Paraneoplastic elevation of serum alkaline phosphatase in renal cell carcinoma: incidence and implication on prognosis

PURPOSE: We investigated the incidence and prognostic significance of paraneoplastic elevation of serum alkaline phosphatase in patients with renal cell carcinoma. MATERIALS AND METHODS: Clinical data of 365 pathologically proved renal cell carcinoma cases were reviewed. Serum alkaline phosphatase level greater than 100 units per 1., but without obvious conditions that may cause phosphatase elevation, including metastasis to or disease of liver or bone and pregnancy, was regarded as paraneoplastic serum alkaline phosphatase elevation. Survival was evaluated using the Kaplan-Meier method. RESULTS: Of 365 patients 77 (21.1%) had paraneoplastic serum alkaline phosphatase elevation. The respective incidence from stage I to IV cases was 9.9% (16 of 161), 31.9% (15 of 47), 34.3% (23 of 67) and 25.6% (23 of 90). Patients with stage I disease had the lowest incidence but there were no statistically significant differences among stages II, III and IV disease. Of 77 patients with elevated serum alkaline phosphatase 48 had additional paraneoplastic manifestations. The disease specific 5-year survival rate in patients with normal serum alkaline phosphatase was significantly better than in patients with isolated phosphatase elevation, which in turn was better than in patients with multiple paraneoplastic syndromes (70.7 versus 50.5 versus 30.8%). Patients with persistent or recurrent elevation of serum alkaline phosphatase after radical nephrectomy had metastatic lesion or local recurrence. In some patients serum alkaline phosphatase returned to normal after nephrectomy but metastasis developed later without recurrent phosphatase elevation. CONCLUSIONS: Paraneoplastic serum alkaline phosphatase elevation in renal cell carcinoma patients implies an unfavorable prognosis, and additional paraneoplastic syndromes further worsen the prognosis. Recurrent or persistent serum alkaline phosphatase elevation after radical nephrectomy suggests distant metastasis or residual tumor. However, the return of serum alkaline phosphatase to normal does not guarantee cure of the disease. Identification of paraneoplastic serum alkaline phosphatase elevation is valuable in the prediction of outcome and postoperative followup of renal cell carcinoma patients.