Induction Therapy Does Not Improve Survival for Clinical Stage T2N0 Esophageal Cancer

Abstract

Introduction This study compared survival after initial treatment with esophagectomy as primary therapy to induction therapy followed by esophagectomy for patients with clinical T2N0 (cT2N0) esophageal cancer in the National Cancer Database (NCDB). Methods Predictors of therapy selection for patients with cT2N0 esophageal cancer in the NCDB from 1998–2011 were identified with multivariable logistic regression. Survival was evaluated using Kaplan-Meier and Cox proportional-hazards methods. Results Surgery was used in 42.9% (2057/4799) of cT2N0 patients. Of 1599 esophagectomy patients for whom treatment timing was recorded, induction therapy was used in 44.1% (688). Pre-treatment staging was proven accurate in only 26.7% of patients (210/786) who underwent initial surgery without induction treatment and had complete pathologic data available: 41.6% (n=327) were upstaged and 31.7% (n=249) were downstaged. Adjuvant therapy (chemotherapy or radiation therapy) was given to 50.2% of patients treated initially with surgery who were found after resection to have nodal disease. There was no significant difference in long-term survival between strategies of primary surgery and induction therapy followed by surgery (median 41.1 versus 41.9 months, p=.51). In multivariable analysis, induction therapy was not independently associated with risk of death (HR 1.16, p=.32). Conclusions Current clinical staging for early-stage esophageal cancer is highly inaccurate, with only a quarter of surgically resected cT2N0 patients found to have had accurate pre-treatment staging. Induction therapy for patients with cT2N0 esophageal cancer in the NCDB is not associated with improved survival.

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

“…In conclusion, given that stage-migration remains an issue even with the best staging procedures it is plausible thinking about a role of a neo-/adjuvant therapy in cT2N0M0 EC (21). Furthermore we think that on the basis of the current evidence it is probable that neo-adjuvant therapy is effective in some cases.…”

Comparison of neoadjuvant chemotherapy versus upfront surgery with or without chemotherapy for patients with clinical stage III esophageal squamous cell carcinoma

“…3 Additionally, even for advanced esophageal cancer, postoperative survival has not been shown to improve in patients with depth of invasion of T2 or clinical stage II who received NAC. 4,5 Furthermore, most recent studies that have shown a survival benefit of neoadjuvant treatment used patients who received surgery alone as a control group. 1 In the JCOG 9907 study that was designed to compare NAC with adjuvant chemotherapy, NAC showed a statistically significant survival benefit.…”

Western strategy for EGJ carcinoma

“…A further issue to consider is the correct management of clinically staged T2N0 (cT2N0) tumors, which constitute approximately 5-15% of the cases in Western series [36,37]. Considering the limited extent of the disease in these cases, preoperative therapies-burdened by negligible morbidity-could represent overtreatment.…”

“…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?…”

“…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? (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].…”