US-Planned HDR Prostate Brachytherapy Boost: Acute and Late Toxicity

Abstract

HDR prostate brachytherapy has been combined with external beam (EBRT) for over 2 decades, using a wide range of dose and fractionation schedules. Complications such as urethral strictures are reported from 2-30%. We evaluate acute and long term urinary and bowel toxicity in our first 5 years’ experience. From 06/2011 to 05/2016, 123 patients with upper tier intermediate and high risk prostate cancer were treated by 192-Ir HDR brachytherapy combined with EBRT in 3 consecutive IRB-approved clinical trials with data collected prospectively. EBRT with fiducials for image-guidance followed US-planned HDR BT within 7 days (46Gy/ 23: 81% 3DcRT, 19% IMRT/VMAT). Initially 20Gy/2 in 2 separate implants was prescribed (42%), but later 15Gy/ 1 (58%). HDR planning constraints were prostate V100 ≥98% and V125: 55-62%, urethra Dmax <115% and rectal D1cc ≤70%. Tumor stage was T1c: 16%, T2: 77% and T3: 7%. Gleason score was 7 in 68%; 8-10 in 32%. Median PSA was 10.1 (range: 1.7-35.8). 65% were upper tier intermediate risk; 35% high risk. 54% had androgen ablation (< 6 mos: 7.5%, 6 mos: 21.5%, 9-12 mos: 60%). Median prostate volume at HDR was 35cc (range: 14-82) Toxicities were graded using CTCAE, V3.0. Median follow-up is 24.3 mos (range: 7– 69) but differed between the 2 cohorts, being 43 mos for 20 Gy/2 (range: 23-69) and 17 mos for 15 Gy/1 (range: 7-43).Catheterization was required post implant in 3.3% and in all cases consisted of clean intermittent self-catheterization for 1-5 weeks during the EBRT that immediately followed the HDR, the majority in the 15 Gy/1 cohort (3 of 4). The average prostate volume for these patients was 48cc vs 37cc for all patients. Acute Grade 1 GU toxicity occurred in 52%, G2 in 13%, and G3 in 3.3%. Acute Grade 1 GI toxicity occurred in 43%, G2 in 5.7%, with no G3 or G4 toxicity. Late GU toxicity was Grade 1: 40%, G2: 7.3%, and G3: 4.0 %. Of these, late Grade 1 hematuria was reported by 5.7% and Grade 2 in 1.6%. Urethral strictures occurred in 3.2% (n=4) after an average of 2.8 years (range: 2.2- 3.5 years), equally divided between the two fractionation schemes. All 4 have been effectively managed, 3 with a single visual internal urethrotomy and one with dilatation. Late GI toxicity was Grade 1: 14.6%, G2: 7.3%, and G3: 3.2%. One patient had a colostomy for a sigmoid stricture outside the HDR radiation volume. Rectal bleeding occurred in 11 patients (8.9%), Grade 1 in 7 patients, and G3 in 4, after an average of 17.5 mos (range 3-35). For G3 bleeding, 75% received 15Gy/ 1. The average rectal D1cc for all patients was 61.5% (range 51%-71%) and was not different for those with rectal bleeding (p=0.43). US-planned HDR brachytherapy as 2 fractions of 10 Gy or a single 15 Gy combined with EBRT is well tolerated with low risk of late toxicities. Urethral strictures were seen in 3.2% and grade 3 rectal bleeding in 3.2%. A single 15 Gy is convenient and cost-effective but observed toxicity may increase with longer follow up as only 50% have reached the median time for toxicity development.