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Patients With Curative Resection of cT3-4 Rectal Cancer After Preoperative Radiotherapy or Radiochemotherapy: Does Anybody Benefit From Adjuvant Fluorouracil-Based Chemotherapy? A Trial of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group

Laurence Collette, Jean-Francois Bosset, Marcel den Dulk, France Nguyen, Laurent Mineur, Philippe Maingon, Ljiljana Radosevic-Jelic, Marianne Piérart, Gilles Calais

From the Statistics Department, European Organisation for Research and Treatment of Cancer Data Center, Brussels, Belgium; Department of Radiation Therapy, University of Franche-Comté, Besançon; Department of Radiation Therapy, Clinic Sainte-Catherine, Avignon; Department of Radiation Therapy, Cancer Center Dijon, Dijon; Department of Radiation Therapy, University François Rabelais, Tours, France; Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands; and Institute for Oncology and Radiology, Belgrad, Serbia

Address reprint requests to Laurence Collette, MSc, PhD, European Organisation for Research and Treatment of Cancer (EORTC), Department of Statistics, Avenue E. Mounier 83/11, B-1200 Bruxelles, Belgium; e-mail: laurence.collette{at}eortc.be

Purpose European Organisation for Research and Treatment of Cancer (EORTC) trial 22921 compared adjuvant fluorouracil-based chemotherapy (CT) to no adjuvant treatment in a 2 x 2 factorial trial with randomization for preoperative (chemo)radiotherapy in patients with resectable T3-4 rectal cancer. The results showed no significant impact of adjuvant CT on progression-free or overall survival, although a difference seemed to emerge at approximately, respectively, 2 and 5 years after the start of preoperative treatment. We further explored the data with the aim of refining our understanding of the long-term results.

Patients and Methods Data of 785 of the 1,011 randomly assigned patients who whose disease was M0 at curative surgery were used. Using meta-analytic methods, we investigated the homogeneity of the effect of adjuvant CT on the time to relapse or death after surgery (disease-free survival [DFS]) and survival in patient subgroups.

Results Although there was no statistically significant impact of adjuvant CT on DFS for the whole group (P > .5), the treatment effect differed significantly between the ypT0-2 and the ypT3-4 patients (heterogeneity P = .009): only the ypT0-2 patients seemed to benefit from adjuvant CT (P = .011). The same pattern was observed for overall survival.

Conclusion Exploratory analyses suggest that only good-prognosis patients (ypT0-2) benefit from adjuvant CT. This could explain why, in the whole group, the progression-free and overall survival diverged only after the poor-prognosis patients (ypT3-4) had experienced treatment failure. Patients in whom no downstaging was achieved did not benefit. This also suggests that the same prognostic factors may drive both tumor sensitivity for the primary treatment and long-term clinical benefit from further adjuvant CT.

Supported by Grant Nos. 2U10-CA11488-21 through 5U10 CA11488-35 from the National Cancer Institute, by Programme Hospitalier de Recherche Clinique (PHRC 1992-France) and by the Ligue Contre le Cancer Comité du Doubs. M.D. is supported by a Quality Assurance Fellowship of the European Society of Surgical Oncology.

Presented in an oral session of the 13th European Cancer Conference, October 30-November 3, 2005, Paris, France.

The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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• Adjuvant Management of Rectal Cancer: The More We Learn, the Less We Know
  Bruce D. Minsky
  JCO 2007 25: 4339-4340 [Full Text]

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• Adjuvant Chemotherapy Following Neoadjuvant Therapy of Rectal Cancer: The Type of Neoadjuvant Therapy (chemoradiotherapy or radiotherapy) May Be Important for Selection of Patients
  Rainer Fietkau and Gunther Klautke
  JCO 2008 26: 507-508 [Full Text]

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