title: Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esophageal squamous cell carcinoma: final report of a randomized, controlled trial of preoperative chemotherapy versus surgery alone.
abstract: BACKGROUND
  Surgery is the standard treatment for patients with resectable esophageal carcinoma, but the long term prognosis of these patients is unsatisfactory. Some randomized trials of preoperative chemotherapy suggest that the prognosis of patients who respond may be improved.
  
  
  METHODS
  This randomized, controlled trial compared patients with clinically resectable esophageal epidermoid carcinoma who underwent surgery alone (Arm A) with those who received preoperative chemotherapy (Arm B). Overall survival and the prognostic impact of major response to chemotherapy were analyzed. Forty-eight patients were enrolled in each arm. Chemotherapy consisted of two or three cycles of cisplatin (100 mg/m2 on Day 1) and 5- fluorouracil (1000 mg/m2 per day continuous infusion on Days 1-5). In both study arms, transthoracic esophagectomy plus two-field lymphadenectomy was performed. The two groups were comparable in terms of patient characteristics.
  
  
  RESULTS
  Forty-seven patients were evaluable in each arm. The curative resection rate was 74.4% (35 of 47 patients) in Arm A and 78.7% (37 of 47 patients) in Arm B. Treatment-related mortality was 4.2% in both arms. The response rate to preoperative chemotherapy was 40% (19 of 47 patients), including 6 patients (12.8%) who achieved a pathologic complete responses. Overall survival was not improved significantly. The 19 patients in Arm B who responded to chemotherapy and underwent curative resection had significantly better 3-year and 5-year survival rates (74% and 60%, respectively) compared with both nonresponders (24% and 12%, respectively; P = 0.0002) and patients in Arm A who underwent complete resection (46% and 26%, respectively; P = 0.01): Patients who achieved a pathologic complete response (P = 0.01), but not those who achieved a partial response (P = 0.2), had significantly improved survival.
  
  
  CONCLUSIONS
  Patients with resectable esophageal carcinoma who underwent preoperative chemotherapy and obtained a pathologic complete response had a significantly improved long term survival. Major efforts should be undertaken to identify patients before neoadjuvant treatments who are likely to respond.
authors.affiliation: Clinica Chirurgica 4', University of Padova School of Medicine-Azienda Ospedaliera di Padova, Padova, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Ancona
authors.forename: A
authors.initials: A
authors.lastname: Ruol
authors.forename: S
authors.initials: S
authors.lastname: Santi
authors.forename: S
authors.initials: S
authors.lastname: Merigliano
authors.forename: V C
authors.initials: VC
authors.lastname: Sileni
authors.forename: H
authors.initials: H
authors.lastname: Koussis
authors.forename: G
authors.initials: G
authors.lastname: Zaninotto
authors.forename: L
authors.initials: L
authors.lastname: Bonavina
authors.forename: A
authors.initials: A
authors.lastname: Peracchia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D002945:Cisplatin; D005472:Fluorouracil