Histologic response grading after chemoradiation in locally advanced rectal cancer: a proposal for standardized reporting.

In a previous editorial, we criticized pathological complete response (pCR) as an endpoint in rectal cancer after neoadjuvant chemoradiation, because only a small proportion of patients (10–20%) are captured by a pCR. We also pointed out the confusion as to what constitutes a pCR: ypT0 alone, ypT0 plus ypTmic, or ypT0 plus ypN0. Further confusion arises from authors who define a pCR as ‘‘the presence of residual cells, which are considered non-viable’’ (1), and ‘‘no evidence of viable malignant cells in the specimen or the presence of scattered isolated malignant cells in a background of fibrosis’’ (2). The evaluation of clinical response is recognized to be inaccurate. Standard response criteria in terms of size according to the World Health Organization or Response Evaluation Criteria in Solid Tumors criteria do not take into account minor responses. There is poor differentiation on imaging of residual areas within the radiation field to distinguish viable tumor from replacement with fibrosis, and clinical response has not been shown to act as a robust surrogate endpoint to predict outcome in this setting. If we had an objective, practical and clinically relevant regression classification system, which encompassed both the degree of damage sustained by the tumor and the residual tumor burden in primary and nodes, then we could precisely compare the efficacy of various treatment protocols—either in terms of the cytotoxic drugs or radiation dose. We could also expect to squeeze more relevance from a molecular response prediction. Hence, alternative strategies to categorize treatment effects from radiation and chemoradiation describe the observed histologic changes in the resected specimen. Measures such as T-microscopic (Tmic), and tumor regression grades (TRGs), define other less-marked levels of response, apart from pCR, although they are not yet recognized in the Amer-