Reassessment of alkaline phosphatase as serum tumor marker with high specificity in osteosarcoma

The goal of this study was to reassess serum alkaline phosphatase (ALP) as tumor marker in osteosarcoma. We retrospectively examined serum ALP levels at diagnosis, every therapeutic step (neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy), metastasis, and follow-up and analyzed the role of ALP as tumor marker in 210 osteosarcomas. The diagnostic performances of ALP were validated with pathology-proven 899 other primary bone lesions. Elevated ALP at diagnosis was associated with inferior overall survival (OS) (Log Rank P < 0.001) and disease-free survival (Log Rank P = 0.005) and independently significant for OS in multivariate analysis (hazard ratio [HR]=2.12, P = 0.032). During therapy, the ALP level significantly changed according to therapeutic steps (P < 0.001 for patients ≥15 years old, P < 0.001 for patients <15 years old) and survival (P = 0.015 for ≥15 years, P = 0.002 for <15 years), and the response of ALP to therapy and survival were associated (P = 0.042 for ≥15 years, P = 0.036 for <15 years). Initial ALP level was linearly correlated with tumor burden (total tumor volume; P = 0.016 for ≥15 years, bone tumor volume; P = 0.012 for ≥15 years). The sensitivity and specificity of ALP on diagnosis were 53.2% (95% Confidence Interval [CI]: 0.475-0.586) and 90.1% (95% CI: 0.888-0.913). The sensitivity of ALP on metastasis was 53.2% (95% CI: 0.431-0.624), and the specificity was 78.2% (95% CI: 0.720-0.839) at15 months postoperative and 90.0% (95% CI: 0.824-0.952) at 3 years postoperative. Serum ALP was found to be a valuable tumor marker with high specificity in osteosarcoma.