Neoadjuvant Chemoradiotherapy Survival Benefit In Oesophageal Cancer Questioned

Patients with stage II or III oesophageal adenocarcinoma do not benefit from the addition of radiotherapy to chemotherapy in the neoadjuvant setting

medwireNews: Research suggests that neoadjuvant chemoradiotherapy does not confer a survival advantage over neoadjuvant chemotherapy in patients with locally advanced oesophageal adenocarcinoma.

The research team conducted a propensity-score matched analysis to account for confounders including age of 70 years or more, male gender, American Society of Anesthesiologists grade, clinical tumour stage and nodal status.

Overall and disease-free survival (OS, DFS) at 3 years were 57.9% and 52.9%, respectively, for 221 patients with stage II or III adenocarcinoma of the oesophagus or gastro-oesophageal junction who received neoadjuvant chemotherapy plus radiotherapy. These did not differ significantly from the corresponding 53.4% and 48.9% rates observed in their 221 counterparts given chemotherapy alone.

The results were similar in a COX regression analysis that additionally adjusted for age and year of surgery as continuous variables, and included the total study cohort of 301 chemoradiotherapy- and 307 chemotherapy-treated patients drawn from 10 European surgical databases.

The lack of a significant survival advantage with chemoradiotherapy was despite significant improvements in pathological endpoints. Specifically, patients in the chemoradiotherapy group were significantly more likely to be down-staged post-surgery relative to those given chemotherapy, with ypT0 and ypN0 incidence rates of 26.7% versus 5.0% and 63.3% versus 32.1%, respectively, in the matched population.

Chemoradiotherapy was also associated with a significantly reduced rate of R1 or R2 resection margins, at 7.7%, compared with 21.8% for the chemotherapy group.

Lead author George Hanna, from Imperial College London in the UK, and team note that there was a significantly increased risk of anastomotic leak with chemoradiotherapy (23.1 vs 6.8%), but in-hospital mortality and other major postoperative morbidity were comparable.

Altogether the findings indicate that survival differences between neoadjuvant chemoradiotherapy and chemotherapy “may be relatively modest, if present at all, and suggest that a large sample size is required for prospective [randomised controlled trials] that compare these modalities”, they say.

The team emphasizes in the Annals of Oncology that “this retrospective study does not provide a definitive answer to the unsolved question of the comparative benefits on [neoadjuvant chemotherapy plus surgery] and [neoadjuvant chemoradiotherapy plus surgery] in esophageal adenocarcinoma but supports the importance of the ongoing NeoAEGIS trial and its surgical quality measures.”

Reference

Markar SR, Noordman BJ, Mackenzie H, et al. Multimodality treatment for esophageal adenocaricnoma: multi-center propensity-score matched study. Ann Oncol; Advance online publication 25 October 2016. doi:10.1093/annonc/mdw560

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