A number of factors influence prognosis:
Local versus Metastatic
Prognosis for localized disease: EFS about 70% at 3 years (JCO 2005 Mar;23(9):2004-11).
The prognosis for patients with metastatic disease appears depends on
- Number of metastases
- Surgical resectability of the metastatic disease.
Patients with metastasis to other bones distant from the primary tumor experience roughly 10% event-free and overall survival.
In patients with metastases confined to lung have an EFS about 45%. In lung prognosis appears more favorable for patients with fewer pulmonary nodules and for those with unilateral rather than bilateral pulmonary metastases
- Presents with symmetrical, metaphyseal lesions
- May be difficult to decide which is the primary lesion
- Multifocal bone disease at presentation has an extremely poor prognosis
- No patient with synchronous multifocal osteosarcoma has ever been reported to be cured
- Systemic chemotherapy and aggressive surgical resection may achieve significant prolongation of life
Pathology (parosteal and intraosseous well differentiated) have a favorable prognosis.
Response to chemotherapy
Patients with more than 90% necrosis in the primary tumor after induction chemotherapy have a better prognosis than those with less necrosis (75-80% versus 45-50%).
The degree of necrosis in the primary tumor after induction chemotherapy remains prognostic in metastatic osteosarcoma.
Huvos response classification widely referred to although not used in all groups:-
Histologic Response of Osteosarcoma to preoperative chemotherapy:
Little or no effect identified
Areas of acellular tumor osteoid, necrotic and/or fibrotic material attributable to the effect of chemotherapy with other areas of histologically viable tumor
Predominant areas of acellular tumor osteoid, necrotic and/or fibrotic material attributable to the effect of chemotherapy with only scattered foci of histologically viable tumor cells identified
No histologic evidence of viable tumor identified within the entire specimen
The histopathology slide below shows osteosarcoma – post neoadjuvant treatment. All tumor cells are wiped out, with only a small amount of matrix and reactive/edematous tissue remaining.
Among tumors of the extremity, distal sites have a more favorable prognosis than proximal sites.
Axial skeleton primary tumors:
- Greatest risk of progression and death
- Pelvic osteosarcomas make up 7% to 9% of all osteosarcomas
- Current overall survival rate is 20% to 47%
Osteosarcoma of craniofacial bones:
- Complete resection of the primary tumor with negative margins is essential for cure.
- High rate of inferior necrosis following neoadjuvant chemotherapy, BUT fewer patients with craniofacial primaries develop systemic metastases than patients with osteosarcoma in the extremities
- ? Related to the relatively smaller size and higher incidence of lower grade tumors in osteosarcoma of the head and neck.
Larger tumors have a worse prognosis than smaller tumors. (Inconsistent in recent literature)
The significance of these factors is usually derived retrospectively and not fully validated:
- Good Prognosis:
- Lack of LOH at RB
- Absence of telomerase activity or activation of alternative lengthening of telomeres
- Poor prognosis:
- Her-2 over expression (variable consistency in literature)
- Ezrin expression (membrane cytoskeleton linkage protein)
- VEGR expression