T3N0 대장직장암에서 림프혈관침습이 보조항암요법 결정에 미치는 중요성과 효용성 및 대체인자

Abstract

Background: Unlike in advanced colorectal cancer stages like stage III, adjuvant chemotherapy application in T3N0 colorectal cancer is consistently on debates. Lymphovascular invasion (LVI), known as a major prognostic factor in colorectal cancer, is also as one of the high-risk features that guide adjuvant chemotherapy. This study aimed to evaluate the prognostic importance and reliability of LVI as an adjuvant chemotherapy indicator in patients with T3N0 colorectal cancer and analyze the impact of adjuvant chemotherapy on oncologic outcomes in these patients. Material and Methods: We included 1634 patients with pathologically proven T3N0 colorectal cancer who underwent curative radical resection at Asan Medical Center, Seoul, Korea between January 2012 and December 2016. For review cohort of 242 patients, pathologic slide review including dual immunohistochemistry with D2-40 and CD 31 to identify lymphatic and vascular invasion, was performed. Changes on the reviewed LVI status after dual immunohistochemical stain (rLVI) were evaluated. The rLVI included small blood and lymphatic vessel invasion and large vessel invasion. Revised LVI (ReLVI) excluded large vessel invasion after rLVI was distributed. The association between high-risk features including perineural invasion, preoperative obstruction, resection margin involvement, and redistributed LVI that indicated adjuvant chemotherapy, as well as adjuvant chemotherapy with recurrence free survival (RFS) and overall survival (OS) for the overall and review cohort were analyzed. Results: In the overall cohort, 772 patients received adjuvant chemotherapy. Among chemotherapy group, 179 patients (23.2%) had LVI as the only high-risk feature. LVI and perineural invasion (PNI) were found in 384 (23.5%) and 272 patients (16.5%), respectively, in the overall cohort. The 5-year RFS was 92% and 5-year OS was 91.4%. High-risk features such as preoperative obstruction, PNI, and positive margins were significantly associated with RFS and OS. Adjuvant chemotherapy and LVI were not associated with RFS (p=0.593) or OS (p=0.218). In the review cohort, the diagnosis of LVI was changed in 82 (33.2%) and that of PNI was changed in 25.2% of the patients. LVI and large vessel invasion were not associated with RFS and OS. The rLVI only showed relationship with RFS in the univariate study while reLVI which excludes large vessel invasion did not. Conclusions: In this cohort of patients with T3N0 colorectal cancer, the prognostic importance of LVI is not defined and may cause diagnostic inaccuracy and low recurrence rate prediction. There might be a need to reconsider LVI as a guiding sign for adjuvant chemotherapy and consensus on detailed definition.