Published online Feb 28, 2017. doi: 10.3748/wjg.v23.i8.1412
Peer-review started: October 25, 2016
First decision: December 19, 2016
Revised: December 29, 2016
Accepted: January 17, 2017
Article in press: January 17, 2017
Published online: February 28, 2017
To clarify which factors may influence pathological tumor response and affect clinical outcomes in patients with locally advanced rectal carcinoma treated with neo-adjuvant chemoradiotherapy and surgery.
Tumor regression grade (TRG) according to the Dworak system and yTNM stage were assessed and correlated with pre-treatment clinico-pathological variables in 215 clinically locally advanced (cTNM stage II and III) rectal carcinomas. Prognostic value of all pathological and clinical factors on disease free survival (DFS) and cancer specific survival (CSS) was analyzed by Kaplan Meier and Cox-regression analyses.
cN+ status, mucinous histotype or poor differentiation in the pre-treatment biopsy were significantly associated with lower pathological response (low Dworak grade and TNM remaining unchanged/upstaging). Cases showing acellular mucin pools in surgical specimens all had unremarkable clinical courses with no deaths or recurrences during follow-up. Dworak grade had prognostic significance for DFS and CSS. However, compared to the 5-tiered system, a simplified two-tiered grading system, in which grades 0, 1 and 2 were grouped as absent/partial regression and grades 3 and 4 were grouped as total/subtotal regression, was more reproducible and prognostically informative. The two-tiered Dworak system, yN stage, craniocaudal extension of the tumor and radial margin status were significant independent prognostic variables.
Our data suggest that caution should be applied in using a conservative approach in rectal carcinomas with cN+ status, extensive/lower involvement of the rectum and mucinous histotype or poor differentiation. Although Dworak TRG is prognostically significant, a simplified two-tiered system could be preferable. Finally, cases with acellular mucin pools should be carefully evaluated to definitely exclude residual mucinous carcinoma.
Core tip: This study evaluates the prognostic significance of clinico-pathological variables in patients with locally advanced rectal carcinoma treated with neo-adjuvant chemo-radiotherapy (CRT) and surgery. Our data show that tumors with cN+ status, extensive/lower involvement of the rectum, mucinous histotype and poor differentiation have a lower response to pre-operative CRT. Dworak tumor regression grade was prognostically informative; however, a simplified two-tiered system was more reproducible and prognostically significant. Acellular mucin pools were found in a percentage of cases with excellent outcomes. Although acellular mucin pools should be considered as complete pathological responses, careful histological examination is mandatory to exclude residual mucinous carcinoma.