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Biological and comorbidity factors outweigh lymph node metrics in predicting outcomes after small-bowel
Krishna Kotecha1, Siddharth Darbhamulla2, David L Chan3
1Department of Upper Gastrointestinal Surgery, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia; Northern Clinical School, Faculty of Medicine & Health, University of Sydney, Sydney, Australia.
Background:
Small-bowel neuroendocrine tumours (SBNETs) frequently involve mesenteric lymph nodes. While guidelines suggest minimum lymph node yields (LNY), the independent prognostic relevance of LNY and lymph node ratio (LNR) regarding recurrence remains uncertain in contemporary cohorts.
Methods:
A retrospective analysis of 102 patients undergoing R0/R1 resection for SBNETs (2005-2023) at a single tertiary institution was conducted. The primary outcome was overall survival (OS), and time to recurrence (TTR) was analyzed as a secondary endpoint, with the caveat that recurrence detection is sensitive to surveillance frequency and patient presentation. Literature-informed thresholds (LNY >8, LNR ≤0.46) were applied and validated using exploratory cut-point analysis. Predictors of outcome were assessed using Kaplan-Meier survival analysis and multivariable Cox and logistic regression models.
Results:
At a median follow-up of 8.1 years, the 5-year overall survival (OS) for the entire cohort was 86.0%. On multivariable analysis, older age (HR 1.39; p = 0.037) and higher Charlson Comorbidity Index (HR 1.17; p = 0.093) were the primary drivers of mortality. In contrast, surgical nodal metrics (LNY and LNR) were not independent predictors of OS. Secondary analysis showed that in the localized subgroup (stage I-III), the median TTR was not reached, and the 5-year TTR rate was 73.7%. Independent predictors of recurrence/progression were higher Charlson Comorbidity Index (OR 1.90 per point; p < 0.001), younger age (OR 0.93 per year; p < 0.001), and higher Ki-67 index (OR 1.36 per %; p = 0.011).
Conclusions:
In this cohort, adequate lymphadenectomy (>8 nodes) assisted staging. However, nodal metrics were not statistically significant predictors of recurrence or survival after multivariable adjustment, reflecting the dominant influence of tumor biology (Ki-67) and patient comorbidity (as reflected by the CCI score) on overall survival. Prognostication and surveillance strategies should prioritize biological markers and patient factors over surgical nodal metrics alone.
