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

Summary 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.