Late Toxicity in a Prospective Phase I/II trial of MRI Guided Focal Boost Integrated with HDR Brachytherapy as a Monotherapy for Low and Intermediate Risk Prostate Cancer

Abstract

Increased utilization of magnetic resonance imaging (MRI) provides an opportunity to escalate dose to the dominant intraprostatic lesion (DIL), contributing further evidence for the use of High Dose Rate (HDR) brachytherapy as a monotherapy. We report late toxicity of a prospective Phase I/II trial employing an MRI assisted focal boost integrated with HDR brachytherapy alone for treatment of low and intermediate risk prostate cancer. Eligible patients had low or intermediate risk prostate cancer, IPSS score < 16, were medically operable and had an identified DIL on multiparametric MRI (mpMRI) prior to brachytherapy treatment. Patients were treated with 19Gy delivered in one fraction to the whole prostate. A 0-5mm PTV expansion was applied to the DIL, with a DIL PTV D90 > 23Gy. Toxicity was assessed using CTCAE v.4.0 at 6 weeks, 3, 6, 9, and 12 months post brachytherapy, and every six months thereafter. A total of 62 patients underwent HDR monotherapy including an integrated DIL boost, with a median follow up of 12 months. Median age was 66 years (range 46-80). Eight, 43, and 11 patients had low, low intermediate and high intermediate risk disease. At presentation, median PSA was 6.2 ng/mL (2.2-16.4) and mean prostate volume was 35.8 cc (range 17-55). No patients experienced late Grade 2+ GI toxicity. Late Grade 2 GU toxicity included retention 19% and frequency 4%. Percentage of mild, moderate and severe IPSS scores reported at 12 months follow up were 60%, 36% and 4 %, respectively. Monotherapy of low and intermediate risk prostate cancer with HDR brachytherapy is achievable with minimal late toxicity by utilizing mpMRI to define and escalate dose to the DIL. Long term follow-up is required to determine efficacy of treatment and impact on quality of life.