Background. It is known that many patients with osteosarcoma have high serum alkaline phosphatase (SAP) levels. The prognostic significance of this finding, however, is still controversial. Methods. The pretreatment SAP levels of 656 patients with osteosarcoma of the extremities (107 metastatic and 549 localized at presentation) were examined to evaluate whether the enzyme levels had a clinical value in predicting the course of the disease. Results. The percentage of patients with increased SAP levels was significantly higher in the metastatic group than in the group of patients with localized disease (91.5% versus 61.3%; P > 0.001). In the latter group, treated with adjuvant and neoadjuvant chemotherapy, the relapse rate was significantly higher in patients with elevated pretreatment SAP levels than in those with normal levels (55.1% versus 26.4%; P > 0.001). Among patients with elevated SAP levels, the percentage of relapses was higher in patients with high levels of the enzyme in comparison with patients with moderately elevated values (66.4% versus 47%; P > 0.05). After treatment, SAP levels almost always return to normal values, and a correlation between postoperative levels of the enzyme and prognosis could not be made. Conclusions. These data demonstrate that in osteosarcoma of the extremities, pretreatment SAP levels have a prognostic value and they should be considered when comparing the results achieved with different therapeutic protocols and in planning new randomized clinical trials.

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The relationship between the serum concentration of methotrexate and the prognosis has been studied in 108 patients with osteosarcoma of the extremities treated from September 1986 to December 1989 at the Chemotherapy Department of Rizzoli Hospital. The protocol of neoadjuvant chemotherapy included high doses of methotrexate (HDMTX) adriamycin, cisplatinum, ifosfamide and VP-16. After a median follow-up of 40.4 months (range 24-62), 84 (77.7%) of the patients studied remained continuously disease-free (CDF) and 24 relapsed. Significantly higher mean serum MTX concentrations were observed in the patients who remained CDF (669.5 mumol/l) than in the patients who relapsed (571.9 mumol/l) (p < .004). The breaking point of prognostic significance for the serum MTX levels seems to be 700 mumol/l. In fact, according to the mean MTX concentrations, the patients with less than 700 mumol/l showed a significantly lower disease-free survival than the patients with higher mean MTX concentrations (68.12% vs 94.87% p < .0013). The distribution of prognostic variables between the two groups was the same in terms of site and histological type of tumor and alkaline phosphatase serum levels at diagnosis. In the group which had more than 700 mumol/l MTX, a higher percentage of good histological response after primary chemotherapy was observed. This is probably independent from the MTX because no significant preoperative MTX serum levels between good and partially responding patients were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

In 163 patients with osteosarcoma of the extremities treated with adjuvant chemotherapy, serum alkaline phosphatase (SAP) levels were evaluated before treatment and successively closely monitored in an attempt to determine whether serum levels of this enzyme had clinical value in predicting the course of the disease. Of 121 patients with elevated preoperative SAP levels, 78 (64%) recurred. Of 42 patients with normal preoperative SAP levels, only 8 (19%) recurred (P less than 0.00001). Of the 140 patients locally treated with amputation, SAP returned to normal values in 77 patients; 46 of these (59%) relapsed. Of the 21 patients whose SAP remained elevated after amputation, all but 2 relapsed (90%). Among 119 patients with normal postoperative values of SAP, at the time of relapse SAP resulted elevated in 22 of 41 patients (53%). These data confirm that in osteosarcoma, preoperative SAP levels have a definite value in establishing the prognosis and that posttreatment follow-up examination should include SAP determination, since persistent elevated or increasing values herald the appearance of a recurrence.