title: Downstage migration after neoadjuvant chemoradiotherapy for rectal cancer: the reverse of the Will Rogers phenomenon?
abstract: Downstaging after neoadjuvant treatment is increasingly used as a prognostic factor and surrogate endpoint in clinical trials. However, in recent trials of neoadjuvant 5-fluorouracil-based chemoradiotherapy for rectal cancer, downstaging did not translate into a benefit with regard to either disease-free survival (DFS) or overall survival. By analyzing the 10-year outcome data of the German CAO/ARO/AIO-94 phase 3 trial, the authors demonstrated that significantly fewer patients had poor prognostic features (eg, ypT3-4, ypN1-2) after preoperative 5-fluorouracil-based chemoradiotherapy. Nevertheless, these patients with International Union for Cancer Control stage II disease were found to be at a higher risk of developing distant metastases and had poorer DFS compared with patients with corresponding TNM tumor (sub)groups in the postoperative treatment arm, whereas patients with International Union for Cancer Control stage III disease demonstrated a nonsignificant trend toward a worse outcome after preoperative treatment. Overall, DFS remained identical in both treatment arms. Thus, "downstage migration" after neoadjuvant treatment resembles the reverse of the Will Rogers phenomenon and therefore may not be a reliable endpoint for long-term outcomes.
authors.affiliation: Department of Radiotherapy and Oncology, University of Frankfurt, Frankfurt, Germany.
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Fokas
authors.affiliation: Department of General Surgery, University Medical Center Gottingen, Gottingen, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Liersch
authors.affiliation: Department of Radiation Therapy, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Fietkau
authors.affiliation: Department of Surgery, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Hohenberger
authors.affiliation: Department of Radiotherapy, University Medical Center Gottingen, Gottingen, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Hess
authors.affiliation: Department of General Surgery, University Medical Center Gottingen, Gottingen, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Becker
authors.affiliation: Department of Radiation Therapy, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Sauer
authors.affiliation: Institute of Pathology, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Wittekind
authors.affiliation: Department of Radiotherapy and Oncology, University of Frankfurt, Frankfurt, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Rödel
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D059186:Chemoradiotherapy, Adjuvant; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D023381:Endpoint Determination; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D016032:Randomized Controlled Trials as Topic; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D016896:Treatment Outcome
chemical_list: D005472:Fluorouracil
keywords: chemoradiotherapy; downstage migration; long-term follow-up; phase 3 trial; rectal cancer; reverse Will Rogers phenomenon