Two-fraction MR-guided prostate radiation with lower dose to healthy prostate and a boost to MRI-visible tumor

Dose De-escalation in Prostate Radiotherapy Using an MR-Linac in 2 Fractions

This will test whether giving two MRI-guided radiation sessions that lower dose to normal prostate tissue but keep a high dose to MRI-visible tumors reduces urinary and bowel side effects in men with low- or favorable-intermediate risk prostate cancer.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: The Netherlands Cancer Institute (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Amsterdam)
• Trial ID: NCT07391982 on ClinicalTrials.gov

What this trial studies

Men with low or favorable-intermediate risk prostate cancer and an MRI-visible lesion are randomly assigned to receive either a uniform high dose to the whole prostate or a de-escalated dose to MRI-normal prostate with a high-dose boost to the MRI-visible tumor, delivered in two MR-Linac sessions. Treatments are delivered using MRI guidance to precisely target the lesion and spare surrounding tissue. Participants complete urinary, bowel, and sexual health questionnaires and have regular follow-up visits with PSA monitoring for up to two years to track side effects and cancer control. The trial compares toxicity profiles and early cancer-control outcomes between the two approaches.

Who should consider this trial

Good fit: Men aged 18 or older with biopsy-confirmed prostate adenocarcinoma (Gleason 3+3, 3+4, or 4+3), an MRI-visible lesion (PIRADS ≥3) ≤2.5 cm confirmed malignant on biopsy, clinical stage up to mT2 or select mT3a with minimal extracapsular extension, PSA <20 ng/ml before ADT, and WHO performance status 0–2 are ideal candidates.

Not a fit: Patients with high-risk or widely multifocal disease, lesions larger than 2.5 cm or not visible on MRI, metastatic disease, prior pelvic radiotherapy, or PSA ≥20 ng/ml are unlikely to benefit from this focal de-escalation approach.

Why it matters

Potential benefit: If successful, this approach could reduce urinary and bowel side effects while keeping cancer control, using only two MRI-guided treatment sessions.

How similar studies have performed: Prior focal-boost and SBRT studies have shown promising cancer control and reduced toxicity, but using a two-fraction MR-Linac de-escalation strategy is relatively novel and not yet widely tested.

Eligibility criteria

Inclusion Criteria:

1. Men aged ≥18 years
2. Histological confirmation of prostate adenocarcinoma requiring radical radiotherapy
3. Gleason score 3+3, 3+4 or 4+3 (ISUP Grade groups (GG) 1, 2 or 3)
4. MRI-visible tumour(s) of PIRADS v2 grade 3 or higher and able to be delineated on T2 and diffusion-weighted imaging +/- dynamic contrast-enhanced imaging. Tumour nodule visible on MRI should be considered able to be boosted by treating clinician and \<2.5cm in maximal dimension. MRI must be performed within 3 months of trial entry
5. The MRI-defined lesion must be confirmed as malignant on biopsies (any Gleason grade is sufficient as long as Gleason score is reported).
6. MRI stages mT1 and T2 or mT3a with ≤ 1mm tumour outside gland AND otherwise favourable intermediate risk characteristics (Gleason 3+3, 3+4)(as staged by AJCC TNM 2018)
7. PSA \<20 ng/ml prior to starting androgen deprivation therapy (ADT).
8. WHO Performance status 0-2
9. Ability of the participant to understand and the willingness to sign a written informed consent (IC) form.
10. Ability/willingness to comply with the patient reported outcome questionnaires schedule throughout the study.

Exclusion Criteria:

1. Contraindications to MRI (e.g. pacemaker, potentially mobile metal implant, claustrophobia)
2. IPSS Score \> 19
3. High grade disease (GG3) occult to MRI-defined lesion. As a guide, any pathology for which you would consider surveillance is allowed outside of the MRI-defined area.
4. Prostate volume \>90cc
5. Comorbidities which predispose to significant toxicity (e.g. inflammatory bowel disease) or preclude long term follow up
6. Hip replacement, or other pelvic metalwork which causes artefact on diffusion-weighted imaging
7. Previous pelvic radiotherapy
8. Patients needing \>6 months of ADT due to disease parameters.
9. Previous invasive malignancy within the last 2 years excluding basal or squamous cell carcinomas of the skin, low risk non-muscle invasive bladder cancer (assuming cystoscopic follow up now negative) or small renal masses on surveillance.

Where this trial is running

Amsterdam

• The Netherlands Cancer Institute — Amsterdam, Netherlands (Recruiting)

Study contacts

• Study coordinator: Floris Pos, MD, PhD

Conditions Prostate Cancer; De-escalation; Radiotherapy; MR-Linac