目的 统计分析T1 G3膀胱尿路上皮癌复发、进展、死亡的预后风险因素,尝试制订相对客观准确的预后评估模型.方法 收集1998年1月至2006年10月诊断为T1 G3膀胱尿路上皮癌患者187例,回顾患者临床资料,进行临床流行病学调查并随访患者预后情况.187例患者的石蜡标本分别进行p53、成纤维细胞生长因子受体3(FGFR3)、E-钙黏素、CD-34标记的微血管密度(MVD)、增殖细胞核抗原(Ki-67)免疫组化染色,分析其表达情况.寿命表法估算本组患者复发、进展及死亡各时点的累积概率.纳入年龄、性别、出现症状到就诊时间、肾积水、手术方式、术后即刻灌药、膀胱灌注药物种类、肿瘤最大径、肿瘤数量、肿瘤形态、原位癌、复发次数、初次复发时间≤6个月、p53、FGFR3、E-钙黏素、MVD计数、Ki-67共18个因素作为拟评估的预后风险因素,分别进行肿瘤复发、疾病进展、死亡的Kaplan-Meier单因素及Cox多因素生存分析.得到T1 G3膀胱尿路上皮癌预后最佳比例风险模型后,以各预后因素的偏回归系数作为风险积分权重,计算得到T1 G3膀胱尿路上皮癌复发、进展的预后评估积分系统.结果 本组患者随访12 ～111个月(中位随访时间39个月).随访期内肿瘤复发100例(53.5％),进展61例(32.6％),死亡37例(19.8％).本组患者1、2、3、5年肿瘤复发率分别为35.0％、60.0％、63.0％、65.0％；1、2、3、5年疾病进展率分别为12.0％、27.0％、34.0％、38.0％；1、2、3、5年死亡率分别为0、11.0％、17.0％、26.0％.肿瘤最大径、肿瘤数量、即刻灌注、初次复发时间≤6个月、p53、FGFR3是T1 G3膀胱尿路上皮癌复发的危险因素,计算患者复发风险总积分并分为-3 ～6、7～19、20～32三组,其1年复发率分别为3％、35％、81％,5年复发率分别为20％、65％、100％.肿瘤形态、原位癌、初次复发时间≤6个月、复发次数、p53、E-钙黏素是T1 G3膀胱尿路上皮癌进展的危险因素,计算患者疾病进展风险总积分并分为6 ～ 14、15 ～ 23、24～30三组,其1年进展概率分别为2％、19％、56％,2年进展概率分别为7％、33％、88％.肿瘤进展是患者死亡的危险因素(RR= 324.70,95％ CI:9.848 ～ 10707.800).结论 根据T1 G3膀胱尿路上皮癌肿瘤复发、疾病进展的各项风险因素定量计算各因素对预后的影响,为T1G3膀胱尿路上皮癌预后评估模型的建立做了初步尝试,有利于为T1G3膀胱尿路上皮癌患者的个体化治疗提供决策依据.%Objective To formulate the systems of prognostic evaluation that allowed urologists to easily calculate a T1 G3 bladder cancer patient's short-and long-term risk score of recurrence,progression and death after transurethral resection.Methods The 187 cases with T1 G3 bladder cancer were diagnosed from January 1998 to October 2006.Clinical epidemiology study was carried out and prognosis information were collected.The expression of p53,fibroblast growth factor receptor 3 (FGFR3),E-cadherin,Ki-67 and microvesseldensity (MVD) of all patients' samples were detected using immunohistochemistry.The 18 prognostic risk factors were planed to estimate including gender,age,the time from symptom emerging to visiting doctor,hydronephrosis,operation ways,immediately intravesical instillation,drug of intravesical instillation,tumor size,number of tumors,tumor modality,cancer in situ,the first recurrence time ≤ 6 months,frequency of recurrence,p53,FGFR3,E-cadherin,Ki-67 and MVD.The risk factors were preliminary screened with Kaplan-Meier univariate analysis and then determined finally with multivariate Cox proportional hazards regression model.Based on the coefficients of the variables in the multivariate model,a weight for each level of each variable was obtained and the prognostic evaluation score of T1 G3 bladder cancer was calculated.Results Based on an average follow-up of 46 months,100 cases of T1G3 bladder cancer recurred (53.5％),61 cases progressed (32.6％) and 37 cases died (19.8％).The 1-,2-,3-,5-year probability of tumor recurrence was 35.0％,60.0％,63.0％,65.0％.The 1-,2-,3-,5-year probability of disease progression was 12.0％,27.0％,34.0％,38.0％ and the 1-,2-,3-,5-year probability of death was 0,11.0％,17.0％,26.0％ respectively.The tumor size,number of tumors,immediately intravesical instillation,the first recurrence time≤ 6 months,p53 and FGFR3 were the risk factors of the tumor recurrence of T1 G3 bladder cancer.The total recurrence risk score of each patient was calculated.According the recurrence risk score,the patients were divided into-3-6 group,7-19 group and 20-32 group.The 1-year probability of tumor recurrence was 3％,35％,81％ in each group and the 5-year probability of tumor recurrence was 20％,65％,100％.The tumor modality,cancer in situ,the first recurrence time≤6 months,frequency of recurrence,p53 and E-cadherin were the risk factors of the disease progression.The total progression risk score of each patient was calculated.According the progression risk score,the patients were divided into 6-14 group,15-23 group and 24-30 group.The 1-year probability of progression was 2％,19％,56％ in each group and the 2-year probability was 7％,33％,88％.Only progression was the risk factor of death(RR = 324.70,95％ CI:9.848-10707.800).Conclusions Based on the risk coefficient was translated into prognostic score and the tables of prognostic evaluation of T1G3 bladder cancer was founded initially,which showed the influence of each risk factor with intuitional scores.The model of prognostic evaluation of T1 G3 bladder cancer could help the urologist to make decisions conveniently.
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