Objective: To investigate the correlation between the neoadjuvant rectal (NAR) score and long-term survival in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy. Methods: Clinical and pathological data of 487 patients diagnosed with rectal adenocarcinoma from October 2004 to April 2014 at Sun Yat-sen University Cancer Center who had received neoadjuvant chemoradiotherapy were retrospectively analyzed and the impact of NAR score on prognosis studied. Disease-free-survival (DFS) was calculated by the Kaplan-Meier method and survivals compared using the log-rank test. Cox models were used for univariate and multivariate analyses. Receiver operating characteristic curves were utilized to evaluate the predictive capability of NAR and tumor regression grade scores for the risk of 10-year postoperative recurrence and metastasis. The Delong test was employed to compare the diagnostic performance of the two scores. Results: Of the 487 patients included in the study, 166 were men (34.1%). The median age was 56 years (interquartile range [IQR]: 46-63). All patients completed adequate preoperative chemoradiotherapy and underwent R0 resection.The median interval between the end of chemoradiotherapy and surgery was 51 days (IQR: 44-58). Post-chemoradiotherapy downstaging occurred in 329 patients (67.6%). Tumor regression grades (TRGs) were 1-2 in 246 patients (50.5%) and 3-4 in 241 patients (49.5%). A total of 394 patients (80.9%) received postoperative chemotherapy. NAR scores were <8 in 182 patients (37.4%), 8-16 in 180 (37.0%), and >16 in 125 (25.6%). The median follow-up time was 111.5 months (IQR: 70.7-133.7 months). One hundred and thirteen patients died of rectal cancer, among whom 13 patients developed local recurrence, 88 patients developed distant metastasis, and 12 patients had unknown recurrence patterns. The 10-year DFS and overall survival rate of f the whole group were 68.9% and 71.5% respectively. The 10-year DFS rates for patients with NAR scores <8, 8-16, and >16 were 85.1%, 80.5%, and 66.4%, respectively (P<0.001). Multivariate analyses revealed that the Dixon operation (HR=0.606, 95%CI: 0.408-0.902, P=0.014), and >16 (HR=2.569, 95%CI: 1.559-4.233, P<0.001) were independent predictors of the 10-year DFS of patients with locally advanced rectal cancer (P<0.05 for all). In the entire patient cohort, the AUC of the receiver operating characteristic curve for NAR score predicting 10-year recurrence and metastasis was 0.67 (95%CI: 0.62-0.72), whereas the AUC for TRG score was 0.54 (95%CI: 0.49-0.60). The two scores differed significantly in accuracy (Z=-4.06, P<0.001), the NAR score being a significantly better predictor of risk of 10-year recurrence and metastasis than the TRG score. Conclusion: The NAR score is a reliable predictor of 10-year DFS in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy followed by curative surgery.
目的: 探究新辅助直肠(NAR)评分对接受新辅助放化疗联合根治性手术的局部进展期直肠癌患者长期生存的预测能力。 方法: 采用回顾性队列研究方法。回顾性分析中山大学肿瘤防治中心2004年10月至2014年4月期间病理确诊为直肠腺癌而接受新辅助放化疗和根治性手术的局部进展期直肠癌患者的临床病理资料和10年以上的随访资料,排除存在除直肠以外的其他脏器原发性肿瘤、术前伴发远处转移和无法获取随访数据者。比较NAR评分高低对本组患者预后的影响。应用Kaplan-Meier法计算无病生存期(DFS),使用Log-rank法比较生存差异,使用Cox模型进行DFS的单因素和多因素分析;利用受试者工作特征曲线(ROC)进行NAR和肿瘤退缩分级(TRG)评分对患者术后10年复发转移结局的预测能力进行评估,并使用Delong检验比较两种评分的检验效能。 结果: 487例患者中,男性166例(34.1%);中位年龄为56(46,63)岁。所有患者均完成了术前足量放化疗,并由外科医生评估能够进行手术后,进行了肿瘤的R0切除;手术距离放化疗结束中位间隔时间为51(44,58)d。术前放化疗后降期329例(67.6%),TRG1~2级为246例(50.5%),TRG3~4级为241例(49.5%)。394例患者(80.9%)接受了术后化疗。全组NAR评分<8分有182例(37.4%),8~16分有180例(37.0%),>16分有125例(25.6%)。全组中位随访时间为111.5(70.7,133.7)个月,113例患者死于直肠癌,其中13例患者出现局部复发,88例患者出现远处转移,12例复发转移模式未明。全组10年DFS以及总体生存率分别为68.9%和71.5%。生存分析显示:NAR评分<8分、8~16分和>16分者10年的DFS率分别为85.1%、80.5%和66.4%,差异有统计学意义(P<0.001)。Cox多因素分析显示:术式为Dixon术(HR=0.606,95%CI:0.408~0.902,P=0.014)和NAR评分>16分(HR=2.569,95%CI:1.559~4.233,P<0.001)均是影响局部进展期直肠癌患者10年DFS的独立预后因素(均P<0.05)。在全组患者中,NAR评分预测10年复发转移结局的ROC曲线的曲线下面积(AUC值)为0.67(95%CI:0.62~0.72),TRG评分预测10年复发转移结局的ROC曲线AUC值为0.54(95%CI:0.49~0.60),两者比较差异具有统计学意义(Z=-4.06,P<0.001)。 结论: NAR评分对接受了新辅助放化疗联合根治性手术的局部进展期直肠癌患者的10年DFS具有良好的预测作用,且预测效能显著高于TRG评分。.