New perspectives for staging and prognosis in soft tissue sarcoma

Background: Data suggest that the current American Joint Committee on Cancer (AJCC) soft tissue sarcoma (STS) staging criteria merit further evaluation. We sought to identify and validate factors as enhanced descriptors of STS clinical behavior. Methods: Prospectively accrued data were analyzed for 1,091 AJCC stage I to III primary STS patients who had complete macroscopic resection at our institution from 1996 to 2007. Study factors were examined by univariable and multivariable analyses to identify independent prognostic factors for disease related mortality and overall survival (OS). Results: In contrast to the current AJCC STS staging system, which stratifies size into T1 (≤5 cm) and T2 (>5 cm) groups, we demonstrated three distinct cohorts (P < 0.0001): T1 (≤5 cm; 5-year OS 85%), T2 (5 to 15 cm; OS 68%), and T3 (>15 cm; OS 52%). A two-category system of histologic grade was demonstrably as informative as the current four histologic grade AJCC system. A multivariable Cox proportional hazard model identified tumor size (5 to 15 cm vs. ≤5 cm, P = 0.03; or >15 cm vs. ≤5 cm; P < 0.0001), nonextremity primary site (P = 0.0016), disease of high histologic grade (P = 0.001), specific histology (P = 0.001), and margin positivity (P < 0.0001) as statistically significant adverse independent prognostic factors. Recurrence during follow-up was the most significant risk factor for STS-specific mortality (P < 0.0001). Conclusion: Tumor size and grade in the AJCC STS staging system need revision; moreover, primary site, histologic subtype, margin status, and recurrence offer additional relevant prognostic insight. Incorporation of these factors may enhance the AJCC staging system, thereby further facilitating individualized therapeutic strategies for STS patients.