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

Escalating dose to the gross tumor volume (GTV) while de-escalating dose to the prostate clinical target volume (CTV) and using a 0-mm planning target volume margin can potentially minimize toxicity without compromising biochemical control in patients with intermediate-risk prostate cancer. We evaluated the technical feasibility of this approach in online adaptive magnetic resonance imaging (MRI)-guided stereotactic body radiation therapy.

The DESTINATION-MRL trial ran as 3 parallel single-center phase 2 non-randomized trials in 3 different institutes. Each institute enrolled 20 patients who were all treated on a 1.5T Unity MR-linear accelerator (MR-Linac). The GTV was defined as tumor(s) visible on multiparametric MRI. The CTV was defined as the whole prostate. The proximal 1-2 cm of the seminal vesicles were included in the CTV at the clinician's discretion. An intraprostatic margin of 4 mm was applied to the GTV to account for delineation and pathological uncertainty (GTV 4 mm) and no planning target volume margin was applied to the CTV. All patients were treated with 30 Gy in 5 fractions to the CTV and an isotoxic boost of 45 Gy to the GTV 4 mm. The primary endpoint was technical feasibility, defined as an accumulated GTV D90% of >42 Gy on the post-treatment MRI in ≥90% of the patients.

Between May 2023 and September 2024, 60 patients were treated, of which 54 were included for analysis. An accumulated GTV D90% of >42 Gy was reached in 46 patients (85%). Analysis per institute showed that this criterion was reached in 10 of 14 patients (71%) in institute 1 and in 18 of 20 patients (90%) in both institutes 2 and 3.

Although toxicity-minimizing radiation therapy in online adaptive MRI-guided stereotactic body radiation therapy for prostate cancer was feasible in 2 of the 3 institutes, robust coverage of the GTV and CTV could not be assured in the absence of a gating strategy.