Is increased symptom interval associated with advanced stage and poorer outcome? A prospective multicenter study of 220 patients with osteosarcoma around the knee.

Objective: Osteosarcoma is rare disease and there is a strong controversy about the potential impact of symptom interval on the stage of disease and patients' outcomes. We want to assess whether increased symptom interval (SI) is associated with advanced tumor stage and poor prognosis for patients with osteosarcoma.

Methods: We analyzed prospectively collected data of 220 patients younger than 40 years who had osteosarcoma around the knee. Symptom interval was analyzed to evaluate its impact on metastases at diagnosis, tumor volume, chemotherapy response and overall survival.

Results: The median of SI was 64.5 (Q1-Q3: 42-88) days. The 5-year overall survival rate for patients with different length of symptom interval (<42 days, 42-64 days, 65-87 days, > = 88 days) were 0.78 (95 %CI: 0.67-0.89), 0.49 (95 %CI: 0.35-0.63), 0.52 (95 %CI:0.39-0.65), and 0.65 (95 %CI:0.53-0.77) respectively(p = 0.013). Nonparametric test showed increased SI was associated with metastases at diagnosis (p = 0.008), but not associated with large tumor volume or poor chemotherapy response. Cox regression mode test showed that patient with increased SI had higher hazard ratio (42-64 days HR: 2.586 (95 %CI:1.360-4.915); 65-87 days, HR: 2.225 (95 %CI:1.170-4.233)) for poor outcomes compared to short SI (<42 days), though it was not significant in multivariate analysis (p = 0.182).

Conclusion: Increased SI but not the longest SI is associated with higher incidence of metastases at diagnosis; patients can benefit from an earlier diagnosis in terms of survival.