Correlation of prostate-specific antigen (PSA) levels and survival in men with bone metastatic hormone-refractory prostate cancer (HRPC) and normal alkaline phosphatase (ALK)

Abstract

5140 Background: PSA and ALK are recognized factors for predicting survival in men with metastatic HRPC. However, few studies have evaluated the combined effects of PSA and ALK on survival of patients with metastatic HRPC. Methods: 224 patients treated with chemotherapy for bone metastatic HRPC between 1999 and 2006 were identified from an institutional database. 143 patients had ALK as well as PSA values at start of chemotherapy. There were no statistically significant differences in baseline characteristics (including age, Gleason score, PSA, clinical stage at diagnosis or at the initiation of chemotherapy) between groups with and without available ALK (p>0.05). The primary endpoint was overall survival (OS) after chemotherapy. ALK was dichotomized to normal and abnormal groups based on institutional normal range (38–126 U/L). The effect of PSA was evaluated both as categorical (low, median and high group using the 33%, 66% cut-off values) and continuous values with log transformation in Cox regression. Results: Of 143 eligible patients, median ALK was 159 U/L (range: 52–2,020 U/L); 89 (62%) had elevated ALK. Median PSA at start of chemotherapy was 147 ng/mL; 93 ng/mL in patients with normal ALK and 171 ng/mL in those with elevated ALK. With median follow-up of 30 months after chemotherapy, 93 patients have died. Median OS after chemotherapy was 15.8 (range 0–57) months and was significantly longer if ALK was in the normal range (21.3 vs. 14 months, p=0.005). For the group with normal ALK, median OS was 12.5, 24.5 and 36.9 months for patients with low, median and high PSA, respectively; while there was no effect of PSA on survival if ALK was beyond the normal range (16.5 vs. 11.9 vs. 12.1 months) (p=0.21 for the interaction). In multivariable analysis after adjusting for age, the interaction effect of PSA and ALK on OS was statistically significant (p=0.02). The relative risk due to one unit increase in the value of Ln(PSA) was 0.68 (95% CI: 0.51–0.92) if ALK in the normal range, compared to 1.07 (95% CI: 0.85–1.35) in the group with elevated ALK. Conclusions: ALK was a significant factor in predicting OS for men with bone metastatic HRPC. In patients with normal ALK, a higher PSA was associated with improved survival. No significant financial relationships to disclose.