Assessing Therapeutic Response to Radium-223 with an Automated Bone Scan Index among Metastatic Castration-Resistant Prostate Cancer Patients: Data from Patients in the J-RAP-BSI Trial

Abstract

To evaluate the usefulness of change in the automated bone scan index (aBSI) value derived from bone scintigraphy findings as an imaging biomarker for the assessment of treatment response and survival prediction in metastatic castration-resistant prostate cancer (mCRPC) patients treated with Ra-223. This study was a retrospective investigation of a Japanese cohort of 205 mCRPC patients who received Ra-223 in 14 hospitals between July 2016 and August 2020 and for whom bone scintigraphy before and after radium-223 treatment was available. Correlations of aBSI change, with changes in the serum markers alkaline phosphatase (ALP) and prostate-specific antigen (PSA) were evaluated. Additionally, the association of those changes with overall survival (OS) was assessed using the Cox proportional-hazards model and Kaplan-Meier curve results. Of the 205 patients enrolled, 165 (80.5%) completed six cycles of Ra-223. Following treatment, ALP decline (%ALP < 0%) was noted in 72.2% (148/205), aBSI decline (%aBSI < 0%) in 52.7% (108/205), and PSA decline (%PSA < 0%) in 27.8% (57/205). Furthermore, a reduction in both aBSI and ALP was seen in 87 (42.4%), a reduction in only ALP was seen in 61 (29.8%), a reduction in only aBSI was seen in 21 (10.2%), and in both aBSI and ALP increasing/stable (≥0%) was seen in 36 (17.6%) patients. Multiparametric analysis showed changes in PSA [hazard ratio (HR) 4.30, 95% confidence interval (CI) 2.32-8.77, p < 0.0001], aBSI (HR 2.22, 95%CI 1.43-3.59, p = 0.0003), and ALP (HR 2.06, 95%CI 1.35-3.14, p = 0.0008) as significant prognostic factors for OS. For mCRPC patients treated with Ra-223, aBSI change is useful as an imaging biomarker for treatment response assessment and survival prediction.

Keywords: 223Radium-dichloride; bone scintigraphy; castration-resistant prostate cancer (CRPC); overall survival; treatment response.

Figure 1

Representative bone scintigraphy findings of a 68-year-old male. Illustration of change in automated bone scan index (aBSI) after six cycles of Ra-223. Red color represents hotspots detected using the BONENAVI software package and included in aBSI assessment.

Figure 2

Correlation between changes in serum markers ALP and PSA, and rate of aBSI change. aBSI change showed (a) a very weak but significant correlation with ALP change (r = 0.17, p = 0.017), and (b) a weak but significant correlation with PSA change (r = 0.33, p < 0.0001). (c) ALP change showed a weak but significant correlation with PSA change (r = 0.27, p < 0.0001).

Figure 3

Kaplan–Meier curve findings showing overall survival (OS) following initiation of Ra-223 therapy based on change of (a) ALP, (b) PSA, and (c) aBSI. (a) Median OS of 148 patients with ALP decline was significantly longer than that of 57 patients with ALP increase/no change (22.6 vs. 15.8 months, p = 0.015). (b) Median OS of 57 patients with PSA decline was significantly longer than that of 148 patients with PSA increase/no change (32.5 vs. 16.8 months, p < 0.001). (c) Median OS of 108 patients with aBSI decline was significantly longer than that of 97 patients with aBSI increase/no change (27.1 vs. 16.2 months, p < 0.001). (d) Median OS of the 43 patients with declines in both aBSI and PSA (33.3 months) was significantly longer (p < 0.001) than that of the 79 patients with a decline in only aBSI or PSA (20.5 months) and that of the 83 patients with aBSI increase/no change and PSA increase/no change (15.2 months).