Is the pathological regression level of metastatic lymph nodes associated with oncologic outcomes following preoperative chemoradiotherapy in rectal cancer?

Abstract

PurposeThe oncologic impact of the lymph node (LN) regression level after preoperative chemoradiotherapy (PCRT) has not been thoroughly evaluated. Hence, this study aimed to examine whether the regression level of metastatic LNs following PCRT is associated with oncologic outcomes in rectal cancer.ResultsThe optimal number of cut points for LRG sum was determined to be three. The three LRG groups demonstrated different distributions according to the ypT and ypN stages (p < 0.001 for both). However, the distribution of the LRG groups was not associated with the TRG of the primary tumor (p = 0.527). The RFS significantly differed according to the LRG groups (p = 0.001). Moreover, the differences in RFS remained when the LRG groups were analyzed within each separate ypN stage. The LRG group was confirmed as a factor associated with RFS in the multivariate analysis (p=0.018), while the ypN stage was not (p=0.4).Patients and MethodsWe analyzed the outcomes of 142 rectal cancer patients diagnosed with ypN1 disease after PCRT followed by radical resection. The pathological responses of the primary tumor and LNs to PCRT were evaluated using the tumor regression grade (TRG) and LN regression grade (LRG), respectively. The impact of LRG on recurrence-free survival (RFS) was analyzed. The K-adaptive partitioning for survival data method was applied to determine the optimal number of cut points for the LRG-sum and the optimal number of subgroups.ConclusionThe LRG as an indicator of response to PCRT should be considered as a prognostic determinant in rectal cancer patients. Future large-scale prospective studies are needed to confirm this finding.

Effect of Responsiveness of Lymph Nodes to Preoperative Chemoradiotherapy in Patients With Rectal Cancer on Prognosis After Radical Resection

“…14,15 In contrast, others have indicated a response difference between the primary lesion and LNs. 11,[16][17][18] The present study showed that LRG had a correlation with TRG, although it was not found to be a stepwise correlation. The distribution of LRG-sum was strongly associated with total regression of the primary tumor.…”

“…We suggested the prognostic importance of pathologic regression levels of metastatic LNs after PCRT in patients with ypN1 disease in a previous report. 11 We extended the patient cohort to evaluate the prognostic effect of LRG overall in patients in the current study.…”

“…Pathologic responses to PCRT were evaluated in the resected specimens using the TRG system suggested by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists 13 : no evidence of irradiation change (fibrosis, necrosis, or vascular change) was defined as "no regression," dominant tumor mass with obvious irradiation change as "minimal regression," dominant irradiation change with residual tumor (easy to find) as "moderate regression," microscopic residual (difficult to find) tumor in fibrotic tissue as "near total regression," and no residual tumor cells, only fibrotic mass, as "total regression." The regression level of the metastatic LNs to PCRT was determined on the basis of the proportion of tumor cells as well as fibrosis and were classified into a 6-tier grading system 11 : pathologic LRG (pLRG). LN-preserving normal nodal architecture without evidence of cancer cells or fibrosis was scored as pLRG0, LN with 100% fibrosis as pLRG1, LN with <25% cancer cells as pLRG2, scattered glandular elements with fibrosis as pLRG3, LN with >50% cancer cells as pLRG4, and complete replacement with cancer cells as pLRG5.…”

“…There are, however, limited studies on the effects of PCRT on the histopathology of LNs in rectal cancer and its correlations with prognosis. 11,12 The correlation between primary tumor and LN regression level should be evaluated because the clinical diagnosis of the primary tumor regression level is used for surgical strategy decision after PCRT, such as local excision, or wait-and-watch strategies. The presence of regional metastatic LNs is a determinant for avoiding organ-preserving strategies; however, accuracy of imaging modality to diagnose LN metastasis is limited.…”

Prediction of tumor response of rectal cancer cells via 3D cell culture and in�vitro cytotoxicity assay before initiating preoperative chemoradiotherapy

“…In contrast, a study reported 28.5% lymph node positivity in patients who exhibited pCR (ypT0) (11). Moreover, Choi et al (33) demonstrated that lymph node regression grade (LRG) following preop-CRT was the only independent factor associated with relapse-free survival in patients with ypN-positive rectal cancer, who underwent preop-CRT. One of the interesting findings of this study was that the distribution of LRG was not associated with the TRG of the primary tumor, and that the LRG of each metastatic lymph node differed from the other within the same patient.…”