基于SEER数据库的早发性局部进展期直肠腺癌生存分析

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

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-WhitneyU检验,多组比较采用Kruskal-WallisH检验。结果共计纳入5048例LARC患者,年龄27~70岁,其中早发性LARC患者1290例(25.55%),晚发性LARC患者3758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,χ^(2)=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。

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.