辅助化疗对高危上尿路尿路上皮癌患者生存预后影响的前瞻性对照观察

Prospective controlled observation ofeffect of adjuvant chemotherapy onsurvival and prognosis ofhigh-risk upper tract urothelial carcinoma patients underwent radical nephroureterectomy

目的探讨根治性肾输尿管切除术(RNU)后辅助化疗对高危上尿路尿路上皮癌(UTUC)患者的生存预后的影响。方法采用前瞻性随机对照研究方法,将2014年1月起收治的接受RNU治疗的高危UTUC患者,按照随机分为两组:化疗组和对照组。其中,化疗组患者于根治术后1个月开始进行3个周期的吉西他滨+顺铂(GC)3周化疗方案,对照组患者则未行术后辅助治疗、进行常规影像学随访。观察化疗临床反应,并对比总结两组患者的总体生存率(OS)、肿瘤特异生存率(CSS)及疾病无进展生存率(PFS),评价辅助化疗(ACT)对UTUC患者的预后影响。结果化疗组患者94例,中位年龄64岁,男37例、女57例,对照组入组患者82例,中位年龄67岁,男31例、女51例。所有化疗患者均未观察到WHO3级及以上肾功能毒性反应。化疗组和对照组的中位随访时间分别为36个月和30个月(P=0.67)。ACT显著改善高危UTUC患者RNU术后OS(P=0.0397,)、CSS(P=0.0255)及PFS(P=0.0033)。分层分析显示:ACT改善淋巴结阳性UTUC患者的预后:中位OS延长9.5个月(P=0.0255)、中位CSS延长11.1个月(P=0.0197)、中位PFS延长20.5个月(P=0.0018);此外,ACT延长T3/4期UTUC患者中位OS 11.6个月(P=0.0183)、中位CSS 16.5个月(P=0.0226)、中位PFS 22.4个月(P=0.0217)。结论ACT是一项安全有效的治疗措施,对RNU术后高危UTUC患者具有显著改善预后的应用价值。

Objective To assess the oncologic outcomes of radical nephroureterectomy(RNU)combined with adjuvant chemotherapy(ACT)in patients with high risk upper tract urothelial carcinoma(UTUC).Methods From January 2014,all high-risk UTUC patients after RNU surgery were enrolled in this prospective comparative trial.And these patients were randomized to ACT group(Gemcitabine+Cisplatin three weeks regimen)and observing group.Cox proportional hazard modeling and Kaplan-Meier analysis were used to determine overall survival(OS),cancer specific survival(CSS)and disease-free survival(PFS)in the cohort.Results The median follow-up duration was36 months(range:6-54)in the ACT group(n=94)and 30 months(range:6-54)in the observing group(n=82).Oncologic outcomes of RNU treated high-risk UTUC patients were improved much significantly by ACT:OS[P=0.0397,HR:1.39(0.91-1.75)],CSS[P=0.0255,HR:1.26(1.07-1.45)]and PFS[P=0.0033,HR:3.78(3.13-4.55)].The further analysis in lymph node positive cohort displayed that median times of oncologic events were prolonged in the ACT group compared with the observing group:OS(26.8mon vs 36.3mon,P=0.0255),CSS(28.2mon vs39.3mon,P=0.0197)and PFS(11.4mon vs 31.9mon,P=0.0018).Additionally in T3/4 cohort,the significant growth in the median times of OS(20.6mon vs 32.2mon,P=0.0183),CSS(21.9mon vs 38.4mon,P=0.0226)and PFS(13.9mon vs 36.3mon,P=0.0217)were observed in ACT group.Conclusion ACT could play the important synergistic role in improving the OS,CSS and PFS of high-risk UTUC patients after RNU.