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Clinical T2N0 Esophageal Cancer: Identifying Pretreatment Characteristics Associated With Pathologic Upstaging and the Potential Role for Induction Therapy

Samson P, Puri V, Robinson C, Lockhart C, Carpenter D, Broderick S, Kreisel D, Krupnick AS, Patterson GA, Meyers B, Crabtree T

Ann Thorac Surg. 2016 Apr 12. [Epub ahead of print]

Editorial comment from Professor David Cunningham:
The implications of understaging are also highlighted in a manuscript by Samson et al. in Annals of Thoracic Surgery. The authors reviewed the cases of 932 clinically stage T2N0 patients who received upfront surgery, and 853 clinical T2N0 patients who received induction therapy prior to surgery. Almost half (45.7%) of patients who underwent upfront surgery were upstaged at surgery, of these 44.2% received adjuvant chemotherapy. For patients upstaged at upfront resection median overall survival was worse than for patients who received neoadjuvant chemotherapy (43.9 months versus 27.5 months, p < 0.001), however this difference was mitigated in patients who received adjuvant chemotherapy following upfront surgery (43.8 months versus 34.6 months, p = 0.14). However, as approximately half of patients do not have a performance status sufficient to allow safe delivery of adjuvant therapy following oesophagogastrectomy, neoadjuvant treatment is likely to be helpful for a greater number of patients.



Although studies have suggested standard therapy for clinical T2N0 esophageal cancer should be primary surgery, we hypothesize there is a subgroup for whom induction therapy may result in improved overall survival.


Patients with cT2N0 esophageal cancer receiving induction therapy or upfront esophagectomy (UE) were identified in the National Cancer Data Base. The UE patients were dichotomized as (1) pathologically upstaged, or (2) same-staged or downstaged. Logistic regression models identified variables associated with upstaging, and Kaplan-Meier analysis compared median overall survival.


From 2006 to 2012, 932 cT2N0 patients (52.2%) received UE, and 853 (47.8%) received induction therapy first. In all, 326 of 713 UE patients (45.7%) were upstaged: 87 of 326 (26.7%) had T upstaging; 98 of 326 (30.1%) had N upstaging; and 141 of 326 (43.3%) had both. Patients upstaged after UE had a higher tumor grade (35.1% versus 57.1% grade 3), and a higher rate of lymphovascular invasion (57.1% versus 17.7%; both p < 0.001). Variables associated with upstaging included lymphovascular invasion (odds ratio 6.0, 95% confidence interval: 2.9 to 12.5, p < 0.001) and tumor grade 3 (odds ratio 9.4, 95% confidence interval: 1.8 to 48.4, p = 0.007). Of upstaged UE patients, only 144 (44.2%) received adjuvant therapy. The median overall survival for cT2N0 patients upstaged after UE was 27.5 ± 2.5 months versus 43.9 ± 2.9 months for induction therapy patients (any resultant pathologic stage, p < 0.001).


Half of all cT2N0 patients were pathologically upstaged after UE, with worse survival compared with patients receiving induction therapy. Refining an upstaging model would help select patients for induction therapy and increase the rate of chemotherapy in patients at risk for systemic disease.

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