Comparison of Tumor Regression Grade Systems for Locally Advanced Rectal Cancer After Multimodality Treatment

Abstract

Tumor regression grade (TRG) is a measure of histopathological response of rectal cancer to neoadjuvant chemoradiation and is associated with outcomes. Several TRG systems are used: Mandard (5,3-tier), Dowrak/Rödel (5,3-tier), Memorial Sloan Kettering Cancer Center (MSKCC), and American Joint Committee on Cancer (AJCC) Cancer Staging. A single measure of rectal cancer response would assist in comparing results across institutions, and in designing future rectal cancer studies. In this study, the predictive accuracies of the various published classification schemes are compared. Review of a prospective database identified 563 patients with locally advanced rectal cancer (T3/4 and/or N1) treated between 1998 and 2007 with long-course chemoradiation and total mesorectal excision. TRG was determined by measuring proportion of tumor mass replaced by fibrosis. Patients were classified into TRG schemes, which were compared by analyzing association with recurrence and survival using concordance index. Probabilities of recurrence-free survival were estimated using the Kaplan-Meier method. All statistical tests were two-sided. All TRG systems were predictive of recurrence. Concordance indices of the three-tier Mandard, three-tier Dowrak/Rödel, three-tier MSKCC, and four-tier AJCC systems were: 0.665, 0.653, 0.683, and 0.694, respectively (higher number = better prediction). The AJCC system more accurately predicted recurrence than the three-tier Mandard (P = .002) or Dowrak/Rödel (P = .006) and had a higher concordance index than MSKCC, although this did not reach statistical significance (P = .068). When classifying rectal cancer response to chemoradiation, the AJCC Staging Manual (7(th) edition) system is most accurate and should be adopted as the standard.