title: Classification of pathologic response to neoadjuvant therapy in esophageal and junctional cancer: assessment of existing measures and proposal of a novel 3-point standard.
abstract: OBJECTIVE
  To assess existing measures of pathologic response to neoadjuvant therapy in esophageal and junctional cancer, and to recommend an optimum classification.
  
  
  BACKGROUND
  Multimodal therapy is increasingly the standard of care for locally advanced esophageal cancer. Numerous measures of pathologic response have been studied; however, no international standardization exists and no measure is incorporated into the current American Joint Committee on Cancer staging system.
  
  
  METHODS
  A total of 393 consecutive patients completing multimodal therapy were studied, all with prospectively recorded Mandard tumor regression grades (TRG). Seven other published methods of response were compared, and a novel 3-point TRG [TRG 1 (complete); TRG 2/3 (partial); TRG 4/5 (none/minimal)] was tested. Clinical and pathologic evidence of nodal regression was assessed in a consecutive subset of 200 comprehensively staged patients.
  
  
  RESULTS
  All models had similar discriminatory and stratification power, and they predicted survival (P < 0.0001) on univariate analysis. Conversely, only the 3-point TRG (P = 0.042) along with ypN (P < 0.001) and ypT stage (P < 0.001) independently predicted survival. The median survival for TRG 1 was 71 months compared with 30 and 17 months for TRG 2/3 and TRG 4/5, respectively (P < 0.0001). Apparent complete nodal response (cN1 to ypN0) was seen in 64% of the TRG 1 group, 30% of the TRG 2/3 group, and 5% of the TRG 4/5 group (P < 0.0001).
  
  
  CONCLUSIONS
  No existing response measure independently predicts outcome. A complete response (TRG 1) defines a unique cohort after neoadjuvant therapy, associated closely with nodal response, and overall survival. This classification merits consideration for standardization of treatment response, and for inclusion in staging nomenclature.
authors.affiliation: *Department of Surgery, Trinity Centre for Health Sciences, Trinity College Dublin, and St James Hospital †Department of Biostatistics, University College Dublin ‡Department of Pathology, St James Hospital, Dublin, Ireland.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Donohoe
authors.forename: Naoimh J
authors.initials: NJ
authors.lastname: O'Farrell
authors.forename: Tim
authors.initials: T
authors.lastname: Grant
authors.forename: Sinead
authors.initials: S
authors.lastname: King
authors.forename: Lindsey
authors.initials: L
authors.lastname: Clarke
authors.forename: Cian
authors.initials: C
authors.lastname: Muldoon
authors.forename: John V
authors.initials: JV
authors.lastname: Reynolds
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000628:therapy*; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000628:therapy*; D003952:Diagnostic Imaging; D004938:Esophageal Neoplasms / Q000473:pathology* / Q000628:therapy*; D016629:Esophagectomy / Q000379:methods; D004943:Esophagogastric Junction / Q000473:pathology*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome