The single most predictive factor in osteosarcoma is the presence or absence of detectable metastatic disease at presentation. As mentioned, the survival rate for patients who have metastases at the time of presentation is between 10 and 20 % [1, 2]. Those who present with bone or skip metastases fare even worse [3, 4]. The degree of tumor necrosis after neoadjuvant chemotherapy is also an important prognostic factor. Patients who have tumors with a good response to chemotherapy (>90 % tumor necrosis) have a considerably better long-term survival rate than those who have tumors with a poor response (<90 % tumor necrosis) [5–7]. The response to chemotherapy is commonly assessed by histological analysis, although it is difficult to evaluate the chemotherapeutic effects before tumor excision. Miwa et al. evaluated the impact of various radiological examinations on overall survival and event-free survival. They concluded that 99mTc-MIBI scintigraphy and combined radiological score (CRS) could be considered as significant predictor of overall survival and event-free survival [8]. Large tumor size has been implicated as a negative prognostic indicator in several studies; however, inconsistent methods of determining size in these studies make it difficult to ascertain its true influence. Other poor prognostic variable was patient’s age at diagnosis. The prognosis of elderly patients was generally considered to be worse compared to those of the young patients. Iwata et al. conducted the multi-institutional retrospective study to investigate clinical features and prognostic factors in patients older than 40 years with osteosarcoma. They demonstrated the distinct clinical features, such as the high incidence of truncal tumors or metastasis at diagnosis, in patients older than 40 years with osteosarcoma. Additionally, prognostic factor analyses revealed that tumor site, metastasis at diagnosis, definitive surgery, and surgical margins were significant prognostic factors, whereas chemotherapy did not influence survival [9]. A tumor located in the pelvis, proximal part of the femur, or proximal part of the humerus also appears to be indicative of a poor prognosis [10].

One of the most interesting topics in cancer therapy is that of anti-angiogenesis. Very little work on sarcomas has been done in this field. Anti-angiogenic agents have been shown to inhibit tumor growth and cause tumor regression in mouse models [17]. There are currently many anti-angiogenic agents being tested in Phase I and II clinical trials of their effects on human cancers. Two of the targets of these trials are vascular endothelial growth factor and its receptors. Kaya et al. recently demonstrated expression of vascular endothelial growth factor in 17 (63 %) of 27 osteosarcomas [18]. They also correlated this expression with a high prevalence of pulmonary metastasis, suggesting that expression of vascular endothelial growth factor may play a role in the metastatic cascade of osteosarcoma [18]. Kaya et al. also evaluated the prognostic significance of the serum levels of vascular endothelial growth factor (VEGF) in predicting the survival of patients with osteosarcoma prospectively. Patients with a serum VEGF >1000 pg/ml had significantly worse survival than those with a level <1000 pg/ml (p = 0.002). They concluded that serum VEGF level might be useful in predicting the prognosis for survival in patients with osteosarcoma [19]. It may also become a treatment target, and anti-angiogenic therapy using antivascular endothelial growth factor antibody and a vascular endothelial growth factor receptor inhibitor is expecting to offer a potentially useful strategy for lung metastasis from osteosarcoma. This was supported by the experimental research work by Tanaka et al. They demonstrated that disruption of the vascular barrier and transendothelial migration of syngeneic mouse spontaneous highly metastatic osteosarcoma cell line LM8 is dependent, at least one part, on VEGF [20]. They also demonstrated that daily oral administration of pazopanib reduced the rate and size of pulmonary metastasis in vivo [20].