Preliminary Results Of MR-Guided Brachytherapy Boost To External Beam Radiotherapy For Intermediate And High Risk Prostate Cancer

Abstract

To determine if the superior soft tissue differentiation on magnetic resonance imaging (MRI)-guided high dose rate (HDR) brachytherapy (BT) planning increases the therapeutic index of BT boost intensification strategies for localized prostate cancer (PCa), we report the early results of a prospective study of HDR BT boost using a MRI only workflow. Eligible patients (pts) included intermediate- (IR) and high-risk (HR) PCa. Treatment consisted of whole gland boost with HDR BT (15Gy single, or 10Gy two fractions), using MRI alone for BT needle insertion and treatment planning (technical details previously described). Where applicable, the second fraction was usually delivered during week 3 or 4 of external beam radiotherapy (EBRT). EBRT to prostate +/- pelvic nodes, as clinically indicated, commenced within 1 week following BT. EBRT was planned using intensity modulated radiotherapy. Pts also received androgen deprivation therapy (ADT) as per their risk status. Follow-up assessments included CTCAE (v4)-graded toxicity, EPIC questionnaire, and PSA at baseline, 1, 3, 6, 12, 24, 36, and 60 months. Between 2010 and 2018, 120 pts were enrolled and had >6-month follow-up. Median age of pts was 69.5 years (47 – 78 years); 53 (44 %) pts had IR, and 67 (56 %) pts had HR PCa. The median baseline PSA was 12.3 ng/ml (3.2 – 148 ng/ml). Overall, 87 (73%) pts had ADT of whom 56 (64%) had HR disease. Median duration of ADT was 2 years. A total of 144 BT fractions were completed with 22 (18%) pts receiving 2 x 10Gy and 97 (81%) pts received 1 x 15Gy. 43% of pts received subsequent EBRT 37.5Gy/15# to prostate alone. 57% of pts received pelvic and prostate EBRT with majority receiving 46Gy/23# (40 – 60Gy). The median PTV V100 was 95% (91.5 – 99.1%). Median urethra D0.5cc, rectum D0.5cc and bladder D0.5cc were 122% (106 – 166%), 83% (62 – 93%) and 90% (63 – 124%). After a median follow-up of 36 months (6 – 109 months), the overall 3-year biochemical recurrence (Phoenix definition) free rate was similar between IR and HR pts at 94%. At last follow up, 1 patient had seminal vesicle recurrence, 6 (5%) had developed metastatic disease confirmed radiologically. EPIC GU, GI, and sexual domain scores showed mean declines from baseline at 1-month post treatment and then gradual recovery. GU scores returned toward baseline levels by 24 months, GI by 36 months. Sexual domain demonstrated minimal recovery by 36 months follow up. Late CTCAE grade 2/3 GU, GI and sexual toxicities occurred in 22%, 6%, and 5% of pts, respectively. There were 6 (5%) CTCAE grade 3 adverse events, 3 sexual and 3 GU, but no grade 4 toxicity. Early results of MR-guided BT boost in PCa is associated with acceptable biochemical control, toxicity and quality of life. Late grade ≥2 toxicities were comparable to other studies and GU/GI quality of life returned to baseline by 3 years. Further follow up will determine long-term outcomes.