Abstract
AimsNeoadjuvant 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 resultsHistopathology 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.ConclusionLymph 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.
Highlights
Multimodal therapy is the standard of care for many gastrointestinal malignancies.[1]
E.g. adjuvant treat- importance of lymph node (LN) dissection for staging and ment or intensified follow-up, reinforce the prognostication
For patients with oesophageal carcinoma (OC), surgery preceded by neoadjuvant chemotherapy (NAC) or chemoradiotherapy (NACR) has proven clinical benefit, as reported in the OE02 [Medical Research Council (MRC) oesophageal working group] and CROSS trials, respectively.[2,3]
Summary
Multimodal therapy is the standard of care for many gastrointestinal malignancies.[1] For patients with oesophageal carcinoma (OC), surgery preceded by neoadjuvant chemotherapy (NAC) or chemoradiotherapy (NACR) has proven clinical benefit, as reported in the OE02 [Medical Research Council (MRC) oesophageal working group] and CROSS (chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer) trials, respectively.[2,3] While geographical variation persists in the modality of choice[4,5] and modest differential modality benefits are reported,[6] NAC/NACR results in tumour down-staging, increased rate of complete surgical resection and delayed recurrent and metastatic disease.[7] To date, no randomised controlled trial (RCT) has directly compared neoadjuvant chemotherapy and neoadjuvant chemoradiation. Irrespective of neoadjuvant treatment type, the prognosis of OC patients remains poor, with a 5-year survival of approximately 15%.8,9. It has been suggested that adjuvant chemotherapy or targeted therapies may be beneficial to OC patients with high-risk disease.[8,10] Irrespective of neoadjuvant treatment type, the prognosis of OC patients remains poor, with a 5-year survival of approximately 15%.8,9 it has been suggested that adjuvant chemotherapy or targeted therapies may be beneficial to OC patients with high-risk disease.[8,10]
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