Dose De-escalation in Prostate Radiotherapy Using an MR-Linac in Two Fractions (DESTINATION 2)

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

The goal of this clinical trial is to find out whether lowering the radiation dose to parts of the prostate without visible tumor on MRI can reduce side effects while still effectively treating prostate cancer in men with low or intermediate-risk prostate cancer.

The main questions it aims to answer are:

• Does reducing the radiation dose to healthy prostate tissue lower the risk of bowel and urinary side effects?
• Can we maintain good cancer control by keeping a high dose for MRI-visible tumor areas?

Researchers will compare two treatment approaches:

• One group receives a uniform high dose to the entire prostate.
• The other group receives a lower dose to healthy prostate tissue and a high dose only to visible tumor areas.

Participants will:

• Receive two sessions of MRI-guided radiotherapy using an MR-Linac.
• Complete questionnaires about urinary, bowel, and sexual health before and after treatment.
• Have follow-up visits to monitor side effects and PSA levels for up to 2 years.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer (Adenocarcinoma)
• Intervention / Treatment: Radiation: uniform dose radiotherapy; Radiation: De-escalated dose radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 54
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Floris Pos, MD, PhD; Phone Number: +31205129111; Email: f.pos@nki.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1066CX
    • Recruiting
    • The Netherlands Cancer Institute
    • Contact: Floris Pos, MD, PhD; Phone Number: +31205129111; Email: f.pos@nki.nl
    • Contact: Email: l.vd.hengel@nki.nl

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Uniform dose SBRT	Radiation: uniform dose radiotherapy; 27 Gy dose in 2 fractions to the whole prostate+/- seminal vesicles with a 0mm PTV margin using MR-linac
Other: De-escalated dose SBRT	Radiation: De-escalated dose radiotherapy; The benign prostate +/- SV CTV will receive 20 Gy in 2 fractions with a 0mm PTV margin using MR-linac. The intraprostatic tumor masses (on MRI) will receive 27 Gy in 2 fractions. A 4mm GTV to PTV margin will be added to the in-traprostatic MR visible tumour to form PTV 27Gy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute GU toxicity	Physician-reported acute Grade 2 or higher CTCAE GU toxicity observed within 13 weeks of starting radiotherapy	within 13 weeks of starting radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dosimetry	Estimate the accumulated dose differences between treatment arms in terms of dose to prostate CTV, rectum, urethra and bladder	During Radiotherapy treatment of 8 days
Late GI toxicity	Physician reported late GI toxicity according to CTCAE v5.0	1 and 2 years after radiotherapy treatment
Biochemical relapse-free survival	Assess biochemical relapse-free survival for 2 years	2 years
Severity of erectile dysfunction experienced by patient	The IIEF-5 patient reported outcomes (PROs) assess the acute severity of erectile dysfunction	Before radiotherapy treatment, and at 6, 12 and 24 months after radiotherapy treatment
Acute GI toxicity	Physician reported acute GI toxicity according to CTCAE v5.0	At baseline, after the last fraction, and 2, 4 and 12 weeks after radiotherapy treatment
Late GU toxicity	Physician reported late GU toxicity according to CTCAE v5.0	1 and 2 years after radiotherapy treatment
Late sexual toxicity	Physician reported late sexual toxicity according to CTCAE v5.0	1 and 2 years after radiotherapy treatment
Severity of urinary symptoms (GU) experienced by patient	The patient reported outcomes (PROs) International Prostate Symptoms Score (IPSS) assess the severity of urinary symptoms what the patient experiences	Before radiotherapy treatment, after the last fraction, at 2, 4 and 12 weeks post-treatment, and at 6, 12 and 24 months after radiotherapy treatment
Health-related quality of life experienced by patient	The EPIC-26 patient reported outcomes (PROs) assess the health-related quality of life	Before start radiotherapy, week 4 and week 12, at 6, 12 and 24 months after radiotherapy treatment.

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute
• Collaborators: Elekta Limited; MRL Consortium

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: October 2, 2025
• First Submitted That Met QC Criteria: February 2, 2026
• First Posted (Actual): February 6, 2026

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Radiotherapy; De-escalation; MR-Linac
• 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; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Prostatic Neoplasms; Adenocarcinoma
• Other Study ID Numbers: M24DTI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: It is intended that data will be shared within the MOMENTUM collaboration, between centres delivering treatment in the same way as DESTINATION2. Pseudonymised data will be stored within MOMENTUM for at least 5 years. Storage will be cloud based and as the treating centre we will have free access to the data and control over who else can assess it.
• IPD Sharing Time Frame: 5 years

Drug and device information, study documents

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