pN3b期胃癌亚分期预后评估的合理性研究

Proposal of a novel subclassification of pN3b for improving the prognostic discrimination ability of gastric cancer patients

目的:第8版TNM分期将pN3b期患者纳入分期,这一变化提高了预后评估准确性。然而鲜有研究评价pN3b期患者的预后情况,并且pN3b期病例涵盖的淋巴结转移范围较广,而如此大范围的淋巴结转移患者纳入到同一分期中,其合理性仍属未知。方法:来自国内多中心的642例pN3b期患者纳入本次研究。采用Kaplan-Meier方法及Cox回归分析计算患者的疾病特异生存并确定预后危险因素。利用限制性立方样条模型评估连续变量与死亡风险比关系。转移淋巴结最佳截断值的判断采用X-tile软件计算。结果:642例pN3b期患者5年疾病特异生存率为15.4%。限制性立方样条模型表明淋巴结转移数目与患者死亡风险比呈非线性关系。利用X-tile软件发现pN3b期患者预后的最佳截断值为24,以此节点将pN3b期患者分为pN3b1期与pN3b2期(pN3b1期:16~24 mLNs,pN3b2期≥25 mLNs),两组病例预后具有显著性差异(P=0.048),并且这一亚分期是pN3b期患者预后的独立危险因素。此外,淋巴结送检数目的增加可提高pN3b1亚分期患者预后,但不能为pN3b2期患者带来生存获益。结论:本研究提出新的分类方法可将pN3b病例分为预后显著差异的2个亚分期,后续研究应当探索这一新分类方法在TNM分期中的意义。

Objective:In the recent edition of the TNMstaging system,pN3b gastric cancer was subclassified for better prognostic accuracy.pN3b is defined as a large range of metastatic lymph nodes(mLNs).However,few studies have evaluated the prognosis of pN3b patients;furthermore,whether these patients were reasonably assigned to the same substage remains unknown.Methods:In total,642 pN3b patients from a multi-institutional cohort in China were included.Disease-specific survival(DSS)was estimated using the Kaplan-Meier method,and independent prognostic factors were identified using Cox proportional hazards regression analysis.A restricted cubic spine model was used to assess the association between continuous variables and logarithm hazard ratios(HRs).The optimal mLN cut-off value for DSS was identified using the X-tile software.Results:The 5-year DSS rate of the total pN3b cohort was 15.4%.Smooth curves showed a non-linear association between mLNs and logarithm HRs.All pN3b gastric cancer patients were assigned into two subclassifications(pN3b1:16-24 mLNs,pN3b2:≥25 mLNs).A significant survival difference was observed between the two subclassifications(P=0.048).Additionally,the examination of more LNs could bring survival benefit only to pN3b1 patients but not to pN3b2 patients.Conclusions:We proposed a novel subclassification that assigned pN3b patients into two subclassifications with significant survival differences.Future studies should explore prognostic value based on this novel subclassification in the TNM staging system.