BSI includes prognostic information in addition to that obtained from clinical T stage, Gleason score and PSA. Patients with metastatic disease and BSI < 1 showed a 5-year probability of survival of 42% compared to 31% for those with BSI = 1 to 5 and 0% for those with BSI > 5. These findings show that a quantitative measurement of tumour burden in the skeleton can be used to risk-stratify patients more efficiently than only using M-staging based on evidence of the presence or absence of metastatic spread.
The added value of BSI was shown as an increase in C-index from 0.66 to 0.71 when adding BSI to a model including clinical T stage, Gleason score and PSA. This is in agreement with the results presented by Ulmert et al. , where the corresponding increase when adding BSI was of the same magnitude, but from a higher level (0.77 to 0.82). The higher values in the Ulmert study are likely to be due to the fact that death as a result of prostate cancer was used in that study, while all-cause mortality or overall survival was used in this one. The cause of death for the patients was not available in this retrospective study. Furthermore, the common primary end point in large clinical trials exploring the effects of drugs for prostate cancer patients is ‘overall survival’. This study showed the value of BSI in a homogenous group of prostate cancer patients, with those at high risk receiving primary hormonal therapy. In the Ulmert study, low-risk patients were also included and initial treatment was not adjusted for.
The sensitivity for metastatic disease of bone scans is regarded to be high, that is, the number of false-negative cases is low, but some of our M0 patients are probably falsely classified as M0. These patients might at least partly contribute to the higher mortality in the M0 population after 4 years in comparison with the age-matched control group. A follow-up bone scan to validate the BSI from the time of diagnosis could therefore be of value. Change in BSI over time can also contain important information in the M1 group. Dennis et al. recently showed that on-treatment change in BSI was associated with overall survival for patients receiving chemotherapy . Their study also showed that changes in PSA were not associated with survival while adjusting for changes in BSI.
Recently, another study demonstrated the value of BSI in patients with castration-resistant prostate cancer . In a group of 42 patients who underwent taxane-based chemotherapy, reduction of BSI after treatment was associated with longer overall survival. The findings of recent BSI studies show the value of this imaging biomarker in both at the time of diagnosis and at a later stage of the disease.
Based on the results of the present study, BSI can be considered as an informative predictor of patient survival in men with high-risk disease treated with hormonal therapy. BSI can also be of value in clinical trials as an inclusion criterion so that baseline prognosis in treatment and placebo groups can be matched.
The purpose of this study was to generate evidence regarding how BSI can be used to risk-stratify prostate cancer patients by applying an automated software to bone scans - the established method of evaluating skeletal metastases. Bone scans are widely used in both clinical routine and clinical trials, but the methodology has its shortcomings. The radiotracer locates not tumour cells but regions of the skeleton that are actively undergoing tissue repair - a well-known sign of tumour involvement. Future developments in diagnostic imaging may provide improved and more specific methods of analysing skeletal lesions, including three-dimensional methods such as SPECT/CT and PET/CT. At present, bone scan is the dominant clinical method for evaluation of skeletal metastases. Furthermore, prognostic studies based on large patient groups and long follow-up time are not currently available for the new modalities. This type of bone scan study, showing that imaging can be used as a biomarker, will be important in terms of gaining experience, which can also be of value when new imaging modalities become widely used.
This study was based on a fully automated software for calculation of tumour burden in patients with metastatic disease. With this technique, widespread use in clinical routine and clinical trials is possible. Operator-dependent subjectivity in interpretation of bone scans, which has proved to be substantial , is eliminated, and a reproducible analysis can be obtained at different hospitals. The software has proved to be capable of differentiating between malignant lesions and hotspots due to degenerative disease, e.g. by considering whether uptake in the shoulder regions is symmetrical. In this study, only obvious false lesions were manually corrected, e.g. a very large urinary bladder, a urinary catheter attached to a drainage bag or urine contamination. The quality of the software was assessed in a study by Sadik et al. . This study showed that 35 physicians improved their sensitivity to metastatic disease from 78% to 88% using the software for automated analysis of bone scans.