air filling

Study type: Interventional

Funder types: Other

Identifiers

NCT02761889

HYPO

Details and patient eligibility

About

The present study evaluates the safety, feasibility, quality-of-life effects, PSA kinetics, and clinical outcomes of definitive dose-escalated external beam radiotherapy for localized adenocarcinoma of the prostate.

Eligible patients will have biopsy-proven localized prostate adenocarcinoma without radiographic evidence of regional or distant metastases and without MRI evidence of radiographic T3/T4 disease. Patients may have low-risk, intermediate-risk, or selected high-risk disease. Previous or concomitant hormonal therapy is allowed but is not required, provided prior hormonal therapy was not given for more than 6 months before protocol therapy.

Patients enrolled in the study will receive image-guided volumetric modulated arc radiotherapy (IGRT-VMAT) to 45 Gy in five fractions of 9 Gy each, delivered on five consecutive treatment days unless a clinically or operationally justified interruption is required. Treatment will use organ-motion mitigation, urethral localization, online target tracking, urethral sparing, and treatment-planning quality assurance procedures designed to support normal tissue sparing and accurate radiation delivery. A rectal balloon with air filling will be used for prostate immobilization and anatomical reproducibility, and a urethral catheter loaded with beacon transponders will be used for set-up reproducibility and online tracking.

Patients will be followed at approximately 1 month after treatment, then at approximately 3, 6, 9, and 12 months, and every 6 months thereafter through 60 months. Patients will be followed for a minimum of 5 years. Follow-up assessments will include physician-graded gastrointestinal and genitourinary toxicity using NCI CTCAE v4.0, patient-reported urinary, bowel, and sexual quality-of-life outcomes using validated instruments including EPIC, IPSS, and IIEF questionnaires, and serum PSA testing. Biochemical relapse-free survival will be assessed using the Phoenix definition, and recurrence patterns will be summarized from clinically indicated imaging.

Full description

This is a prospective, single-arm phase II study of definitive ultra-hypofractionated image-guided radiotherapy for localized prostate adenocarcinoma. The study is designed to evaluate the acute and late safety profile, feasibility, patient-reported quality-of-life outcomes, PSA kinetics, biochemical relapse-free survival, and clinical outcomes of dose-escalated IGRT-VMAT using organ-motion mitigation and urethral sparing.

Patients will receive 45 Gy in 5 fractions of 9 Gy each. Treatment planning will use CT/MRI-based target and organ-at-risk delineation. The protocol incorporates a rectal balloon for prostate stabilization and anatomical reproducibility, a urethral catheter loaded with beacon transponders for urethral localization and online motion tracking, and inverse dose-painting to reduce urethral dose when compatible with target coverage and disease anatomy. Erectile-related structures, including the neurovascular bundles, urogenital diaphragm, and penile bulb, may be contoured and recorded for quality-of-life and dosimetric analyses.

The primary safety assessments are treatment-related Grade 3 or higher gastrointestinal or genitourinary toxicity occurring from the first protocol fraction through 90 days after treatment completion, and treatment-related late Grade 2 or higher gastrointestinal or genitourinary toxicity occurring more than 90 days through 5 years after completion of radiotherapy. Late Grade 3 or higher gastrointestinal or genitourinary toxicity will be summarized separately. Clinically meaningful deterioration from baseline in urinary, bowel, and sexual patient-reported outcomes will be evaluated as a key safety and quality-of-life assessment.

Secondary assessments include PSA kinetics, biochemical relapse-free survival using the Phoenix definition, quality-of-life changes measured by EPIC, IPSS, and IIEF instruments, erectile and sexual function preservation, associations between clinical or dosimetric factors and outcomes, hormonal therapy exposure, and patterns of recurrence on clinically indicated imaging.

Enrollment: 444 patients

Sex: Male

Ages: 40+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Participants must meet all of the following criteria:

• Signed study-specific informed consent.
• Histologic confirmation of adenocarcinoma of the prostate by biopsy.
• Localized low-risk, intermediate-risk, or selected high-risk adenocarcinoma of the prostate. Selected high-risk disease is limited to patients with no MRI evidence of radiographic T3/T4 disease and no radiographic regional or distant metastases.
• No direct evidence of regional or distant metastases after appropriate staging studies.
• Previous or concomitant hormonal therapy is allowed but not required. - Previous hormonal therapy must not have been given for more than 6 months before protocol therapy.
• Age ≥40 years.
• Performance status 0-2.
• IPSS score ≤20; alpha blockers are allowed.
• CT- or ultrasound-based prostate volume estimate ≤150 grams.

Participants meeting any of the following criteria are ineligible:

• Metastatic prostate cancer on imaging studies.
• MRI evidence of radiographic T3 or T4 disease.
• Previous pelvic radiotherapy.
• Previous surgery for prostate cancer.
• Previous hormonal therapy given for more than 6 months before protocol therapy.
• History of Crohn's disease or ulcerative colitis.
• Significant obstructive urinary symptoms, defined as IPSS >20.
• Significant psychiatric illness that would interfere with protocol participation.
• Severe active comorbidity that, in the investigator's judgment, would preclude safe protocol therapy or required follow-up.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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444 participants in 1 patient group

Experimental: Ultra-hypofractionated IGRT-VMAT 45 Gy in 5 fractions of 9 Gy

Experimental group

Description:

Participants will receive definitive dose-escalated image-guided volumetric modulated arc radiotherapy for localized prostate adenocarcinoma. Radiotherapy will be delivered to 45 Gy in 5 fractions of 9 Gy each over 5 consecutive days, using organ-motion mitigation, urethral localization, online target tracking, urethral sparing, rectal balloon stabilization, and protocol-specified treatment planning and quality assurance procedures.

Treatment:

Device: Rectal balloon with air filling

Radiation: Ultra-hypofractionated IGRT-VMAT with organ-motion mitigation and urethral sparing

Device: Urethral catheter loaded with beacon transponders