title: Tumor regression grading after preoperative chemoradiotherapy for locally advanced rectal carcinoma revisited: updated results of the CAO/ARO/AIO-94 trial.
abstract: OBJECTIVE
  We previously described the prognostic impact of tumor regression grading (TRG) on the outcome of patients with rectal carcinoma treated with preoperative chemoradiotherapy (CRT) in the CAO/ARO/AIO-94 trial. Here we report long-term results after a median follow-up of 132 months.
  
  
  METHODS
  TRG after preoperative CRT was determined in 386 surgical specimens by the amount of viable tumor cells versus fibrosis, ranging from TRG 4 (no viable tumor cells) to TRG 0 (no signs of regression). Clinicopathologic parameters and TRG were correlated to the cumulative incidence of local recurrence, distant metastasis, and disease-free survival (DFS).
  
  
  RESULTS
  Ten-year cumulative incidence of distant metastasis and DFS were 10.5% and 89.5% for patients with TRG 4 (complete regression), 29.3% and 73.6% for TRG 2 and 3 (intermediate regression), and 39.6% and 63% for TRG 0 and 1 (poor regression), respectively (P = .005 and P = .008, respectively). On multivariable analysis, residual lymph node metastasis (ypN+) and TRG were the only independent prognostic factors for cumulative incidence of distant metastasis (P < .001 and P = .035, respectively) and DFS (P < .001 and P = .039, respectively), whereas local recurrence was significantly affected by ypN status (P < .001) and lymphatic invasion (P = .026).
  
  
  CONCLUSIONS
  Complete and intermediate tumor regressions were associated with improved long-term outcome in patients with rectal carcinoma after preoperative CRT independent of clinicopathologic parameters. This classification system needs to be prospectively tested in multiple data sets to validate its reproducibility in a wider setting.
authors.affiliation: Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria. emmanouil.fokas@kgu.de.
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Fokas
authors.affiliation: Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria.
authors.forename: Torsten
authors.initials: T
authors.lastname: Liersch
authors.affiliation: Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria.
authors.forename: Rainer
authors.initials: R
authors.lastname: Fietkau
authors.affiliation: Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Hohenberger
authors.affiliation: Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria.
authors.forename: Tim
authors.initials: T
authors.lastname: Beissbarth
authors.affiliation: Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria.
authors.forename: Clemens
authors.initials: C
authors.lastname: Hess
authors.affiliation: Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Becker
authors.affiliation: Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Ghadimi
authors.affiliation: Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria.
authors.forename: Karl
authors.initials: K
authors.lastname: Mrak
authors.affiliation: Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Merkel
authors.affiliation: Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria.
authors.forename: Hans-Rudolf
authors.initials: HR
authors.lastname: Raab
authors.affiliation: Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria.
authors.forename: Rolf
authors.initials: R
authors.lastname: Sauer
authors.affiliation: Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Wittekind
authors.affiliation: Emmanouil Fokas and Claus Rödel, University of Frankfurt, Frankfurt; Torsten Liersch, Tim Beissbarth, Clemens Hess, Heinz Becker, and Michael Ghadimi, University Medical Center Göttingen, Göttingen; Rainer Fietkau, Werner Hohenberger, Susanne Merkel, and Rolf Sauer, University of Erlangen, Erlangen; Hans-Rudolf Raab, Oldenburg Hospital, Oldenburg; Christian Wittekind, University Hospital Leipzig, Leipzig, Germany; and Karl Mrak, Krankenhaus der Barmherzigen Brüder, St Veit, Austria.
authors.forename: Claus
authors.initials: C
authors.lastname: Rödel
mesh_terms: D002277:Carcinoma / Q000401:mortality / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005355:Fibrosis; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000401:mortality; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D016016:Proportional Hazards Models; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D012074:Remission Induction; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome