Oesophageal Carcinoma cNode Status Predicts OS Benefit Of Neoadjuvant Chemoradiation

Clinical nodal status could guide neoadjuvant chemoradiation decision-making for oesophageal carcinoma

medwireNews: Research suggests that neoadjuvant chemoradiation significantly improves overall survival (OS) in oesophageal adenocarcinoma patients who are clinically node-positive (cN+) but has no such benefit over surgery alone for node-negative (cN–) individuals.

The study reports the outcome of 1309 US patients with cT1b N1–N3 or T2–T4 N0–3 middle or lower oesophageal cancer who were treated between 1998 and 2006. Patients received neoadjuvant chemoradiation before surgery (n=539) or surgery alone (n=770) and were followed up for a median of 73.3 months.

Initial analysis indicated that 3-year OS was significantly higher with neoadjuvant chemoradiation, at 49% versus 38%, say Moshim Kukar, from Roswell Park Cancer Institute in Buffalo, New York, USA, and co-investigators in JAMA Surgery.

Stratifying by cN status demonstrated that OS was significantly improved with receipt of neoadjuvant therapy for cN+ patients, with unadjusted 3-year OS rates of 47% versus 25% without such therapy and a propensity-adjusted hazard ratio (HR) of 0.52.

By contrast, although there was a trend towards better 3-year OS with neoadjuvant chemoradiation for the cN– patients, at 54% versus 45%, this difference did not reach significance. And propensity-adjusted analysis gave a nonsignificant HR of 0.84 indicating neoadjuvant treatment had no impact on OS.

The researchers acknowledge the potential for misclassification or downgrading with neoadjuvant treatment and note the need for image-guided biopsy before treatment to give an accurate nodal status.

Indeed, they admit that clinical and pathological staging were not in agreement in up to a quarter of the patients in the study but report that further analysis of patients whose pathological and clinical node status matched confirmed that neoadjuvant chemoradiation only had a significant impact on OS for those who were truly cN+.

“These conclusions stress the importance for accurate clinical staging with respect to nodal status as this may have implications on treatment algorithms”, the researchers write.

“Methods to accurately diagnos[e] or even predict truly positive nodal disease warrant clinical application and further study.”

Wayne Hofstetter, from the University of Texas MD Anderson Cancer Center in Houston, USA, cautions in an accompanying comment that limitations in clinical staging mean that guiding neoadjuvant chemoradiation use based on nodal status could mean patients are over- or under-treated.

“Using genetic markers will hopefully eliminate this discussion of unnecessary preoperative therapy”, he suggests.

“Predicting patients who are at risk for systemic recurrence and targeting vulnerable areas of the tumor genome/expression will provide more opportunity for cure with lower background toxicity”, he writes.

“Similarly, patients with markers indicating low risk for recurring within or outside of the surgical field, and those who are potentially curable but markers indicate relative resistance to preoperative therapy, would go straight to resection.”

References

Gabriel E, Attwood K, Du W, et al. Association between clinically staged node-negative esophageal adenocarcinoma and overall survival benefit from neoadjuvant chemoradiation. JAMA Surg 2015; Advance online publication 11 November.doi:10.1001/jamasurg.2015.4068

Hofstetter WL. Preoperative chemoradiation in an era of suboptimal clinical staging. JAMA Surg 2015; Advance online publication 11 November.doi:10.1001/jamasurg.2015.4047.

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