Discussion
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 sarcoma6,9, 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.9,11,12 We therefore sought to
examine trends in incident lymph node metastasis and lymph node sampling
in a pediatric and young adult cohort.
We conducted a retrospective survival analysis of 1303 pediatric
patients with CCS, epithelioid, and synovial sarcoma in the National
Cancer Database. Our results confirm that children and young adults with
synovial sarcoma have infrequent lymph node metastasis (2.2%), while
nodal involvement is more common in patients with CCS (14.6%) and
epithelioid sarcoma (15.0%). These frequencies are comparable to those
reported in the adult literature6,9 and support that
synovial sarcoma does not have a strong proclivity for lymphatic spread
in children.
By utilizing a national database, our study was able to examine the
associations between lymph node sampling and overall survival for
individual NRSTS histologic subtypes of CCS, epithelioid, and synovial
sarcoma. Previous research on lymph node sampling in pediatric NRSTS has
relied on single center studies8,17,18, cohorts of
adults and children6,19,20, or analyses that group
histologic subtypes.3,5 Given the known heterogeneity
in treatment and outcomes of NRSTS subtypes7,9 as well
as the differences in survival between older adults and pediatric
patients with NRSTS20, our study results add clarity
to the significance of lymph node metastasis in pediatric patients with
CCS, epithelioid, and synovial sarcoma subtypes.
This study supports lymph node metastasis as an independent risk factor
for OS in pediatric patients with CCS, epithelioid, and synovial
sarcoma, but we found tumor histology did not significantly modify this
relationship. This finding contrasts with results from a NCDB study of
adults with NRSTS, which showed the associated impact of lymph node
metastasis on OS was worse in histologic subtypes with good overall
prognoses, such as epithelioid sarcoma11. With the
rarity of lymph node metastasis seen for each histological subtype in
our cohort, it is possible that our study was underpowered to detect
this difference.
Current Children’s Oncology Group (COG) and European Society for Medical
Oncology (ESMO) practice guidelines recommend routine lymph node
sampling for pediatric patients with CCS and epithelioid sarcoma, but
not synovial sarcoma.21,22 We found lymph node
sampling occurred in only half of patients with CCS and epithelioid
sarcoma, and this trend was stable across the 12-year study period. We
speculate that the inconsistent practice of lymph node sampling may be
due to variation in practice patterns. For example, center-specific
variation in routine use of FDG-PET scans or other patient-specific
factors which limit the ability to obtain FDG-PET scans may
differentially drive staging procedures. Improved adherence to lymph
node sampling recommendations may be an important goal for future
quality improvement studies.
Our results show an associated survival benefit to lymph node sampling
in pediatric patients with CCS. We speculate that sampling procedures
more accurately identified lymph node metastases in patients with CSS,
leading to augmented treatment plans and ultimately improved patient
survival. Unfortunately, database constraints prevented us from
detecting if augmented treatment plans were in fact implemented for
these patients. However, in support of this theory, we found that
children with CCS who did not undergo lymph node sampling had inferior
survival rates, which were similar to the 2-year OS seen in those with
lymph node metastasis. Given the higher incidence of lymph node
metastasis in CCS as seen in this study, our findings support the
recommendation for routine lymph node sampling in this histologic
subtype.
Our findings also support the recommendation to avoid routine lymph node
sampling in patients with synovial sarcoma without clinical or
radiographic concern for nodal involvement. As previously mentioned, our
study found that lymph node metastasis was rare in children and young
adults with synovial sarcoma. Additionally, children with synovial
sarcoma who underwent lymph node sampling had an associated decreased
survival, likely because those for whom sampling procedures were
recommended were at higher risk for advanced disease. Conversely,
patients with synovial sarcoma who had negative lymph nodes had similar
2-year OS to those who did not undergo a lymph node sampling procedure.
The benefits of lymph node sampling for epithelioid sarcoma in children
remains unclear. Our results showed that confirming lymph node
involvement by sampling was not significantly associated with improved
OS, and 2-year OS for patients with epithelioid sarcoma were similar
between those who had negative nodes and those who did not undergo a
sampling procedure. However, our study corroborates that epithelioid
sarcoma does have a high propensity for lymph node involvement.
Locoregional staging may remain important for treatment planning for
patients with epithelioid sarcoma, as previous literature suggests that
imaging underestimates nodal involvement in soft tissue
sarcomas.23
We acknowledge there were several limitations to our study. First, we
utilized a retrospective database with limited granularity. For example,
we could not accurately analyze disease-free survival or distinguish
timing or technique for lymph node sampling. Second, our inclusion
criteria restricted the study cohort to patients who underwent primary
surgical resection or primary site radiation. Therefore, our study
results may not extrapolate to patients with unresectable or advanced
metastatic disease. Finally, there may exist differential sampling bias
in our results: in patients with no clinical suspicion for nodal
involvement, it is probable that physicians were more likely to sample
lymph nodes in those with CCS or epithelioid sarcoma as compared to
synovial sarcoma because of current COG and ESMO practice guidelines.
Despite these limitations, our results suggest that pediatric patients
with CCS and epithelioid sarcoma, but not synovial sarcoma, are at
substantial risk of lymph node metastasis. Lymph node sampling was
associated with improved survival in patients with CCS, yet it was
inconsistently performed in patients with this subtype. Additionally,
the impact of lymph node sampling in patients with epithelioid sarcoma
remains unclear. Future research could focus on determining the
significance of lymph node sampling in pediatric patients with
epithelioid sarcoma, as lymph node metastasis is common in this subtype.
Conflict of Interest Statement: The authors have no potential
conflicts of interest.
Acknowledgments: None