Prognostic influence of histopathological regression patterns in rectal adenocarcinoma receiving neoadjuvant therapy

Abstract

Results: A total of 183 patients from two hospitals. The concordance rate between pathologists was good. In total, 18% of the patients showed grade 0 (complete response), 31.7% grade 1, 19.2% grade 2 and 31.1% grade 3 regression. T down-staging was found in 51.9% of the cases. 46 patients recurred and 18 died of disease (median follow-up time: 39 months). We found a statistically significant association between pathological response and pT stage and down-staging. Inflammatory reaction in the tumor bed was significantly associated to regression and prognosis. Cox's multivariate analysis of survival revealed that down-staging and presence of mucin pools in the tumor bed behaved as significant predictors of recurrence and regression grade and mucin pools as significant predictors of survival.Conclusions: Pathological response is an important surrogate marker of prognosis in some large series, but results are varying. There are many systems to grade regression and this makes it difficult to compare the results by different groups. It is important to report the specific pattern of response, for some of them may have prognostic relevance. We feel there is an urgent need to develop standarized protocols and employ a universal regression scheme if we intend to use this factor to guide therapy.

How to measure tumour response in rectal cancer? An explanation of discrepancies and suggestions for improvement

“…Dworak grade 2, where shrinkage is the main form of regression. This is in line with findings of Fernandez-Acenero [70], who showed that fragmentation was indeed the main pattern of response in the near-complete response group (58%), and that the presence of fragmentation was linked to the absence of downstaging. We can only hypothesize about the more complex interpretation of this reaction pattern and the poor outcome.…”

“…The limited size of the fragments is below the power of resolution on imaging and surgical treatment might be irradical, resulting in local recurrences. Three recent studies (289 patients with locally advanced rectal cancer) [68][69][70] showed that fragmentation was present in 40% of cases, while in a study of 45 cT3 patients from Cleveland [44] 80% of cases showed fragmented response. Fragmentation or scattering of tumour cells also causes a clear discrepancy between macroscopy and microscopy [71].…”

“…In a careful description of the findings in 27 patients (49%), it was shown that fragments could be found up to 3 cm from the ulcer, in all directions (proximal, distal and lateral). Fragmentation is associated with more frequent residual lymph node metastases, less downstaging, positive resection margins and a poor outcome [68][69][70]. When TRG was applied to these cases [69], there was no prognostic impact.…”

“…In patients with a complete pathological response, 27% of patients present with acellular mucin pools [73], while in all stages this was between 12 and 35% [70,[74][75][76][77]. The presence of acellular mucin pools in pCR patients does not affect prognosis [73], while some studies suggest better outcome for all stages in the presence of mucin pools [70,74,75]. In contrast, presence of remaining tumour cells in mucin pools is associated with poor outcome [74].…”

“…Local regrowth in smaller tumours (cT1/T2) was significantly lower, 19%. In the five series [44,[68][69][70][71] that describe fragmentation as a response mechanism (total number of patients 460), only limited information is presented about stage in relation to response mechanism. Early stage tumours (cT2) show fragmentation in 25% compared to 44% in cT3 tumours [68].…”