What question did this study set out to answer?

The trial aims to assess if lower doses to prostate tissue reduce side effects while preserving control over cancer in localized prostate cancer.

May 9, 2026Open Access

Dose dE-eScalaTion IN prostATe radIOtherapy usiNg an MR-Linac in 2 Fractions (DESTINATION 2): protocol for a randomised, phase II/R-IDEAL2b trial

Key Points

The trial aims to assess if lower doses to prostate tissue reduce side effects while preserving control over cancer in localized prostate cancer.
200 men with localized, MRI-visible prostate cancer randomized 1:1 to receive either SBRT or de-escalated SBRT.
Interventions include either standard 27 Gy SBRT to the prostate or reduced 20 Gy to the prostate with higher doses to visible tumors.
Primary endpoint focuses on acute grade 2+ genitourinary adverse events within 12 weeks post-treatment.
The primary endpoint is measuring the reduction of acute grade 2+ GU adverse events.
Secondary endpoints include various adverse events, dosimetry assessments, and 2-year biochemical relapse-free survival.
Results will be shared through peer-reviewed publications and conferences.

Abstract

Introduction Stereotactic body radiotherapy (SBRT) delivered on an MRI-guided linear accelerator (MR-linac) enables highly conformal prostate cancer irradiation. The DESTINATION 2 trial is a federated, randomised phase II/R-IDEAL 2b study evaluating whether de-escalating the dose to prostate tissue, while maintaining a high dose to MRI-visible tumour(s) in two fractions, reduces genitourinary (GU) treatment-related adverse events (AE) without compromising disease control in men with localised prostate cancer. Methods 200 men worldwide with localised, MRI-visible prostate cancer will be randomised 1:1 to receive either (1) prescribed uniform dose MR-linac SBRT (27 Gy in two fractions to the whole prostate and seminal vesicles with 0 mm CTV-PTV margin) or (2) de-escalated SBRT (20 Gy in two fractions to whole prostate with 0 mm CTV-PTV margin and 27 Gy in two fractions to MRI-visible tumour(s) with a 4 mm intraprostatic margin applied to the GTV. All treatments are delivered using MRI-guided adaptive Radiotherapy (MRIgRT). The primary endpoint is the absolute and relative risk reduction in acute grade 2+GU AE (CTCAE v5) within 12 weeks of completing radiotherapy. Secondary endpoints include late GU AE, acute and late gastrointestinal (GI) AE, sexual AE, patient-reported outcomes, dosimetry, technical feasibility and 2-year biochemical relapse-free survival. Ethics and dissemination This is a federated trial design in which each centre operates independently with its own sponsor, ethics committee approval and regulatory oversight. Each centre is responsible for obtaining and maintaining local ethics approval in accordance with their national and institutional requirements. The UK centre (The Royal Marsden NHS Foundation Trust) has received ethical approval from the East of England–Cambridge South Research Ethics Committee (REC reference: 24/EE/0163; IRAS: 338368). Results will be disseminated via peer-reviewed publications and conference presentations. Trial registration number NCT06638541 .

Dose dE-eScalaTion IN prostATe radIOtherapy usiNg an MR-Linac in 2 Fractions (DESTINATION 2): protocol for a randomised, phase II/R-IDEAL2b trial

Key Points

Abstract

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