人表皮因子受体-2在膀胱尿路上皮癌和上尿路上皮癌中表达的差异性分析

目的 探索人表皮因子受体-2(HER-2)在膀胱尿路上皮癌(UBC)和上尿路上皮癌(UTUC)中表达的差异性,及其与这两种疾病复发及进展的相关性。方法 回顾性分析2015年11月—2022年6月兰州大学第二医院泌尿外科收治的184例尿路上皮癌患者,按照肿瘤部位分为UBC组及UTUC组,比较两组中HER-2的阳性表达率,绘制生存曲线。比较两组患者的无复发生存期(RFS)及无进展生存期(PFS)。应用Cox比例风险模型分析HER-2阳性表达对UBC及UTUC患者复发及进展的影响。结果 UBC患者HER-2阳性表达显著高于UTUC患者(49.6%vs.32.2%,P=0.027)。UTUC患者中,肾盂癌患者HER-2阳性表达相较于输尿管癌差异无统计学意义(30.6%vs.34.8%,P>0.05)。Cox多因素回归分析显示HER-2阳性表达影响UBC复发(P<0.001);HER-2阳性表达(P<0.001)、肿瘤直径≥3 cm(P<0.001)、分期≥T2(P=0.003)以及多发肿瘤灶(P=0.033)均可影响UBC进展;HER-2阳性表达对UTUC复发及进展的影...     

膀胱尿路上皮癌患者外周血CK20、CD105及CD146表达的临床意义

目的检测膀胱尿路上皮癌患者外周血中血清肿瘤标志物CK20、CD105和CD146的表达,探讨CK20、CD105和CD146作为膀胱尿路上皮癌微转移指标的应用价值。方法采用流式细胞仪检测50例膀胱尿路上皮癌患者、30例健康志愿者外周血中CK20及CD105/CD146的表达情况。分析膀胱尿路上皮癌患者外周血中CK20及CD105/CD146的阳性表达率及其与临床病理学指标的关系;CK20及CD105/CD146在膀胱尿路上皮癌患者外周血中表达的相关性及联合检测的意义。结果CK20和CD105/CD146在膀胱癌组中的阳性表达率分别为28.0%和48.0%,其表达与肿瘤分期、病理分级、有无远处转移、肿瘤直径、病灶数量等相关(P<0.05),而与患者性别、年龄无相关性(P>0.05)。患者中有10例同时出现CK20及CD105/CD146阳性表达,两者的表达有相关性(χ2=4.276,r=0.281,P<0.05)。联合检测与单独检测CK20相比,阳性率有所提高,差异有统计学意义(P=0.005);联合检测与单独检测CD105/CD146相比,阳性率差异无统计学意义(P=0.423),但阳性率仍有提高。结论CK20及CD105/CD146对于预测膀胱尿路上皮癌微转移具有较高的敏感性。联合检测CK20及CD105/CD146与单项检测相比,具有更高的敏感性。CK20及CD105/CD146可以作为膀胱尿路上皮癌微转移早期诊断、早期治疗和预后判断的生物学指标。     

联合CK5和CK20免疫染色分析鉴别膀胱癌亚型

目的:探讨联合CK5和CK20的表达与膀胱癌临床病理特征及预后的关系,从而鉴别膀胱癌亚型。方法:收集2012年1月～2018年9月于我院泌尿外科行膀胱癌根治术的患者149例,制备了包含149例膀胱癌组织及62例癌旁组织的组织芯片,采用免疫组化方法检测CK5、CK20及CD44的表达,采用χ~2检验比较各分子的表达与临床病理特征的关系,采用Spearman分析进行分子表达的相关性分析,采用Kaplan-Meier生存分析及多因素Cox回归模型进行预后分析。结果:联合CK5和CK20表达形成CK5~+CK20~+、CK5~+CK20~-、CK5~-CK20~+及CK5~-CK20~-4个亚型;①针对所有膀胱癌患者:149例膀胱癌组织中85例CK5~+(57.0%),82例CK20~+(55.0%)及96例CD44~+(64.4%);62例癌旁组织中56例CK5~+(90.3%),32例CK20~+(51.6%)及36例CD44~+(58.1%);癌与癌旁中CK5表达差异有统计学意义(P0.001),而CK20和CD44差异无统计学意义(分别为P=0.650和P=0.384);CK5与CK20的表达呈负相关(r=-0.294,P0.001),CK5与CD44的表达呈正相关(r=0.488,P0.001);Kaplan-Meier结果表明CK5~-CK20~+亚型的无进展生存期(progression-free survival,PFS)、肿瘤特异性生存期(cancer-specific survival,CSS)、总生存期(overall survival,OS)均差于其他3种亚型;多因素Cox分析结果表明病理分期、淋巴结阳性、CK5~-CK20~+亚型是影响预后的独立危险因素;②针对化疗膀胱癌患者:4个亚型与临床病理特征及预后均无统计学意义。结论:联合CK5与CK20的表达可鉴别膀胱癌亚型,其中CK5~-CK20~+亚型预后最差;亚型与化疗耐药的关系仍需进一步扩大样本进行分析。     

