Tumor regression in rectal cancer after intensified neoadjuvant chemoradiation: a morphometric and clinicopathological study

BACKGROUND High interobserver variation is a well known drawback of conventional tumor regression grading, and reaching consensus among pathologists may require a considerable effort. Therefore, in this study, morphometry was tried to assess tumor regression, and its prognostic role was explored. METHODS Tumor regression was quantified by a point counting method to yield tumor area fraction (TAF) as an index of remaining vital tumor. RESULTS In a series of 104 patients with clinically advanced rectal cancer treated with neoadjuvant radiochemotherapy, TAFs were distributed continuously towards complete regression which was observed in 8.7% of the cases. Plotting TAFs grouped by a conventional regression grading (Dworak's) revealed considerable overlap between groups. In a control series of untreated cancers, only TAFs of cancers with an expansive invasive border were setoff clearly from TAFs obtained for the study cases, but TAFs of control cases with an infiltrative invasive border and mucinous carcinomas extended well into the range of TAFs recorded for regressing tumors. Locoregional recurrence (N = 10) was significantly associated with perineural tumor infiltration and capsule transgressing lymph node metastasis/tumor deposits but not with the degree of tumor regression. Overall survival was better for patients with major regressions (≤20th percentile by morphometry, or Dworak regression grade (DRG) 4/5), although statistical significance was not reached. CONCLUSIONS Morphometry of tumor regression is feasible and explains why conventional regression grading is so difficult to perform. Assessment of tumor regression, by subjective grading or morphometry, does not appear to convey major prognostic information, at least not substantially beyond histopathological tumor staging. This observation discourages expending too much effort on developing this aspect of the pathomorphological workup of the resection specimens.