The independent adverse prognostic factors for distant recurrence and disease specific survival differ from those identified for subsequent local recurrence. Patients with microscopically positive surgical margins or patients who present with locally recurrent disease are at increased risk for subsequent local recurrence and tumor-related mortality. Specific histopathologic subtypes are associated with increased risks for local failure and tumor-related mortality.

The TMPRSS2-ERG fusion, present in 50% of prostate cancers, is less common in prostatic intra-epithelial neoplasia (PIN), raising questions about whether TMPRSS2-ERG contributes to disease initiation. We identified the translational start site of a common TMPRSS2-ERG fusion and showed that transgenic TMPRSS2-ERG mice develop PIN, but only in the context of PI3-kinase pathway activation. TMPRSS2-ERG positive human tumors are also enriched for PTEN loss, suggesting cooperation in prostate tumorigenesis.

ObjectiveTo define the significance of positive microscopic resection margins in a large cohort treated for soft tissue sarcoma. MethodsThe authors analyzed 2,084 patients with localized primary soft tissue sarcoma (all anatomic sites) treated from 1982 to 2000. Clinicopathologic variables studied included tumor site, size, depth, histologic type, grade, and resection margin status. Treatment other than resection was not analyzed. Study endpoints included local and distant recurrence-free and diseasespecific survival rates, estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed using the log-rank test and the Cox proportional hazards model. ResultsMedian follow-up was 50 months. After primary resection, 1,624 (78%) patients had negative and 460 (22%) had positive resection margins. Having positive margins nearly doubled the risk of local recurrence and increased the risk of distant recurrence and disease-related death. Seventy-two percent of patients with positive margins had no recurrence. Resection margin did not predict local control for retroperitoneal sarcomas or fibrosarcomas. Resection margin remained significantly associated with distant recurrence-free survival and disease-specific survival across all subsets after adjusting for other prognostic variables. The overall 5-year disease-specific survival rates for negative and positive margins were 83% and 75%. ConclusionsPositive microscopic resection margins significantly decrease the local recurrence-free survival rate for other-than-primary fibrosarcoma and retroperitoneal sarcomas, and independently predict distant recurrence-free survival rates and disease-specific survival rates for all patient subsets. Adjuvant therapy should be considered in the management of soft tissue sarcoma to increase local control. Because 72% of positive margins did not equate with inevitable local recurrence, considerable clinical judgment is required in considering additional treatment. Microscopic resection margins should be considered for inclusion in staging systems and treatment algorithms that address local recurrence.

In this study of patients with retroperitoneal STS, stage at presentation, high histologic grade, unresectable primary tumor, and positive gross margin are strongly associated with the tumor mortality rate. Patients approached with curative intent should undergo aggressive attempts at complete surgical resection. Incomplete resection should be undertaken only for symptom relief.

The natural history of primary synovial sarcoma of the extremity is related to tumor size and invasion of bone and neurovascular structures.