膀胱尿路上皮癌组织中miR-372-5p、CDH1的表达水平及其临床意义

目的:探讨微小RNA-372-5p(miR-372-5p)、E-钙黏蛋白(CDH1)表达与膀胱尿路上皮癌患者预后的关系。方法:选取2014年7月—2015年9月于本院确诊的94例膀胱尿路上皮癌患者肿瘤组织作为膀胱癌组,选取其癌旁正常组织作为对照组。采用实时荧光定量PCR(qRT-PCR)法检测miR-372-5p表达水平,免疫组织化学法检测CDH1蛋白表达,Ualcan数据库检索CDH1在膀胱尿路上皮癌中的表达;Kaplan-Meier法分析膀胱尿路上皮癌患者肿瘤组织miR-372-5p、CDH1表达与预后的关系;多因素Cox回归分析影响膀胱尿路上皮癌患者预后的因素。结果:Ualcan数据库中,膀胱尿路上皮癌肿瘤组织中CDH1水平高于正常膀胱组织(P0.05)。膀胱癌组miR-372-5p表达水平低于对照组,CDH1阳性表达率高于对照组(P0.05)。肿瘤大小3 cm、可见肌层浸润、组织学分级3级膀胱尿路上皮癌患者miR-372-5p低表达、CDH1阳性表达比例高于肿瘤大小≤3 cm、未见肌层浸润、组织学分级1、2级患者(P0.05)。miR-372-5p高表达膀胱尿路上皮癌患者5年生存率高于miR-372-5p低表达患者(88.89%vs. 67.35%,χ~2=6.274,P0.05);CDH1阳性表达膀胱尿路上皮癌患者5年生存率低于CDH1阴性表达患者(70.00%vs. 91.18%,χ~2=5.609,P0.05)。CDH1是影响膀胱尿路上皮癌患者预后死亡的独立危险因素(P0.05),miR-372-5p是影响膀胱尿路上皮癌患者预后死亡的保护因素(P0.05)。结论:膀胱尿路上皮癌患者肿瘤组织中miR-372-5p表达下调、CDH1表达上调,二者均与临床病理特征相关,且是患者预后的影响因素。     

基于TCGA数据库筛选膀胱尿路上皮癌预后分子标签

目的通过对癌症基因组图片(TCGA)数据库中转录组数据进行分析,筛选与膀胱尿路上皮癌相关的预后分子标签。方法提取TCGA数据库中膀胱尿路上皮癌患者的临床数据以及膀胱尿路上皮癌和癌旁组织中的转录组数据,采用LASSO-Cox回归分析筛选膀胱尿路上皮癌预后相关的mRNA,并构建膀胱尿路上皮癌的预后分子标签。结果首先筛选出膀胱尿路上皮癌和膀胱正常组织中差异表达基因8738个,经过单因素Cox分析得到2824个与膀胱尿路上皮癌预后相关的基因(P<0.05),选取P<0.0001的mRNA 225个,进一步采用LASSO-Cox回归分析筛选出11个与膀胱尿路上皮癌预后相关的基因,分别为TPSTI.ANXAl、LINC01138、AMIG02.,H00KI、AC005730.2、KANK4.,PEX5L、AL353572.1、CATSPER4、AL645939.1,最后联合这11个基因构建出膀胱尿路上皮癌的预后分子标签。利用分子标签基因构建的模型能将膀胱尿路上皮癌划分为高表达组和低表达组,绘制分子标签生存曲线及受试者工作特征(R0C)曲线,结果显示:分子标签表达水平与膀胱尿路上皮癌患者的预后有显著性关联,分子标签值越高,患者预后越差。结论通过对TCGA数据库的分析,发现TPSTI、ANXAI JLINC01138、AMI-G02、H0OK1、AC005730.2、KANK4、PEX5L、AL353572.1、CATSPER4、AL645939.1和AL645939.1对膀胱尿路上皮癌的预后有影响,且构建的分子标签表达水平与膀胱尿路上皮癌的预后有显著性关联。     

