Biochemical Failure and Toxicity of Magnetic Resonance Imaging Dose Painting to Dominant Intraprostatic Lesion in Prostate High Dose Rate Brachytherapy

Abstract

Multiparametric magnetic resonance imaging (mpMRI) is increasingly being used in high dose rate (HDR) brachytherapy treatment planning. Its enhanced soft tissue contrast over conventional computed tomography increases the ability to identify the dominant intraprostatic lesion (DIL) and enables focal boosting using HDR brachytherapy. This can have important implications for adjacent organs at risk. We therefore investigated the acute and late toxicities reported within our institutional experience with this approach.We compiled 4 cohorts of prostate cancer patients treated with mpMRI dose painted HDR brachytherapy (either as a boost or as monotherapy on clinical trial) between December 2014 and October 2018. Salvage brachytherapy was excluded. Three of the cohorts were from prospective clinical trials (MARS, HDR monotherapy and SPARE). For the MR-HDR boost cohort, pertinent demographic, clinical and dosimetric information were extracted from patients' medical records. Descriptive statistics were used to summarize baseline data. Toxicities experienced were coded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The Nelson-Aalen estimator method using 95% confidence intervals was used to assess the cumulative incidence of biochemical failure (BCF; using the Phoenix Failure definition) and the cumulative incidences of grade 2 or higher toxicity.144 patients with a mean age (65.6 ± 6.7 years), follow-up (55.7 ± 15.0 months) and baseline PSA (9.7 ± 8.3 ng/mL), with predominantly cT2a (32.6%) and Gleason 7 (3+4; 62.0%) disease, were included in the final analysis. Fifteen patients treated with MR-HDR boost were followed elsewhere so no toxicity data were available at time of analysis. All risk groups were represented: low (10.4%), favorable (27.8%) and unfavorable intermediate (36.8%), and high (25.0%). 25/137 (18%) experienced BCF with cumulative incidence rates of 20.6% at 5-years. A total of 41/129 (32%) patients experienced any grade 2+ GU (1 G3) and 7/129 patients (5.4%) experienced any grade 2+ GI (0 G3) toxicity. The cumulative incidence rates at 5-years were 33.2% for GU and 5.7% for GI, respectively. Neither BCF or toxicity (GU or GI) was significantly different between treatment groups.Dose escalation to the DIL using mp-MRI dose painted HDR brachytherapy appears to be feasible, safe and well-tolerated. Further follow-up and investigation are warranted to determine whether MR-HDR improves outcomes compared to standard non-MR-HDR brachytherapy.