Two-session MR‑Linac radiotherapy with targeted dose reduction for intermediate‑risk prostate cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

DESTINATION 2 randomises 54 men with intermediate‑risk localized prostate cancer to receive two fractions of MR‑guided stereotactic body radiotherapy delivered on an MR‑Linac. One arm delivers a uniform 27 Gy in 2 fractions to the whole prostate and seminal vesicles with a 0 mm margin, while the other arm de‑escalates dose to benign prostate to 20 Gy in 2 fractions and boosts MRI‑visible intraprostatic tumor nodules to 27 Gy with a 4 mm GTV‑PTV margin. All treatments use daily MRI adaptation and allow concurrent androgen‑deprivation therapy where standard of care. Primary outcome is acute genitourinary CTCAE v5 grade 2+ toxicity within three months, with secondary endpoints including acute gastrointestinal toxicity, late toxicity, patient‑reported outcomes (EPIC‑26, IPSS, IIEF‑5) up to two years, and PSA control.

Why it matters

Who can join: the full rules

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 (Grade groups (GG) 1, 2 or 3)
4. MRI stage T3a or less (as staged by AJCC TNM 2018). MRI must be performed within a year of randomisation
5. 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
6. The MRI-defined lesion must be confirmed as malignant on biopsies (Gleason grade must be within the limits expressed in inclusion factor 3)
7. Patients can be concurrently treated with androgen deprivation therapy (ADT) if this would be standard of care. LHRH analogues, LHRH agonists or Bicalutamide are permitted. ADT is not mandatory where this would usually be omitted.
8. PSA \<20 ng/ml prior to starting ADT, if used
9. WHO Performance status 0-2
10. Ability of the participant understand and the willingness to sign a written informed consent form.
11. Willing to consent to contraception during and for 1 year after treatment when applicable.
12. 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. Severe GU symptoms that would preclude extreme hypofractionation per the discretion of the treating physician.
3. IPSS Score \> 19
4. High grade disease (GG3) occult to MRI-defined lesion. As a guide, any pathology for which you would consider surveillance (eg GG1, low volume GG2) is allowed outside of the MRI-defined area.
5. Prostate volume \>90cc
6. Comorbidities which predispose to significant toxicity (e.g. inflammatory bowel disease) or preclude long term follow up
7. Hip replacement, or other pelvic metalwork which causes significant artefact on diffusion-weighted imaging
8. Previous pelvic radiotherapy
9. Patients needing \>6 months of ADT due to disease parameters.
10. Previous invasive malignancy within the last 2 years where this is likely to shorten lifespan the following will remain eligible: basal or squamous carcinomas of the skin, low risk non-muscle invasive bladder cancer (assuming cystoscopic follow up now negative) or small renal masses on surveillance.
11. Participating in another interventional trial for prostate cancer

Where it's running

• The Christie NHS Foundation Trust
  Manchester, United Kingdom Recruiting
• The Royal Marsden NHS Foundation Trust
  Sutton, United Kingdom Recruiting
• Sunnybrook Health Sciences Centre
  Toronto, Canada Not yet recruiting

Study contacts

• Study coordinator: Francesca Mason
• Email: mrltrials@rmh.nhs.uk
• Phone: +44 20 3186 5157

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.