title: Tumor stage after neoadjuvant chemotherapy determines survival after surgery for adenocarcinoma of the esophagus and esophagogastric junction.
abstract: OBJECTIVE
  Neoadjuvant chemotherapy is established in the management of most resectable esophageal and esophagogastric junction adenocarcinomas. However, assessing the downstaging effects of chemotherapy and predicting response to treatment remain challenging, and the relative importance of tumor stage before and after chemotherapy is debatable.
  
  
  METHODS
  We analyzed consecutive resections for esophageal or esophagogastric junction adenocarcinomas performed at two high-volume cancer centers in London between 2000 and 2010. After standard investigations and multidisciplinary team consensus, all patients were allocated a clinical tumor stage before treatment, which was compared with pathologic stage after surgical resection. Survival analysis was conducted using Kaplan-Meier analysis and Cox regression analysis.
  
  
  RESULTS
  Among 584 included patients, 400 patients (68%) received neoadjuvant chemotherapy. Patients with downstaged tumors after neoadjuvant chemotherapy experienced improved survival compared with patients without response (P < .001), and such downstaging (hazard ratio, 0.43; 95% CI, 0.31 to 0.59) was the strongest independent predictor of survival after adjusting for patient age, tumor grade, clinical tumor stage, lymphovascular invasion, resection margin status, and surgical resection type. Patients downstaged by chemotherapy, compared with patients with no response, experienced lower rates of local recurrence (6% v. 13%, respectively; P = .030) and systemic recurrence (19% v. 29%, respectively; P = .027) and improved Mandard tumor regression scores (P = .001). Survival was strongly dictated by stage after neoadjuvant chemotherapy, rather than clinical stage at presentation.
  
  
  CONCLUSIONS
  The stage of esophageal or esophagogastric junction adenocarcinoma after neoadjuvant chemotherapy determines prognosis rather than the clinical stage before neoadjuvant chemotherapy, indicating the importance of focusing on postchemotherapy staging to more accurately predict outcome and eligibility for surgery. Patients who are downstaged by neoadjuvant chemotherapy benefit from reduced rates of local and systemic recurrence.
authors: Andrew R
authors: AR
authors: Davies
authors: James A
authors: JA
authors: Gossage
authors: Janine
authors: J
authors: Zylstra
authors: Fredrik
authors: F
authors: Mattsson
authors: Jesper
authors: J
authors: Lagergren
authors: Nick
authors: N
authors: Maisey
authors: Elizabeth C
authors: EC
authors: Smyth
authors: David
authors: D
authors: Cunningham
authors: William H
authors: WH
authors: Allum
authors: Robert C
authors: RC
authors: Mason
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D016208:Databases, Factual; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D016629:Esophagectomy / Q000379:methods; D004943:Esophagogastric Junction; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008131:London / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D016896:Treatment Outcome