Primary Endpoint Analysis of the Phase 2 DESTINATION-MRL Trial for Patients With Intermediate-Risk Prostate Cancer

Area of Science:

• Radiation Oncology
• Medical Physics
• Prostate Cancer Treatment

Background:

• Minimizing toxicity in intermediate-risk prostate cancer requires dose de-escalation to the prostate clinical target volume (CTV) while escalating dose to the gross tumor volume (GTV).
• Online adaptive magnetic resonance imaging (MRI)-guided stereotactic body radiation therapy (SBRT) offers potential for precise dose delivery.
• A 0-mm planning target volume (PTV) margin is explored to reduce toxicity without compromising outcomes.

Purpose of the Study:

• To evaluate the technical feasibility of dose-escalated GTV and dose-de-escalated CTV with a 0-mm PTV margin in MRI-guided SBRT for prostate cancer.
• To assess the ability to achieve robust target coverage in online adaptive MRI-guided SBRT for intermediate-risk prostate cancer.

Main Methods:

• The DESTINATION-MRL trial involved 3 parallel single-center phase 2 non-randomized trials with 20 patients each, treated on a 1.5T MR-Linac.
• Patients received 30 Gy to the CTV (whole prostate) and an isotoxic boost of 45 Gy to the GTV with a 4-mm margin (GTV 4 mm).
• Technical feasibility was defined as achieving a GTV D90% >42 Gy on post-treatment MRI in at least 90% of patients.

Main Results:

• Out of 60 treated patients, 54 were analyzed. An accumulated GTV D90% >42 Gy was achieved in 85% of patients (46/54).
• Feasibility criteria were met in 71% of patients at institute 1 and 90% at institutes 2 and 3.
• Institute-level analysis revealed variability in achieving the primary endpoint.

Conclusions:

• Online adaptive MRI-guided SBRT for prostate cancer, aiming to minimize toxicity, was feasible in 2 of 3 participating institutes.
• Robust coverage of both GTV and CTV could not be consistently assured across all patients and institutes without employing a gating strategy.
• Further optimization, potentially including gating, is necessary to ensure reliable target coverage in this treatment approach.