title: Surgical quality and nodal ultrastaging is associated with long-term disease-free survival in early colorectal cancer: an analysis of 2 international multicenter prospective trials.
abstract: BACKGROUND
  The National Quality Forum has endorsed a minimum of 12 lymph node (LN) as a surrogate measure of quality in colorectal cancer (CRC). The prognostic value of ultrastaging hematoxylin and eosin (H&E) negative LNs (N0) using pan-cytokeratin immunohistochemistry (pan-CK-IHC) is unknown.
  
  
  OBJECTIVE
  To assess the effect on survival of surgical quality and focused pathologic analysis.
  
  
  METHODS
  Between 2001 and 2007, 253 evaluable patients with resectable CRC were enrolled. Multiple sectioning and pan-CK-IHC were performed on N0 LNs (American Joint Commission on Cancer Stage II). Follow-up was performed at 6-month intervals with a 4-year disease-free survival (DFS) primary end-point.
  
  
  RESULTS
  There were 253 patients, 177 N0 and 76 N1/N2 patients, staged conventionally. Thirty-six (20%) N0 patients were upstaged using ultrastaging (N0-->N0i+ [n = 27] and N0-->N1mi [n = 9]). At a mean follow-up of 3.4 +/- 1.6 years, 38 (15%) have recurred. Only 3% (3/108) of patients with > or =12 LNs, negative by H&E and pan-CK-IHC (N0i-), compared with 18% (6/33) with <12 LNs/N0i- (6/33; P = 0.0015) have recurred. Four-year DFS differed significantly according to surgical quality (<12 vs. > or =12 LNs) among Stage II patients only (DFS, <12 vs. > or =12 LNs: Stage I, 90.5% vs. 97.7%, P = 0.22; Stage II, 67.5% vs. 94.7%, P = 0.0036; Stage III, 61% vs. 61%, P = 0.61).
  
  
  CONCLUSIONS
  This represents the first prospective report demonstrating that both surgical quality and nodal ultrastaging impacts survival in Stage II CRC. Patients with Stage II CRC having > or =12 LNs negative for micrometastases (N0i-) are likely cured by surgery alone. Both surgical and pathologic quality measures are imperative in early CRC to improve patient selection for adjuvant chemotherapy.
authors.affiliation: California Oncology Research Institute, University of California, Los Angeles, CA 90404, USA. abilchik@mednet.ucla.edu
authors.forename: Anton
authors.initials: A
authors.lastname: Bilchik
authors.forename: Aviram
authors.initials: A
authors.lastname: Nissan
authors.forename: Zev
authors.initials: Z
authors.lastname: Wainberg
authors.forename: Perry
authors.initials: P
authors.lastname: Shen
authors.forename: Martin
authors.initials: M
authors.lastname: McCarter
authors.forename: Mladjan
authors.initials: M
authors.lastname: Protic
authors.forename: Robin
authors.initials: R
authors.lastname: Howard
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.forename: Josh
authors.initials: J
authors.lastname: Tyler
authors.forename: George E
authors.initials: GE
authors.lastname: Peoples
authors.forename: Alexander
authors.initials: A
authors.lastname: Stojadinovic
mesh_terms: D000368:Aged; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000601:surgery*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016015:Logistic Models; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging / Q000379:methods*; D011379:Prognosis; D011446:Prospective Studies; D011787:Quality of Health Care; D013194:Staining and Labeling; D018709:Statistics, Nonparametric