Can tumor regression grade influence survival outcome in ypT3 rectal cancer?

Locally advanced rectal cancer (LARC) patients achieving ypT3 status following neoadjuvant chemoradiation are considered to have poor response with minimal downstaging. However, residual cancer cell amounts vary in the subserosa/perirectal fat. Tumor regression grading (TRG) is an evaluation method based on the proportion of fibrosis and residual cancer cells. The aim of this study is to assess the influence of TRG in ypT3 rectal cancer patients who received neoadjuvant chemoradiation.

We retrospectively reviewed 325 LARC patients who received neoadjuvant chemoradiation and surgery. TRG scores were recorded by two independent pathologists. Among these patients, 143 were staged as ypT3. We analyzed TRG and other clinicopathological factors and their relationship with survival outcome including overall survival (OS) and disease-free survival (DFS).

Among 143 ypT3 patients, 44 (30.8 %) were TRG1, 84 (58.7 %) were TRG2 and 15 (10.5 %) were TRG3. Seventy-nine (55.3 %) of these patients had metastatic lymph nodes. In univariate analysis, TRG was not associated with DFS (TRG2 vs TRG1, P = 0.852; TRG3 vs TRG1, P = 0.593) or OS (TRG2 vs TRG1, P = 0.977; TRG3 vs TRG1, P = 0.665). Palliative surgery (HR 3.845; 95 % CI 1.670-8.857; P = 0.002) and metastatic lymph nodes after surgery (HR 5.894; 95 % CI 1.142-3.48; P = 0.015) were significantly associated with decreased DFS, while palliative surgery was the only factor associated with worse OS (HR 6.011; 95 % CI 2.150-16.810; P = 0.001). Palliative surgery (HR 3.923; 95 % CI 1.696-9.073; P = 0.001) and metastatic lymph nodes (HR 2.011; 95 % CI 1.152-3.512; P = 0.014) also showed prognostic significance for DFS in multivariate analysis.

Residual cancer cells evaluated by TRG score after neoadjuvant chemoradiation do not influence survival outcome in ypT3 rectal cancer patients. However, lymph node status is a significant prognostic factor in ypT3 patients.