Validation of tumour-negative lymph node size as a novel independent prognostic biomarker in oesophagogastric adenocarcinoma: post hoc analysis of the UK MRC OE05 and ST03 randomised trials
In brief
Large tumor-negative lymph nodes cut death risk by about 20% in esophagogastric cancer
In a pooled analysis of 1,367 patients from two phase III trials, those whose resected specimens contained a tumor-negative lymph node larger than 10 mm lived longer, with roughly a 20% lower risk of death and progression. The finding held after adjusting for other factors, suggesting LN size could help refine prognosis, though the biological basis remains unclear.
- Journal
- ESMO open (Q1)
- Published
- 12 August 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- E Budginaite, M Kloft, D R Magee, S Jolani, T Goetze, M G Nankivell, et al.
- PMID
- 42585971
- DOI
- 10.1016/j.esmoop.2026.108348
Why clinicians should know about it
- Picked for Surgical Oncology (top studies of the week, 11 October 2026): LN‑negative size prognostic biomarker after resection of OG adenocarcinoma
- Picked for Surgery (top studies of the week, 11 October 2026): LN‑negative size independently predicts OS in OG adenocarcinoma
Abstract
BACKGROUND: The size of tumour-negative regional lymph nodes (LNnegs) may be associated with the host antitumour immune response in patients with oesophagogastric adenocarcinoma (OGAC). In the OE02 trial, larger LNnegs were independently associated with improved overall survival (OS); however, the prognostic relevance of LNneg size has not been validated in an independent OGAC population. PATIENTS AND METHODS: Resection specimens from 1367 patients from two phase III trials (OE05, n = 652; ST03, n = 715) were analysed. The largest LNneg per patient was identified on digitised slides stained with haematoxylin-eosin using an automated segmentation pipeline. Lymph node ratio [LNratio; number of metastatic lymph nodes (LNs) divided by the total number of resected LNs] was calculated for patients with stage ypN1+ cancer. Anthracotic pigment burden was quantified using a deep learning model. Associations among LNneg size, primary tumour location, recurrence, and survival were evaluated. RESULTS: LNneg size and pigment burden differed by primary tumour location. LNnegs from oesophageal/junctional cancers were larger and had greater pigment burden than those from gastric cancers (all P < 0.0001). Larger LNnegs were associated with a lower recurrence rate (P = 0.033) and lower LNratio (P < 0.0001). Patients with LNnegs with a long axis diameter >10 mm had improved OS [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.70-0.93, P = 0.0147) and progression-free survival (HR 0.80, 95% CI 0.70-0.92, P = 0.0092). Presence of large LNnegs was independently prognostic after multivariable adjustment. CONCLUSIONS: This study validates LNneg size as a novel independent prognostic biomarker in patients with locally advanced OGAC treated with cytotoxic chemotherapy and surgery. Variation in LNneg size and pigment burden by primary tumour location may suggest anatomical or microenvironmental differences in LNneg biology that may affect LN assessment and immune-related characteristics. Further studies integrating quantitative microarchitectural and immune profiling of LNnegs are warranted to clarify the mechanisms driving LNneg enlargement and the potential functional relevance of pigment deposition.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.