Defining the incidence and clinical significance of lymph node metastasis in soft tissue sarcoma

Abstract

Introduction

The incidence and clinical significance of lymph node metastasis (LNM, N1) in soft tissue sarcoma (STS) is unclear. Recent studies have focused on extremity/trunk STS (ETSTS). We sought to define the subgroup of patients with LNM at sarcoma diagnosis across all disease sites and histologies.

Methods

We identified and categorized 89,870 STS patients from the National Cancer Data Base (1998–2012) by nodal stage. Pathologically confirmed LNM (pN1) were identified in 1404 patients; 1750 had clinically suspicious but not pathologically confirmed LNM (cN1). Survival analyses were performed by Kaplan-Meier method.

Results

Of 3154 patients (3.5%) with pN1 or cN1 LNM at presentation, 1310 had synchronous distant metastasis (M1). LNM affected a small proportion of patients (5.8% head/neck, 5.3% intrathoracic, 5.1% intra-abdominal, 2.0% ETSTS). Angiosarcoma (6%), epithelioid (13%), clear cell (16%), and small cell sarcoma (19%) had the highest incidence of LNM, although liposarcoma, fibrous histiocytoma, and leiomyosarcoma accounted for the greatest number of LNM patients. For pN1M0 disease, median overall survival (OS) was 28.2 months, varying by histology. Among patients with pN1M0 STS, angiosarcoma, clear cell sarcoma, leiomyosarcoma, and fibrous histiocytoma were associated with worse median OS (19.4, 23.8, 27.1, and 29.3 months) compared to epithelioid sarcoma and liposarcoma (49.6 and 56.0 months, p < 0.001).

Conclusion

Despite clinical suspicion, pathologic LN evaluation in STS is inconsistently performed. LNM occurs across anatomic disease sites and is unevenly distributed across histologies. Although M1 disease portends poor prognosis regardless of LN status, LNM predicts worse OS in a histology-dependent manner in M0 disease.

Introduction

Lymph node (LN) metastases (N1) in patients with soft tissue sarcomas (STS) are uncommon, although the true incidence at the time of diagnosis across histologic subtypes and disease location is unclear. The reported incidence of LN metastasis in the literature varies widely, with rates typically reported in the range of 1.6–12% [1], [2], [3], [4], [5], [6], [7], [8]. LN metastasis in STS is a negative prognostic factor for disease-specific survival (DSS) and overall survival (OS) with prior studies reporting 5-year survival rates ranging 10–33% [3], [4], [6], [9], [10] among patients with N1 disease. However, whether the clinical impact of N1 disease approximates that of distant metastatic disease (M1) is unknown as many prior studies examining LN metastasis in STS were often small single institution retrospective series and included patients with N1 disease at both initial disease presentation and at recurrence, those who underwent a variety of multimodality systemic and loco-regional treatments (including chemotherapy, regional therapy, radiation therapy, and lymphadenectomy), and also patients with synchronous M1 disease [3], [7], [8], [9], [10].

The limited literature examining the incidence and clinical implication of LN metastasis in STS has predominantly focused on STS of the trunk and extremity disease sites [8], [9], [11], [12] and a subset of histologic subtypes, including synovial sarcoma, rhabdomyosarcoma, clear cell sarcoma, epithelioid sarcoma, and angiosarcoma [2], [3], [4], [5], [6], [7], [13], [14]. Although it has been thought that patients with these tumors are at the highest risk of LN metastasis, the data are sparse and not without major limitations. The aim of this study was to define the subgroup of STS patients with LN metastasis at diagnosis across all disease sites and histologies using a large prospectively maintained, hospital-based national cancer registry, the National Cancer Database (NCDB).