VMAT Focal Boost to MRI-Defined Intraprostatic Lesion in Localized Prostate Cancer: Results of a Phase II Trial

Abstract

Advances in the identification of the dominant intraprostatic lesion (DIL) with multi-parametric magnetic resonance imaging (mpMRI) have enabled selective focal radiation dose intensification. The aim of this prospective phase II trial was to determine the PSA and mpMRI response, toxicity and quality of life (QOL) in men with localized prostate cancer (PCa) treated with image-guided focal boost to the DIL. We report early results on local and biological control and toxicity. The hypothesis is that differential boosting with focal dose escalation to an mpMRI defined DIL is associated with a higher clinical control without a significant increase in toxicity.From February 2017 to January 2020, 30 patients with intermediate and high risk PCa with a visible DIL identified on mpMRI were included in a prospective phase II trial. Matching point registration of planning TC and T2-weighted, diffusion-weighted and a gradient recalled echo (GRE) MRI images made in treatment position was used for prostate and DIL delineation. Treatment consisted on 35 daily fractions of 2.17 Gy with a concomitant focal boost to the intraprostatic nodule of 2.43 Gy using VMAT (volumetric modulated arc therapy) and IGRT (image guided radiation therapy) with daily CBCT (cone beam CT) and intraprostatic fiducial markers. Androgen derivation therapy (ADT) was allowed for unfavorable intermediate and high-risk tumors. Biochemical failure was analyzed using nadir+2 ng/ml criteria and local control using mpMRI evaluation at 6 and 9 months following RT. Acute and late toxicity were defined according to CTCAE v4.0 and RTOG/EORTC scales and QoL was assessed using IPSS, EPIC short-form and UCLA-PCI questionnaires.Dose intensification was feasible in the 30 patients. The median prostate dose was 77.6 Gy (IQR 77.3-78.1) and the median DIL RT dose was 85.2 Gy (IQR 85.0-85.4). With a median follow up of 33 moths (IQR 24.5 - 41.5), all 30 patients remain free of biochemical relapse. A mpMRI complete response was observed in 23 patients during the first post-treatment evaluation performed at 6 months. The remaining 7 patients achieved a complete response in the second mpMRI made at 9 months. Six out of 30 (20%) patients presented acute grade 2 urinary toxicity with no grade 3 acute complications. Acute rectal toxicity was only found in 2 (6.6%) patients (both grade 1). Only late grade 1 urinary (3 cases) and rectal (3 cases) complications were observed, with no grade 2 or more late toxicity.Although preliminary, the present results show that focal dose escalation RT using mpMRI guided VMAT technique is associated with an encouraging local and biochemical control and a safe toxicity profile. This trial was registered on ClinicalTrials.gov, NCT03030625.