[Survival analysis of early-onset locally advanced rectal cancer: a retrospective study based on the Surveillance, Epidemiology, and End Results (SEER) database].

Objective: To investigate the factors influencing tumor-specific survival of early-onset locally advanced rectal cancer. Methods: All-age patients with primary locally advanced rectal cancer from the Surveillance, Epidemiology, and End Results (SEER) database (2010 to 2019) were included in this study. Early- and late-onset locally advanced rectal cancer was defined according to age of 50 years at diagnosis. Early-onset locally advanced rectal cancer was divided into five age groups for subgroup analyses. Age, sex, tumor-specific survival time and survival status of patients at diagnosis, pathological grade, TNM stage, perineural invasion, tumor deposits, tumor size, pretreatment CEA , radiotherapy, chemotherapy, and number of lymph node dissections were included. Progression-free survival (PFS) was analyzed and compared between patients with early- and late-onset rectal cancer. Results: A total of 5,048 patients with locally advanced rectal cancer were included in the study (aged 27-70 years): 1,290 (25.55%) patients with early-onset rectal cancer and 3,758 (74.45%) patients with late-onset rectal cancer. Patients with early-onset rectal cancer had a higher rate of perineural invasion (P<0.001), more positive lymph nodes dissected (P<0.001), higher positive lymph node ratios (P<0.001), and a higher proportion receiving preoperative radiotherapy (P=0.002). Patients with early-onset rectal cancer had slightly better short-term survival than those with late-onset rectal cancer (median (IQR ): 54 (33-83) vs 50 (31-79) months, χ2=5.192, P=0.023). Multivariate Cox regression for all patients with locally advanced rectal cancer showed that age (P=0.008), grade of tumor differentiation (P=0.002), pretreatment CEA (P=0.008), perineural invasion (P=0.021), positive number (P=0.004) and positive ratio (P=0.001) of dissected lymph nodes, and sequence of surgery and radiotherapy (P=0.005) influenced PFS. This suggests that the Cox regression results for all patients may not be applicable to patients with early-onset cancer. Cox analysis showed tumor differentiation grade (patients with low differentiation had a higher risk of death, P=0.027), TNM stage (stage III patients had a higher risk of death, P=0.025), T stage (higher risk of death in stage T4, P<0.001), pretreatment CEA (P=0.002), perineural invasion (P<0.001), tumor deposits (P=0.005), number of dissected lymph nodes (patients with removal of 12-20 lymph nodes had a lower risk of death, P<0.001), and positive number of dissected lymph nodes (P<0.001) were independent factors influencing PFS of patients with early-onset locally advanced rectal cancer. Conclusion: Patients with early-onset locally advanced rectal cancer were more likely to have adverse prognostic factors, but an adequate number of lymph node dissections (12-20) resulted in better survival outcomes.目的： 探究影响早发性局部进展期直肠腺癌（LARC）患者肿瘤特异性生存的因素。 方法： 本研究为观察性回顾性研究，遵循《加强流行病学观察性研究报告》（STROBE）报告指南。纳入SEER肿瘤登记数据库中2010年1月1日至2019年12月31日全年龄段原发性LARC患者的临床资料，提取的数据包括患者确诊时的年龄、性别等人口特征；肿瘤病理分级、TNM分期、神经浸润、癌结节、肿瘤直径、术前癌胚抗原（CEA）水平等肿瘤特征；放疗、化疗、淋巴结清扫数等治疗情况；肿瘤特异性生存（CSS）等结局。根据确诊时年龄50岁为界，定义早发和晚发性LARC，并进行组间差异比较，评估多因素Cox回归分析与组间比较共同有统计学意义的变量。进一步对早发性LARC进行多因素Cox回归分析。采用M（Q1，Q3）对非正态分布的连续变量进行描述，两组比较采用Mann-Whitney U检验，多组比较采用Kruskal-Wallis H检验。 结果： 共计纳入5 048例LARC患者，年龄27~70岁，其中早发性LARC患者1 290例（25.55%），晚发性LARC患者3 758例（74.45%）。早发性LARC神经浸润率更高（P<0.001），淋巴结清扫数量和阳性淋巴结数目更多（均P<0.001），接受化疗的比例更高（P<0.001），接受术前放疗的比例更高（P=0.002）。早发性LARC患者CSS优于晚发性直肠癌［54（33，83）个月比50（31，79）个月，χ2=5.192，P=0.023］。对全组LARC患者的Cox回归分析显示，年龄（P=0.008）、肿瘤分化程度（P=0.002）、术前癌胚抗原水平（P=0.008）、周围神经浸润（P=0.021）、清扫淋巴结阳性数（P=0.004）和阳性比率（P=0.001）、手术与放疗顺序（P=0.005）是影响患者CSS的独立因素。对早发性LARC进行的Cox分析结果显示，肿瘤分化程度（低分化患者死亡风险更高，P=0.027）、肿瘤TNM分期（Ⅲ期者死亡风险更高，P=0.025）、T分期（T4期死亡风险更高，P<0.001）、术前CEA（P=0.002）、周围神经浸润（P<0.001）、癌结节（P=0.005）、清扫淋巴结数（清扫12~20枚患者的死亡风险更低，P<0.001）以及淋巴结阳性数目（P<0.001）是早发性LARC患者CSS的独立影响因素。 结论： 早发性LARC患者不良预后因素发生的可能性更高，但充分的淋巴结清扫（12~20枚）会使患者获得更好的生存结局。.