From the Desk of the Editor: “Bone Metastases Matter”

For those of us who are responsible for treating men with metastatic castration-resistant prostate cancer (mCRPC), we’ve all seen the ravages that this disease bestows on its victims – bone pain, weakness, anorexia/weight loss, anemia and other cytopenias and fatigue, profound fatigue.

Normally, we can see this coming – both in terms of the symptoms progressing through the last year or year and a half of life, as well as the tumor burden. Until recently, it has been hard to quantify these factors. For the symptoms, we now have tools that can accurately and longitudinally tract these changes – patient-reported outcome measures that have been validated in this very setting and yet, they are still woefully underutilized.  I will be covering that issue another time in the near future. Today, I want to draw your attention to the other issue – quantifying bone metastases – which was addressed with an article in the May 17th issue of JAMA Oncology, by my colleague at Duke, Andrew Armstrong, MD.

In this feature, Armstrong and colleagues used the Automated Bone Scan Index (aBSI) score in baseline scans of patients on a Phase III study to demonstrate the independent prognostic significance of this assessment in the survival of patients. By way of background, the aBSI is a measure of the percent of red marrow involvement by sclerotic changes on bone scan. The index is non-invasive, inexpensive and easily applied through software analysis. In a subpopulation of patients in whom aBSI was available, there was a huge range in scores at baseline (0-32.60% red marrow involvement) and the baseline score was significantly associated with overall survival (OS) (hazard ratio 1.20; 95% CI 1.14-1.26 p< 0.01). Also, broken down by quartile (lowest to highest) median OS was greatly diminished with each quartile increase, from 34.7, 27.3, 21.7, to 13.3 months, respectively.  Finally, aBSI measure was significantly prognostic for overall survival in patients both in a univariate and multivariate analysis, as well as prognostic for time to chemotherapy and opioid use.

What is remarkable about these results is how easily this tool could be applied to regular practice in identifying patients at risk for complications, as well as early death from prostate cancer.  While we are excited about future imaging modalities in prostate cancer such as Prostate-specific membrane antigen (PSMA)-PET imaging, based upon the imaging’s ease, access and low cost — the bone scan is not going away. The aBSI just makes the bone scan more valuable.

In addition, this data, when broken out in quartiles, can separate survival by several folds, suggesting that it is not simply the presence of bone metastasis (M1) disease that is important, but the extent of disease that matters. We need to think about changing our staging to incorporate measures like this (many tumors use an M1a-c system) to alert clinicians to the need to think about layering therapy in patients with shortened expected survival.

Finally, there is more work to be done with this tool – while the overall disease burden in red marrow is important at baseline, how do changes in red marrow change prognosis? Are two new tiny bone metastases in someone with 20 pre-existing lesions really the same as someone going from two metastases to 12?

Bone metastases matter, my friends, not just their presence but their burden.  

Written by: Daniel J. George, MD, Medical Oncologist, Professor of Medicine, Professor of Surgery, Duke Cancer Institute, Durham, North Carolina