Originally published as JCO Early Release 10.1200/JCO.2005.02.1329 on October 24 2005

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Prognostic Significance of Tumor Regression After Preoperative Chemoradiotherapy for Rectal Cancer

From the Department of Radiation Therapy, Department of Surgery, and Institute of Pathology, University of Erlangen, Erlangen; Institute of Medical Informatics, Biometry and Epidemiology, Charité University Medicine, Berlin; Department of Pathology, University Hospital Göttingen; Germany Department of Surgery, University of Göttingen, Göttingen; Department of Radiation Therapy, University of Rostock, Rostock; Department of Surgery, Klinikum Oldenburg, Oldenburg; Institute of Pathology, University of Leipzig, Leipzig, Germany; and Department of Pathology, Kaiser-Franz-Josef Hospital, Vienna, Austria

Address reprint requests to Claus Rödel, MD, Department of Radiation Therapy, Universitätsstr 27, D-91054 Erlangen, Germany; e-mail: claus.roedel{at}strahlen.med.uni-erlangen.de

PURPOSE: We assessed the impact of tumor regression grading (TRG) and its value in correlation to established prognostic factors in a cohort of rectal carcinoma patients treated by preoperative chemoradiotherapy (CRT).

PATIENTS AND METHODS: TRG was evaluated on surgical specimens of 385 patients treated within the preoperative CRT arm of the CAO/ARO/AIO-94 trial: 50.4 Gy was delivered, fluorouracil was given in the first and fifth week, and surgery was performed 6 weeks thereafter. TRG was determined by the amount of viable tumor versus fibrosis, ranging from TRG 4 when no viable tumor cells were detected, to TRG 0 when fibrosis was completely absent. TRG 3 was defined as regression more than 50% with fibrosis outgrowing the tumor mass, TRG 2 was defined as regression less than 50%, and TRG 1 was defined basically as a morphologically unaltered tumor mass. We performed an initially unplanned, hypothesis-generating analysis with respect to the prognostic value of this TRG system.

RESULTS: TRG 4, 3, 2, 1, 0 was found in 10.4%, 52.2%, 13.8%, 15.3%, and 8.3% of the resected specimens, respectively. Five-year disease-free survival (DFS) after CRT and curative resection was 86% for TRG 4, 75% for grouped TRG 2 + 3, and 63% for grouped TRG 0 + 1 (P = .006). On multivariate analysis, the pathologic T category and the nodal status after CRT were the most important independent prognostic factors for DFS.

CONCLUSION: In this exploratory analysis, complete (TRG 4) and intermediate pathologic response (TRG 2 + 3) suggested improved DFS after preoperative CRT. TRG assessment should be implemented in pathologic evaluation and prospectively validated in further studies.

Supported by Grant No. 70-578 from Deutsche Krebshilfe.

Presented in part at the 46th Annual Meeting of the American Society of Therapeutic Radiology and Oncology, October 3-7, 2004, Atlanta, GA; and at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL.

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

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