MR-Guided HDR Brachytherapy Boost in Localized Prostate Cancer - Results of a Phase II Trial.

Abstract

Dose escalation in localized prostate cancer using brachytherapy combined with external beam radiation (EBRT) has demonstrated improved biochemical control compared to EBRT alone. However, ultrasound guided LDR brachytherapy might be associated with increased GU toxicity. We report the results of a prospective study of MR-guided HDR brachytherapy (MRgHDR) in combination with EBRT for localized prostate cancer. Intermediate- (IR) and high-risk (HR) prostate cancer patients were eligible. Patients received either 15Gy single fraction or 10Gy x 2 fractions using MRgHDR technique, followed by EBRT (37.5 Gy, [prostate only] -IR or 45-46 Gy - [prostate + pelvic nodes] -HR). Toxicity (CTCAE v4) and HRQoL (EPIC) were recorded at 1, 3 and 6 months, then at 1, 2, 3, and 5 years. Androgen deprivation therapy (ADT) was used according to the appropriate disease risk category. Biochemical failure was defined according to Phoenix definition (nadir+2). From 2010-2018, 120 patients were enrolled, 53 (44%) had IR and 67 (56%) had HR disease. Median age was 69 years (range, 46-78), median PSA was 12.1 ng/ml (3.2-148). ADT was used in 84 (70%) of patients, of whom 51 (60%) patients received <1 year and 33 (40%) received >1 year of ADT. A single fraction of 15Gy was given to 94 patients (78%) and the remaining 26 patients (22%) received 10Gy x 2 fractions. EBRT dose was 37.5Gy in 52 (43%) patients while 67 (56%) received 45-46Gy. One patient received only the first fraction of 10Gy, declined the second fraction and subsequently received 60Gy EBRT to the prostate. The median follow up was 58 months (11-134). Overall, 5-year biochemical control was 90% while it was 95% and 86% for IR and HR, respectively. At 5 years 7% patient had nodal or distant relapse or both. While the 5-yr distant control rates were 95% and 91% in the IR, HR, respectively. Acute grade ≥2 GU and GI toxicity was 6.7% and 5% respectively. Acute toxicity trended back to baseline by 6 months in all patients except one. Late grade ≥ 2 GU and GI worst toxicity was seen in 10% and 4.2%, respectively. As with acute toxicity, late toxicity tended to improve over time. Only one patient experienced severe toxicity (Grade 3 GU - frequency) at 6 months but subsequently this resolved. HRQol will be reported separately. MRgHDR brachytherapy boost in conjunction with EBRT provides comparable biochemical outcomes compared to the literature. Severe toxicity rates were minimal. Further follow-up will determine if these outcomes are sustained.