Prognostic value of pathological lymph node status and primary tumour regression grading following neoadjuvant chemotherapy - results from the MRC OE02 oesophageal cancer trial

Abstract

Aims: Neoadjuvant chemotherapy (NAC) remains an important therapeutic option for advanced oesophageal cancer (OC). Pathological tumour regression grade (TRG) may offer additional information by directing adjuvant treatment and/or follow-up but its clinical value remains unclear. We analysed the prognostic value of TRG and associated pathological factors in OC patients enrolled in the Medical Research Council (MRC) OE02 trial.

Methods and results: Histopathology was reviewed in 497 resections from OE02 trial participants randomised to surgery (S group; n = 244) or NAC followed by surgery [chemotherapy plus surgery (CS) group; n = 253]. The association between TRG groups [responders (TRG1-3) versus non-responders (TRG4-5)], pathological lymph node (LN) status and overall survival (OS) was analysed. One hundred and ninety-five of 253 (77%) CS patients were classified as 'non-responders', with a significantly higher mortality risk compared to responders [hazard ratio (HR) = 1.53, 95% confidence interval (CI) = 1.05-2.24, P = 0.026]. OS was significantly better in patients without LN metastases irrespective of TRG [non-responders HR = 1.87, 95% CI = 1.33-2.63, P < 0.001 versus responders HR = 2.21, 95% CI = 1.11-4.10, P = 0.024]. In multivariate analyses, LN status was the only independent factor predictive of OS in CS patients (HR = 1.93, 95% CI = 1.42-2.62, P < 0.001). Exploratory subgroup analyses excluding radiotherapy-exposed patients (n = 48) showed similar prognostic outcomes.

Conclusion: Lymph node status post-NAC is the most important prognostic factor in patients with resectable oesophageal cancer, irrespective of TRG. Potential clinical implications, e.g. adjuvant treatment or intensified follow-up, reinforce the importance of LN dissection for staging and prognostication.

Keywords: neoadjuvant chemotherapy; oesophageal carcinoma; tumour regression grade.

Figure 1

Study profile, Consolidated Standards of Reporting Trials (CONSORT).

Figure 2

Overall survival stratified by tumour regression grade (TRG) in patients treated by neoadjuvant therapy or surgery alone. Survival of patients with TRG1, 2 or 3 tumours was similar, and markedly different from patients with TRG4 or 5 tumours. Survival of patients treated with surgery alone was similar to that of patients treated with chemotherapy plus surgery with TRG4 or 5 tumours.

Figure 3

Five‐year overall survival stratified by combined tumour regression grade (TRG) in patients treated with neoadjuvant chemotherapy plus surgery in the OE02 trial. Patients with TRG1–3 tumours (responders) survived significantly longer than patients with TRG4–5 tumours (non‐responders) [hazard ratio (HR) = 1.53, 95% confidence interval (CI) = 1.05–2.24, P = 0.026].

Figure 4

Five‐year overall survival stratified by combined tumour regression grade (TRG) and lymph node status in patients treated with neoadjuvant chemotherapy plus surgery. Responders (TRG1–3 tumours) without lymph node metastasis (node negative) survived significantly longer than responders with lymph node metastasis (node positive) [hazard ratio (HR) = 2.21, 95% confidence interval (CI) = 1.11–4.10, P = 0.024]. Non‐responders (TRG4–5 tumours) without lymph node metastasis (node negative) survived significantly longer than non‐responders with lymph node metastasis (node positive) (HR = 1.87, 95% CI = 1.33–2.63, P < 0.001). [Colour figure can be viewed at http://wileyonlinelibrary.com]