Stereotactic Body Versus Hypofractionated Radiation Therapy for Local Control of Prostate Cancer Bone Metastases

Abstract

To compare the rate of radiographic in field failure (IFF) for prostate cancer bone metastases treated with single fraction stereotactic body radiation therapy (SBRT) and hypofractionated radiation therapy (HRT), and secondarily describe the rate of subsequent distant failure (DF). An institutional, retrospective review was conducted of all patients with prostate cancer receiving RT to bone metastases between January 2013 and May 2017. Patients were excluded if less than 6 months of clinical and imaging follow-up was available. IFF was defined as any increase in the size and/or radiotracer avidity of the treated lesion, subsequent use of a secondary local salvage therapy to the treated site, or the appearance of a new lesion within the initial 50% isodose line. DF, defined as new metastatic disease following RT, was a secondary outcome. The cumulative incidence of IFF and DF was determined using the Fine-Gray method with death as a competing risk. Hazard ratios (HR) for single variable associations with outcomes were calculated using the Cox model and a P value of 0.05 was set to determine significance. A total of 201 patients with 249 metastases (191 SBRT, 58 HRT) with a median follow-up of 2.2 (IQR 1.2-3.0) years were analyzed. Patients treated with SBRT more frequently had 1-3 metastases compared to those receiving HRT (85% vs 40%, P<0.0001). The presence of castrate resistant disease was not significantly different between the SBRT and HRT groups (41% vs 35%, P=0.39). The SBRT prescription dose ranged from 16 to 24 Gy in a single fraction, with most receiving 18 (46%) or 20 (47%) Gy. HRT was mainly 8 Gy in 1 fraction (57%) or 20 Gy in 5 fractions (41%). Imaging follow-up was primarily with 11C-choline PET/CT (79%), technetium 99m-MDP bone scan (10%), or CT scan (5%). The one and three-year IFF rates were 34% (95% CI 20-46) and 53% (34-67) for lesions treated with HRT compared to 5% (1.4-7.5) and 13% (7-19) in those treated with SBRT. On single variable regression, the HR for IFF with HRT compared to SBRT was 6.8 (3.7-12.5; P <.0001). No other variables assessed, including Gleason score, castrate resistant disease status, or anatomical location of metastasis were associated with an increased risk of IFF (P >0.05). There was no difference in DF for patients treated with HRT compared with SBRT [3-year cumulative incidence estimate 94% (77-98) vs. 82% (75-88); HR 1.33 (0.97-1.81), P=0.08]. Single fraction SBRT at doses ≥ 16 Gy is an effective means of local therapy and significantly improves radiographic IFF compared to HRT in prostate cancer patients with bone metastases. In this large cohort of patients, local control using SBRT was 95% and 87% at one and three years respectively. The subsequent risk of DF was high. Thus, optimizing patient selection and multidisciplinary management of local and systemic therapies remains essential.