多发性上尿路上皮癌的临床病理特点及预后分析

目的:探讨多发性上尿路上皮癌(UTUC)的临床和病理特点及预后。方法:回顾性分析230例UTUC患者的临床和病理资料,比较多发性UTUC与单发性UTUC组间的病理TN分期、Grade分级、合并膀胱内肿瘤有无差异(χ2检验)以及两组间术后生存时间是否相同(生存分析采用Kaplan-Meier生存曲线及Wilcoxon检验)。结果:38例患者术后病理诊断为多发性UTUC,与单发性UTUC相比,其预示着更高的病理分级(P=0.031)、分期(P<0.01)、淋巴结转移率(P=0.023)及合并膀胱肿瘤的比例(P=0.002)。术后随访3～302个月,平均随访30个月,发现死亡66例,其中多发性UTUC组死亡13例,术后3年总体生存率为40.0%(P=0.036)。结论:多发性UTUC具有更强的生物学侵袭特性,预后更差,治疗策略应选择根治性肾输尿管切除术,术后需要更严密随访。     

上尿路尿路上皮癌术后复发膀胱癌分子机制的研究进展

上尿路尿路上皮癌(UTUC)是一种罕见的恶性肿瘤, 约占尿路上皮癌的5%。肾输尿管根治性切除术(RNU)是UTUC治疗的金标准, 但术后膀胱癌的复发率可高达20%以上。UTUC在术后管理中最具挑战性的是准确预测肿瘤复发和疾病进展。了解UTUC术后复发膀胱癌的分子机制对指导肿瘤治疗及评估患者预后十分重要, 现就相关研究进展进行综述。     

术前全身免疫炎症指数评价上尿路上皮癌患者术后膀胱复发风险的价值

目的探讨术前全身免疫炎症指数(SII)对上尿路上皮癌(UTUC)根治术后膀胱复发的预测价值。方法收集宁夏医科大学总医院泌尿外科收治的110例UTUC患者临床资料。采用ROC曲线确定SII预测膀胱内复发风险的截断值,比较不同SII患者的临床病理资料及无复发生存期(RFS)。采用Cox比例风险回归分析影响UTUC术后膀胱复发的影响因素。结果ROC曲线显示,SII对UTUC患者RFS评价的曲线下面积为0.688,最佳截断值为410.3×10⁹。肿瘤T分期、淋巴结转移是影响UTUC患者SII的主要危险因素(P<0.05)。SII<410.3×10⁹组与SII≥410.3×10⁹组的膀胱内复发率分别为10.5%、41.5%,Kaplan-Meier生存曲线显示,SII≥410.3×10⁹组患者RFS显著差于SII<410.3×10⁹组(P=0.000)。Cox比例风险回归显示术前肾积水、术前SII是影响UTUC患者术后膀胱复发的独立危险因素。结论术前SII作为一种炎症指标,可用于评价UTUC根治术后膀胱内复发的风险。     

