What is the most prognostic factor for Esophageal (oesophageal) cancer?

Lymph Node Status is the Most Prognostic Factor for Oesophageal Cancer

Lymph node involvement is the single most important prognostic factor in oesophageal cancer, significantly outweighing both depth of invasion and vascular invasion in determining patient outcomes. 1

Evidence for Lymph Node Status as Primary Prognostic Factor

• The 2011 systematic review in the European Journal of Surgical Oncology definitively established lymph node involvement as the single most important prognostic factor in oesophageal cancer 1
• Multivariate analysis demonstrated lymph node status to be the only significant independent prognostic factor in submucosal oesophageal cancer 2
• The 2018 MRC OE02 trial confirmed that lymph node status post-neoadjuvant chemotherapy is the most important prognostic factor in patients with resectable oesophageal cancer, irrespective of tumor regression grade 3
• Long-term survival rarely exceeds 25% in patients with lymph node involvement, even with complete tumor resection 4

Comparison with Other Prognostic Factors

Depth of Invasion (T stage)

• While depth of invasion is important, its prognostic value is primarily through its correlation with lymph node metastasis 2
• Subdivisions of tumor depth did not reach significance as independent prognostic factors in multivariate analysis 2
• However, submucosal invasion >500μm does significantly worsen prognosis in early-stage disease 4

Vascular Invasion

• Vascular invasion is an independent prognostic variable specifically in cardial and distal tumours 5
• However, its overall prognostic impact is less significant than lymph node status across all oesophageal cancer types 5, 1
• Lymphatic invasion correlates with prognosis in univariate analysis but not in multivariate analysis when lymph node status is included 2

Quantitative Aspects of Lymph Node Involvement

• The 7th edition of the TNM Classification stratified lymph node involvement according to the number of lymph nodes involved, recognizing its critical prognostic importance 1
• The number of metastatic lymph nodes independently predicts both overall survival and relapse-free survival 6
• The lymph node ratio (metastatic LNs/removed LNs) closely correlates with survival 6
• Extracapsular lymph node involvement is an independent negative prognostic factor, occurring more frequently in adenocarcinoma (66%) than squamous cell carcinoma (35%) 7

Clinical Implications

• Accurate assessment of lymph node status is essential for treatment planning and prognostication 2
• The assessment of lymph nodes should include a full dissection of the specimen to define the total lymph node number removed and the total involved by tumour 5
• Imaging to determine the extent of lymph node involvement often requires a combination of modalities to avoid under-staging 1
• A combination of imaging methods such as endoscopic ultrasound-guided fine-needle aspiration, computed tomography, and positron emission tomography is necessary for accurate diagnosis of lymph node metastasis 2

Surgeon and Hospital Factors

• The annual number of oesophagectomies per surgeon is an important prognostic factor for both short-term and long-term survival 5, 4
• Procedures performed at high-volume centers have better outcomes 4
• The extent of lymphadenectomy remains controversial, with some studies indicating better overall prognosis with more extensive lymphadenectomy, while others show no survival benefit from removing more nodes, especially in patients having received neoadjuvant oncological therapy 5

In conclusion, when evaluating the most prognostic factor for oesophageal cancer among lymph node status, depth of invasion, and vascular invasion, the evidence clearly establishes lymph node involvement as the most significant determinant of patient outcomes.