Predictors of Lymph Node Involvement by Soft Tissue Sarcoma of the Trunk and Extremity: An Analysis of the National Cancer Database

Abstract

Background and ObjectivesLymph node metastases (LNM) in soft tissue sarcoma (STS) of the trunk and extremity are rare but are associated with worse survival. Established risk factors for LNM in this group are based on small institutional retrospective reviews. This study identifies the risk factors associated with LNM in otherwise non-metastatic trunk/extremity STS patients using the National Cancer Database (NCDB) and sought out to delineate a high-risk group that may be considered for pathologic nodal evaluation.MethodsThe files of 10,731 patients with STS of the trunk/extremity without distant metastasis from 2004 - 2015 were evaluated. Exclusion criteria included neoadjuvant therapy and a lack of pathologic nodal evaluation. Univariate and multivariable logistic regression models were performed to evaluate variables associated with LNM.ResultsOf the total of 10,731 patients, 223 (2.1%) had LNM. On multivariable analysis, LNM was associated with Grade 3 tumors (odds ratio (OR) 15.6, 95% confidence interval (CI) 6.36 - 38.04, p < 0.001) and clear cell/angiosarcoma/rhabdomyosarcoma/epithelioid (CARE) histology (OR 4.72, 95% CI 3.35 - 6.66, p < 0.001), lymphovascular invasion (LVI) (OR 5.86, 95% CI 3.33 - 10.31, p < 0.001, and bone invasion (BI) (OR 2.73, 95% CI 1.32 - 5.61, p = 0.006). Patients with Grade 3 CARE tumors (n = 402) had an 11.9% risk of LNM vs. 1.7% of adults without all these characteristics (p < 0.001). Patients with Grade 3 CARE tumors and either LVI or BI (n = 36) had a 33.3% risk of LNM.ConclusionsHigh-grade and CARE histology are associated with LNM in STS. Adult patients with both features have an overall 11.9% risk of LNM and may be considered for pathologic LN assessment, particularly with the presence of LVI or BI.

Trends of lymph node sampling and metastasis in pediatric patients with clear cell, epithelioid, and synovial sarcomas

“…Lymph node metastases in pediatric patients with NRSTS are associated with a poor prognosis. 3,6,9,11 Adult studies suggest that CCS and epithelioid sarcoma have a higher risk of lymph node metastasis as compared to synovial sarcoma 6,9 , however this association remains unconfirmed in children. Clarifying the incidence and impact of nodal metastasis for these histologic subtypes is important as locoregional control measures for nodal disease can reduce tumor recurrence.…”

“…[3][4][5] One common grouping of NRSTS is by propensity for early lymph node metastasis. Most NRSTS rarely metastasize to lymph nodes 4,6 , but higher risk NRSTS subtypes historically included clear cell sarcoma of soft tissue (CCS), epithelioid sarcoma, and synovial sarcoma. 7 Over the past two decades, large database studies in adults and single-center studies in children have corroborated lymph node metastases are prevalent in up to 30% of patients with CCS and epithelioid sarcoma.…”

“…7 Over the past two decades, large database studies in adults and single-center studies in children have corroborated lymph node metastases are prevalent in up to 30% of patients with CCS and epithelioid sarcoma. 4,6,[8][9][10] Conversely, synovial sarcoma in adults is now understood to have an incidence of lymph node metastasis as low as 4.2% 6,9 , but this association has not been well-studied in children.…”

“…Understanding the incidence of lymph node involvement in children with NRSTS tumors is important, as both the adult and pediatric literature support an association between lymph node metastasis and inferior OS across all NRSTS subtypes. 3,6,9,11 Additionally, patients identified with lymph node metastasis can receive targeted radiation or completion lymphadenectomy to reduce tumor recurrence. 12 However, physicians must weigh suspicion for lymphatic involvement against the risks associated with sampling procedures, including wound infection and lymphedema.…”

Pathologic nodal staging for clinically node negative soft tissue sarcoma of the extremities

“…This possibility has important clinical implications as regional lymphatic spread in STS in the absence of distant metastases has been identified as a factor predicting worse overall survival 4,6,10,12,13 . A prior study examining factors associated with nodal positivity in this database included clinically node positive patients, which may be distinct from microscopically positive disease in clinically node negative patients, and combined the CARE histologies into one group, which did not allow for a discrete examination of the diverse biology under the STS umbrella 14 . Therefore, regional lymph node evaluation to identify clinically occult disease may be important for prognosis and subsequent management for certain subtypes at high risk of regional lymphatic spread.…”