In this report, we describe a method for quantitative bone scan interpretation (the Bone Scan Index or BSI) in advanced
prostate cancer. The BSI estimates the fraction of the skeleton that is involved by
tumor, as well as the regional distribution of the
metastases in the bones. The purpose of this report is to describe the development and validation of this method in terms of reproducibility and the application of BSI for determining extent of disease and monitoring
disease progression. We analyzed 263 bone scans from 90 patients being studied under four protocols at Memorial Sloan-Kettering
Cancer Center for progressive,
androgen-independent
prostate cancer (
AIPC), who had bone scans as a part of their work-up. We determined: (a) the intraobserver and interobserver variability of the BSI; (b) the comparison between a change in BSI and
prostate-specific antigen (PSA); (c) the regional distribution of bony
metastases in early stage D
prostate cancer (<3% skeletal involvement); and (d) the rate of growth of bony
metastases from
prostate cancer. A cube root transformation of the percentage of involvement of the entire skeleton was used to stabilize the variance over the entire span of values (0-60%
tumor involvement). The range of interobserver variability between readers was 0.2-0.5 times the cube root of the BSI (69 scans, 18 patients). Intraobserver variability was minimal when the same reader read the same scans after a 2-year interval, showing a correlation coefficient of 0.97 (reader 1) and 0.99 (reader 2), P < 0.001. There was a parallel rise in the BSI and the PSA in 24 patients (105 scans) treated for
AIPC with
hydrocortisone followed by
suramin at PSA relapse (Pearson's moment correlation, 0.71). In a group of 27 patients with limited bone involvement by
AIPC (i.e., <3% BSI), the distribution of early
metastases was not random within the skeleton but was distributed in the central skeleton in a manner that matched the distribution of the normal adult bone marrow. Also, in a group of 21 patients (62 scans), the change in BSI as a function of time after diagnosis was explored graphically. The progression of bone scan changes in
AIPC, from early involvement (<3%) to late involvement, was fitted to a Gompertzian equation. It showed a rapid exponential growth phase, with an estimated
tumor doubling time of 43 days when the BSI was 3.3%. The change in BSI rapidly approached a more gradual slope as the percentage of skeletal involvement increased. The BSI provides a reproducible new parameter for quantitative assessment of bone involvement by
AIPC. These results suggest that the BSI will be useful for stratifying patients entering treatment protocols for extent of
tumor involvement of bone. Although further study is necessary, serial bone scan BSI appears capable of quantifying both the progression of bony involvement by
tumor as well as the response to treatment.