Bone scan index: a quantitative treatment response biomarker for castration-resistant metastatic prostate cancer

Abstract

Purpose: There is currently no imaging biomarker for metastatic prostate cancer. The bone scan index (BSI) is a promising candidate, being a reproducible, quantitative expression of tumor burden seen on bone scintigraphy. Prior studies have shown the prognostic value of a baseline BSI. This study tested whether treatment-related changes in BSI are prognostic for survival and compared BSI to prostate-specific antigen (PSA) as an outcome measure.

Patients and methods: We retrospectively examined serial bone scans from patients with castration-resistant metastatic prostate cancer (CRMPC) enrolled in four clinical trials. We calculated BSI at baseline and at 3 and 6 months on treatment and performed univariate and bivariate analyses of PSA, BSI, and survival.

Results: Eighty-eight patients were scanned, 81 of whom have died. In the univariate analysis, the log percent change in BSI from baseline to 3 and 6 months on treatment prognosticated for survival (hazard ratio [HR], 2.44; P = .0089 and HR, 2.54; P < .001, respectively). A doubling in BSI resulted in a 1.9-fold increase in risk of death. Log percent change in PSA at 6 months on treatment was also associated with survival (HR, 1.298; P = .013). In the bivariate analysis, change in BSI while adjusting for PSA was prognostic at 3 and 6 months on treatment (HR, 2.368; P = .012 and HR, 2.226; P = .002, respectively), but while adjusting for BSI, PSA was not prognostic.

Conclusion: These data furnish early evidence that on-treatment changes in BSI are a response indicator and support further exploration of bone scintigraphy as an imaging biomarker in CRMPC.

Fig 1.

(A) Visualization of the bone scan index (BSI). The area of active marrow is shown in red, which is usually the primary distribution of metastatic disease in prostate cancer. The BSI is calculated first by determining the percentage of each bone that is involved by the tracer in relationship to the total skeletal mass, as determined from reference man. This procedure is done for every single bone, and all of the individual percentages are summed to arrive at a single number that represents the total tumor burden as a percentage of the total skeletal mass. Notably, approximately 40% of the skeletal mass is active marrow. (B) Typical sequence of bone scans and BSI calculations for a patient with metastatic castration-resistant prostate cancer. The percentage of total skeletal mass involved by the tracer progresses from 0% to 0.59% to 7.7% and after treatment falls to 5.4%. MDP, methylene disphosphonate; Tc-99m, technetium-99 metastable nuclear isomer.

Fig 2.

Flow chart detailing the available patient cohorts for the baseline, +3 months on-treatment, and +6 months on-treatment analyses. Five patients had missing data at baseline. There is a decrease in sample size from baseline to +3 months to +6 months as patients dropped out of their clinical trials in which the imaging was performed because of disease progression (manifested primarily by an increase in prostate-specific antigen), drug toxicity, or concurrent disease. Alive or dead indicates the patients' vital status at the time the analysis was performed.

Fig 3.

Nonparametric estimation of median time to death against on-treatment (A, B) bone scan index (BSI) and (C, D) prostate-specific antigen (PSA) changes. Each “x” symbol represents a death event, and each “o” symbol represents a patient still alive at the time of analysis.