Zürich experience with preoperative, high dose methotrexate-containing chemotherapy in patients with extremity osteosarcomas (OSA)

From 1979 to 1990, 37 patients with extremity osteosarcomas, 22 of them males and 15 females, median age 19 years, received pre- and postoperative chemotherapy. The period of observation, calculated from after the primary operation, ranged from 1–114 months, median 25 months. After preoperative chemotherapy, 9 (24%) underwent a primary amputation, in 28 (76%) a limb salvage procedure was possible. 4/29 (14%) later developed local recurrences, metastases were diagnosed in 8/9 amputees and 5/28 after limb-sparing surgery. The five-year disease-free and overall survivals after amputation are 11% and 33%, respectively, compared to 68% and 75%, respectively (p=0.001 and 0.018, respectively, for long rank). Results of histologic assessment after preoperative chemotherapy are of significant prognostic impact. The earlier prognostic groups of 0%–49% necrosis versus 50%–100% necrosis were statistically no longer suitable for distinguishing useful prognostic groups. In this second analysis, patients with 0%–79% necrosis versus 80%–100% necrosis had 5-year disease free survivals of 81% versus 44% (p=0.032) and 5-year overall survivals of 88% versus 56% (p=0.07 log rank). In summary, 24% of our patients with extremity osteosarcomas, most of them with large primaries close to joints, had to undergo primary amputation and had only a 33% 5-yr-survival, whereas limb salvage procedures with pre and postoperative chemotherapy were associated with a 5-yr survival of 75% and thus had no adverse impact. Careful selection of patients for successful management of osteosarcomas is important; necrosis of 80% and more after preoperative chemotherapy is a prerequisite for a favourable outcome.