Radionuclide bone scans are strongly positive in cases of bone involvement of prostate cancer patients, irrespective of whether the lesions are radiologically lytic, mixed or pure blastic (Citrin et al, 1981
). The conventional method to monitor the response of bone metastases to therapy is a combining qualitative assessment of sequential bone scans and bony films with measurement of chemical markers (such as PSA and alkaline phosphatase level). However, to quantitate all bone metastases in patients is a time-consuming task, since patients with metastatic involvement usually have more than one disease site. Several studies have evaluated different ways to quantify the extent of bone involvement during therapy (). The EOD was graded into five categories by visually counting the total number of bone lesions on the bone scan (Soloway et al, 1988
). This method has the difficulty of counting individual lesions when lesions increase in number. It was also recognised that errors would be inevitable because lesions in the ribs are difficult to count and quantify, and assessment of lesions in the pelvis is complicated by the three-dimensional nature of the pelvic bone. In the present study, there was a weak correlation between the %PABS measured using the NIH computer program and the counted number of bone lesions in patients with EOD grades 3 and 4 (greater than 21 bone metastases) compared with grades 1 and 2 (less than 21 bone metastases). Other studies have proposed staging classifications based on visual inspection, whether the lesions on the bone scan occurred with normal uptake, several uptakes or diffuse uptake (Amico et al, 1991
), or according to the negative versus
positive (Chybowski et al, 1991
). These simplified grading systems showed significant associations with survival (Crawford et al, 1989
; Rana et al, 1993
). It is, however, difficult to evaluate serial changes on bone scans after treatment, because the criteria for response and progression vary widely. A simple and reproducible technique was evaluated to measure the 24-h whole body retention (skeletal uptakes) as an objective marker for bony metastases in comparison to clinical outcome (Dann et al, 1987
). This method could be easily automated, but much useful information such as the anatomical information, about which bones are involved or progressing, was lost in this simplified approach. As a result, none of these methods were adopted into routine clinical practice. Some studies have developed a bone scan index (BSI) to more accurately quantify the extent of the skeletal involvement by the tumour. This BSI method is based on a subjective interpretation of the bone scan, in which the fraction of each bone involved is visually estimated (Imbriaco et al, 1998
; Scabbatini et al, 1999
). This technique is a complex method to calculate the sum of the involved area in the 158 bones by summing the fractions times the percentage of the skeleton for each bone, and has shown a variation from 0 to 50% among individual studies in the estimations. Techniques that use computer generated regions of interest (ROI) for regional bone uptake have been attempted in the BSI method (Erdi et al, 1997
). However, expense, long processing times and confusion relating to the exact region to choose made this technique less than ideal.
Definitions of grading systems for the extent of skeletal disease in prostate cancer using a bone scan
In the present study, we used the NIH Image program for measurements of all positive areas on bone scans transferred by manual tracing to a comprehensive map. This method showed a good accuracy for area measurements with a 1.54% CV. The main advantages of the %PABS method are both its simplicity and accuracy in measurements of ROI. However, although these measures correlate with the extent of bone metastases in patients with prostate cancer, the prognostic significance of these measurements has not previously been demonstrated.
The conventional pretreatment risk factors for advanced prostatic cancers were performance status, the presence or absence of bone pain, tumour grade, biochemical parameters such as haemoglobin, alkaline phosphatase and testosterone levels and the EOD grade (Emrich et al, 1985
; Soloway et al, 1988
; Chodak et al, 1991
). PSA is the most widely used tumour marker for diagnosis and follow-up of prostate cancer, but the importance of pretreatment PSA in predicting outcome after therapies was not yet confirmed. In this study, we investigated the relation between survival time and seven potential prognostic factors (age, performance status, tumour grade, PSA, alkaline phosphatase, ICTP and %PABS), using univariate and multivariate regression models. The tumour grade, %PABS, alkaline phosphatase and number of bone lesions were derived from a univariate analysis of prognostic factors for the survival in this series, although the tumour grade, alkaline phosphatase and the number of bone lesions did not remain independent of prognostic value by multivariate analysis. Only the %PABS was a significant predictor of survival after hormonal treatments. Performance status, which was reported as a very strong independent parameter previously (Chodak et al, 1991
), was not a significant predictor. One possible reason for this discrepancy might be in part because of heterogeneity of treatment in the present study. Although the total number of patients in this study was small, the number of patients who had disease death (26 patients, 50%) was quite high, and makes the significance of the data from this study strong relative to its size.