Predictive factors for skeletal complications in prostate cancer patients with hormone refractory disease

Background: Adverse skeletal related events (SREs) are the major causes of quality of life impairment in bone metastatic prostate cancer patients. Methods: We evaluated the frequency of SREs in 200 hormone refractory patients consecutively observed in our Istitution between 1990 and 2003. Baseline parameters were evaluated as potential predictive factors of SREs. Results: SREs were observed in 84 patients (43.0%), namely vertebra collapse in 41 patients (20.5%), fractures in 25 patients (12.5%) and spinal cord compression in 20 patients (10.0%). In 10 patients (5.0%) SREs occurred before the onset of hormone refractory disease. At the last follow-up on August 15 2004, 180 patients (90.0%) had died (median survival 14.5 months). One hundred and five of them (58.3%) without undergoing SREs. In univariate analysis, disease extent in bone (p=.015), bone pain (p=.011), serum alkaline phosphatase (p=.014) and urinary N-telopeptide cross-link (p=.001) directly correlated with a greater chance to develop SREs in the hormone refractory phase of the disease, whereas patient performance status, Gleason score, serum PSA, Hb, serum albumin, serum calcium, types of bone lesions did not correlate. SREs occurring before the onset of hormone refractoriness were significantly associated to the duration of androgen deprivation (p=0.004), whereas SREs occurring in the hormone refractory phase were not. Both disease extent in bone and bone pain were independent variables predicting for the onset of SREs in multivariate analysis. SREs in patients with heavy tumor load in bone and great bone pain were almost double (26% vs 52%, p = 0.016) and occurred significantly earlier [hazard ratio 1.63 (95% Confidence Interval 1.32 - 2.00) p=0.000] than SREs in patients with limited disease extent in bone and low pain. Conclusions: Bone pain and disease extent in bone independently predict the occurrence of SREs in bone metastatic prostate cancer patients with hormone refractory disease. These findings could help the physicians in tailoring to each patient the most appropriate skeletal follow-up, and may prove useful for stratifying patients enrolled in randomized clinical trials testing bone antiresorptive agent