Background: mCRPC is a bone dominant lethal disease. A validated endpoint in mCRPC trials is bone scan progression, which is semi-quantitative and rely on the appearance of new lesions as proposed by the PCWG. The validated automated bone scan index (BSI) quantifies the bone tumor burden as the fraction of total skeletal weight. To build on the current definition of disease progression, we sought to compare the association of time to progression with overall survival (OS) using PCWG criteria and BSI increase. Methods: mCRPC patients (pts) enrolled on trials of agents targeting androgen-receptor (AR) were assessed. Pts were required to have a raw bone scan image for BSI analysis concurrent with disease assessments. The EXINI automated computing platform generated the BSI values. Thresholds for the absolute and relative increase in BSI from 1st follow-up (≤12 weeks) were explored for the time to BSI progression. The association with survival time was computed for each threshold defined time to BSI progression. Kendall’s Tau, derived from the Clayton copula, was used to associate time to BSI progression with survival time, where both endpoints may be censored. Results: A total of 257 pts were assessed, of whom 169 had raw bone scans images needed for the BSI analysis. 90 pts (53%) met progression by PCWG criteria, the association between the time to PCWG progression and OS was 0.52. The association between time to BSI progression and OS was comparable to the PCWG progression when the absolute increase in BSI was 0.6 or more (table below). Conclusions: Progression in bone can be expressed as a single quantitative metric that describes the increase in total disease burden while retaining the same association that PCWG has with OS. These data represent the first steps to a quantitative expression of bone disease progression as a clinical trials endpoint.