College of American Pathologists Tumor Regression Grading System for Long-Term Outcome in Patients with Locally Advanced Rectal Cancer

Abstract

Background The National Comprehensive Cancer Network's Rectal Cancer Guideline Panel recommends American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) system to evaluate pathologic response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Yet, the clinical significance of the AJCC/CAP TRG system has not been fully defined. Materials and Methods This was a multicenter, retrospectively recruited, and prospectively maintained cohort study. Patients with LARC from one institution formed the discovery set, and cases from external independent institutions formed a validation set to verify the findings from discovery set. Overall survival (OS), disease‐free survival (DFS), local recurrence‐free survival (LRFS), and distant metastasis‐free survival (DMFS) were assessed by Kaplan‐Meier analysis, log‐rank test, and Cox regression model. Results The discovery set (940 cases) found, and the validation set (2,156 cases) further confirmed, that inferior AJCC/CAP TRG categories were closely /ccorrelated with unfavorable survival (OS, DFS, LRFS, and DMFS) and higher risk of disease progression (death, accumulative relapse, local recurrence, and distant metastasis) (all p < .05). Significantly, pairwise comparison revealed that any two of four TRG categories had the distinguished survival and risk of disease progression. After propensity score matching, AJCC/CAP TRG0 category (pathological complete response) patients treated with or without adjuvant chemotherapy displayed similar survival of OS, DFS, LRFS, and DMFS (all p > .05). For AJCC/CAP TRG1–3 cases, adjuvant chemotherapy treatment significantly improved 3‐year OS (90.2% vs. 84.6%, p < .001). Multivariate analysis demonstrated the AJCC/CAP TRG system was an independent prognostic surrogate. Conclusion AJCC/CAP TRG system, an accurate prognostic surrogate, appears ideal for further strategizing adjuvant chemotherapy for LARC. Implications for Practice The National Comprehensive Cancer Network recommends the American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) four‐category system to evaluate the pathologic response to neoadjuvant treatment for patients with locally advanced rectal cancer; however, the clinical significance of the AJCC/CAP TRG system has not yet been clearly addressed. This study found, for the first time, that any two of four AJCC/CAP TRG categories had the distinguished long‐term survival outcome. Importantly, adjuvant chemotherapy may improve the 3‐year overall survival for AJCC/CAP TRG1–3 category patients but not for AJCC/CAP TRG0 category patients. Thus, AJCC/CAP TRG system, an accurate surrogate of long‐term survival outcome, is useful in guiding adjuvant chemotherapy management for rectal cancer.

ARID1A knockdown enhances carcinogenesis features and aggressiveness of Caco-2 colon cancer cells: An in vitro cellular mechanism study

“…The cancer cells are usually graded based on degree of their differentiation [27][28][29]. The cells that are well organized and apparently similar to the normal cells are defined as low-grade (well-differentiated) cells, whereas those with disorganization are defined as high-grade (poor-differentiated or undifferentiated) cells.…”

“…The cells that are well organized and apparently similar to the normal cells are defined as low-grade (well-differentiated) cells, whereas those with disorganization are defined as high-grade (poor-differentiated or undifferentiated) cells. In addition, the poor-differentiated grade is associated with the aggressive behaviors of cancer cells [27][28][29]. Aggressiveness of the cancer cells is characterized by chemoresistance toward various chemotherapy agents, increased cell proliferation, migration, invasion, etc.…”

Molecular and Dynamic Evaluation of Proteins Related to Resistance to Neoadjuvant Treatment with Chemoradiotherapy in Circulating Tumor Cells of Patients with Locally Advanced Rectal Cancer

“…Important studies have demonstrated the relevance of pCR, as an outcome that must be achieved in NCRT, as it is associated with good DFS and 5-year OS [ 11 , 40 ]. For patients with pCR, especially for tumors of the distal rectum, the WW strategy is quite attractive and safe [ 10 , 41 ].…”

Comparison of tumor regression grading systems for locally advanced gastric adenocarcinoma after neoadjuvant chemotherapy

“…Therefore, when verifying the prognostic value of the histological response, considerable work should be done on determining an optimal tumor response classification for GC. Currently, two major principles are common to these systems for grading tumor regression: (1) estimating residual tumor in relation to fibrotic changes, e.g., the Mandard, AJCC/CAP, and Dworak systems[ 17 , 18 , 30 ]; and (2) proportioning the residual tumor in relation to the previous tumor site, e.g., the Becker and JGCA system[ 16 , 31 ]. Although both are semiquantitative principles, the use of different systems reveals great regional disparities.…”

“…The extent of regressive tumors was evaluated and recorded according to: (1) The amount of viable tumor vs fibrotic tissue, which ranged from a total lack of tumor regression to complete response with no viable tumor identified; and (2) The percentage of the viable residual tumor, which was calculated by dividing the viable residual tumor area by the total tumor area. Tumor regression grades were then allocated according to the JGCA2017, JGCA, Becker, AJCC/CAP, and Mandard systems (Table 1 )[ 7 , 8 , 16 - 18 ]. As for the tumor regression grade, the JGCA2017 criteria example for each grade is shown in Figure 1 .…”