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

Abstract

Background While 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 (OS). Methods cT2N0 esophageal cancer patients receiving induction therapy or upfront esophagectomy (UE) were identified in the National Cancer Data Base (NCDB). UE patients were dichotomized as 1) pathologically upstaged or 2) same-or down-staged. Logistic regression models identified variables associated with upstaging and Kaplan-Meier analysis compared median OS. Results From 2006–2012, 932 (52.2%) cT2N0 patients received UE, while 853 (47.8%) received induction therapy first. 326/713 (45.7%) UE patients were upstaged. 87/326 (26.7%) patients had T upstaging, 98/326 (30.1%) had N upstaging, and 141/326 (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 (LVI, 57.1% versus 17.7%), both p<0.001. Variables associated with upstaging included LVI (OR 6.0, 95% CI 2.9 – 12.5, p<0.001) and tumor grade 3 (OR 9.4, 1.8 – 48.4, p=0.007). Of upstaged UE patients, only 144 (44.2%) received adjuvant therapy. The median OS 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). Conclusions Half of all cT2N0 patients were pathologically upstaged after UE with worse survival compared to 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.

Cancer of the esophagus and esophagogastric junction: an 8th edition staging primer

“…Due to limitations with modern staging with endoscopic ultrasound (EUS) and computed tomography-positron emission tomography (CT-PET) patients with cT2N0 disease are under staged in approximately half of cases and over staged in about one quarter of tumours in this group (10,11). Although included in many trials of neoadjuvant treatment, whether neoadjuvant treatment brings benefit to patients with this clinical stage is questionable (12)(13)(14).…”

Should cT2N0M0 be managed as a localized or locally advanced esophageal carcinoma?

“…If on one hand respective surgery was always considered the first choice for the localized clinical stages on the other hand it should be taken in mind that the clinical stage could not correspond with the same pathologic stage after upfront surgery. This is particularly true for the cT2N0M0 (10). Of course the risk of clinical understaging is directly correlated with the type of the staging work-up.…”

“…For patients' candidate to esophagectomy it is now recommended that the staging should include a neck-ChestAbdomen CT-scan, an endoscopic ultrasound (EUS) and an FDG-PET/CT (11). However, it has been described that even with a staging including EUS and FDG-PET/CT, cN0 became pN+ after an upfront esophagectomy in 39% to 55% of cT2N0 patients (10,12,13).…”

Western strategy for EGJ carcinoma

“…(40-50% of such cases are upstaged in upfront surgery) [36][37][38], and those cases could therefore benefit from neoadjuvant treatments [38]. For this reason, parameters such as tumor grade and lymphovascular invasion should be taken into account along with clinical staging when attempting to predict nodal invasion and to identify potentially understaged patients before choosing the treatment plan [38].…”

“…Despite these considerations, there has been a tendency in more recent years to treat a greater number of cT2N0 patients with multimodal neoadjuvant approaches [35], given that it reportedly yields better biological control of the disease (6-18% of cT2N0 patients treated with multimodal therapy were pathologic complete responders) and a higher rate of radical resection [36][37][38]. However, any observed advantage in terms of overall and disease-free survival comes from comparing multimodality therapy with surgery alone in this clinical setting [36][37][38]. It should be noted that these results cannot be considered to be conclusive, especially because a nonnegligible percentage of clinical N0 cases are actually pathological N?…”