Rocco Cappellesso1, Lorenzo Nicolè1, Francesca Zanco1, Marcello Lo Mele1, Ambrogio Fassina1, Laura Ventura2, Erik Rosa-Rizzotto3, Ennio Guido3, Franca De Lazzari3, Pierluigi Pilati4, Marco Tonello5, Matteo Fassan6, Massimo Rugge1. 1. Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Padua 35121, Italy. 2. Department of Statistics, University of Padua, Padua 35121, Italy. 3. Gastroenterology Unit, S. Antonio Hospital, Padua 35128, Italy. 4. Unit of Surgical Oncology of the Esophagus and Digestive Tract, Veneto Institute of Oncology - I.R.C.S.S, Padua 35128, Italy. 5. Unit of Surgical Oncology of the Esophagus and Digestive Tract, Veneto Institute of Oncology - I.R.C.S.S, Padua 35128, Italy; Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padua, Padua 35128, Italy. 6. Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Padua 35121, Italy. Electronic address: matteo.fassan@unipd.it.
Abstract
BACKGROUND: The population screening campaigns have resulted in increasing the prevalence of endoscopically resected colorectal cancers (CRCs) invading the submucosa (pT1). Synchronous nodal involvement occurs in less than 15 % of these tumors. Histologic criteria currently used for selecting patients needing resection are imprecise and most patients could have been simply followed-up. Tumor infiltrating lymphocytes (TILs) and mismatch repair (MMR) status impact on CRC prognosis. To identify patients requiring completion surgery, the value of histologic variables, TILs and MMR status as risk factors of nodal metastasis was investigated in screening detected and endoscopically removed pT1 CRCs. METHODS: In 102 endoscopically resected pT1 CRCs, the cancer phenotype, CD3+ and CD8+ TILs, and MMR status were assessed. Univariate and multivariate analyses were used to evaluate the correlation with nodal metastasis. RESULTS: Positive resection margin, evidence of vascular invasion and tumor budding, wide area of submucosal invasion, and high number of CD3+ TILs were associated with nodal metastasis in univariate analyses. Vascular invasion was statistically independent in multivariate analysis. Evidence of neoplastic cells in the vessels and/or at the excision border featured 5 out of 5 metastatic tumors and 13 out of 97 non-metastatic ones. CONCLUSIONS: Completion surgery should be recommended only in pT1 CRC with vascular invasion or with tumor cells reaching the margin. In all other cases, the treatment choice should result from a multidisciplinary discussion on the patient-centered evaluation of the risk-benefit ratio.
BACKGROUND: The population screening campaigns have resulted in increasing the prevalence of endoscopically resected colorectal cancers (CRCs) invading the submucosa (pT1). Synchronous nodal involvement occurs in less than 15 % of these tumors. Histologic criteria currently used for selecting patients needing resection are imprecise and most patients could have been simply followed-up. Tumor infiltrating lymphocytes (TILs) and mismatch repair (MMR) status impact on CRC prognosis. To identify patients requiring completion surgery, the value of histologic variables, TILs and MMR status as risk factors of nodal metastasis was investigated in screening detected and endoscopically removed pT1 CRCs. METHODS: In 102 endoscopically resected pT1 CRCs, the cancer phenotype, CD3+ and CD8+ TILs, and MMR status were assessed. Univariate and multivariate analyses were used to evaluate the correlation with nodal metastasis. RESULTS: Positive resection margin, evidence of vascular invasion and tumor budding, wide area of submucosal invasion, and high number of CD3+ TILs were associated with nodal metastasis in univariate analyses. Vascular invasion was statistically independent in multivariate analysis. Evidence of neoplastic cells in the vessels and/or at the excision border featured 5 out of 5 metastatic tumors and 13 out of 97 non-metastatic ones. CONCLUSIONS: Completion surgery should be recommended only in pT1 CRC with vascular invasion or with tumor cells reaching the margin. In all other cases, the treatment choice should result from a multidisciplinary discussion on the patient-centered evaluation of the risk-benefit ratio.