Unit of Hereditary Digestive Tract Tumours, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian, 1, 20133, Milan, Italy.
Colorectal Surgery Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian, 1, 20133, Milan, Italy.
Int J Clin Oncol. 2020 Sep;25(9):1644-1652. doi: 10.1007/s10147-020-01700-2. Epub 2020 May 19.
Risk factors for metachronous colorectal cancer (mCRC) in Lynch Syndrome (LS) patients are essential for colorectal cancer (CRC) treatment strategy to perform not only a curative but also preventive surgery. The aim of this study was to evaluate the risk factors for mCRC development in LS patients to define the patient subset that may benefit an extended curative and preventive surgical resection.
Patient's clinical history, oncological, molecular and follow-up were collected retrospectively from the Hereditary Digestive Tumors Registry at the National Cancer Institute of Milan. The age-related cumulative risk of mCRC was calculated using the Kaplan-Meier method. Factors significantly associated with mCRC were analyzed with a Cox regression model. Overall and specific competitive risks were also calculated.
In a total of 1346 CRC patients, 159 (11.8%) developed a mCRC after a mean follow-up of 138 months from the primary tumor. The independent risk factors reported by a multivariate analysis were: pathogenetic variants in MLH1 and MSH2 (HR 2.96 and 1.91, respectively) and history of colorectal adenomas (HR 1.54); whereas female sex and extended surgery were protective (HR 0.59 and 0.79, respectively).
Among a high-risk population for CRC, in particular LS, an extended surgery may be considered in CRC patients with specific risk factors (MLH1 or MSH2 germline pathogenic variants, history of colorectal adenomas) to reduce the risk of mCRC development.
林奇综合征（LS）患者发生结直肠多发癌（mCRC）的危险因素对于制定结直肠癌（CRC）治疗策略至关重要，该策略不仅需要进行根治性手术，还需要进行预防性手术。本研究旨在评估 LS 患者发生 mCRC 的危险因素，以确定可能受益于延长根治性和预防性手术切除的患者亚组。
从米兰国家癌症研究所遗传性消化道肿瘤登记处回顾性收集患者的临床病史、肿瘤学、分子生物学和随访资料。采用 Kaplan-Meier 法计算 mCRC 的年龄相关累积风险。采用 Cox 回归模型分析与 mCRC 显著相关的因素。还计算了总风险和特定竞争风险。
在总共 1346 例 CRC 患者中，159 例（11.8%）在原发肿瘤后平均 138 个月的随访中发生 mCRC。多变量分析报告的独立危险因素为：MLH1 和 MSH2 的致病性变异（HR 分别为 2.96 和 1.91）和结直肠腺瘤史（HR 为 1.54）；而女性性别和广泛手术是保护性因素（HR 分别为 0.59 和 0.79）。
在 CRC 高危人群中，特别是 LS 患者中，对于具有特定危险因素（MLH1 或 MSH2 种系致病性变异、结直肠腺瘤史）的 CRC 患者，可考虑进行广泛手术，以降低 mCRC 发生的风险。