淋巴细胞与单核细胞比值在上尿路尿路上皮癌根治术后患者预后评估中的价值

目的探讨在上尿路尿路上皮癌(UTUC)根治术后的患者中,术前外周血淋巴细胞与单核细胞比值(LMR)对其预后的预测价值。方法回顾性分析2011-10-2015-12间郑州大学第一附属医院接受根治性手术的UTUC患者146例的临床资料。根据截至查找器选取最佳截止点。采用卡普兰-梅尔法和对数秩检验绘制生存曲线。使用比例风险回归模型进行多因素分析。结果在146例患者中,淋巴细胞与单核细胞比值的最佳截止点为2.195。以此将患者分为低水平组和高水平组。LMR水平与病理肿瘤分期显著相关(P0.05)。高水平组及低水平组患者5年总生存率分别为(81.8±7.8%)和(27.7±26.9%),5年肿瘤特异生存率分别为(83.5±7.6%)和(28.6±26.9%),差异均有统计学意义(P0.001)。单因素分析显示低LMR水平与OS和CSS率下降显著相关(P0.001)。多因素分析显示多灶、病理T分期、LMR水平是UTUC预后OS的独立预测因素(P0.05)。结论 LMR可作为UTUC患者生存结局的一个独立预测因子。可能成为一种有用的生物标志物。     

年轻上尿路尿路上皮癌患者的临床病理和预后特征

目的探讨年轻(55岁)上尿路尿路上皮癌(UTUC)患者的临床病理特点,为UTUC的个性化治疗提供更多的临床依据。方法回顾性分析1999年到2011年期间经术后病理确诊并且随访资料完整的UTUC患者687例,根据年龄是否小于55岁将其分为年轻组(55岁)和年长组(≥55岁),对比两组患者的临床病理资料;结果年轻上尿路上皮癌男性患者较多(P=0.023),多具有吸烟史(P=0.003),较少伴肿瘤坏死(P=0.014),合并中度或重度肾功能不全(肾小球率过滤估算值eGFR60mL/min/1.73m2)的比例较低(P0.001),VIM基因启动子甲基化率较低(P=0.035);肾积水与年轻UTUC的病理高级别[(G1+G2)vs.G3]相关(P=0.002);年龄55岁的男性UTUC患者术后生存情况比≥55岁的男性患者好;吸烟(P=0.045)、肿瘤的多灶性(P=0.049)和最大径5cm(P=0.007)是55岁患者的术后生存的独立危险因素。结论年龄55岁的年轻UTUC患者在性别、生活习惯、肾功能、基因启动子甲基化和病理特点等方面存在较大差异,临床医生可参考吸烟史、肿瘤的多灶性和最大径来评估其预后。     

细胞角蛋白7、18、19在壶腹周围癌淋巴结微转移灶的检测及临床意义

目的探讨细胞角蛋白对壶腹周围癌淋巴结微转移的检出率,并分析淋巴结微转移与临床预后的关系,为提高临床综合疗效提供理论依据。方法应用细胞角蛋白(CK7、CK18、CK19)单克隆抗体,对45例壶腹周围癌根治术后经病理常规HE染色阴性的186枚淋巴结进行免疫组织化学技术(S P法)检测,结合随访资料进行临床预后分析。结果45例壶腹周围癌根治术后HE染色阴性的186枚周围淋巴结中,有9例(20%、9/45)34枚(18.3%、34/186)淋巴结中检出微小转移灶。免疫组化诊断微转移阳性组和阴性组的1年复发率分别是88.9%(8/9)和16.7%(6/36),两组间有显著性差异(P<0.05)。不同单克隆抗体(CK7、CK18、CK19)检测发现,CK19在壶腹周围癌186枚淋巴结的检出率高达15.6%(29/186),CK19与壶腹周围癌淋巴结微转移关系密切(P<0.05)。结论对常规病理检查阴性的壶腹周围癌淋巴结进行CK7、CK18、CK19检测有助于发现微转移灶,为提高淋巴结微转移诊断的准确性、判断临床分期、估计预后及选择辅助治疗提供理论依据。CK系列单抗联合检测可提高淋巴结微转移阳性检出率。     

Decreased expression of KAI1 metastasis suppressor gene is a recurrence predictor in primary pTa and pT1 urothelial bladder carcinoma

OBJECTIVE: To examine the expression of the KAI1 metastasis suppressor gene and to evaluate its relationship with tumor recurrence in primary pTa and pT1 urothelial bladder carcinoma. METHODS: Samples were obtained from 87 patients after transurethral resection (TUR). Tumor stage and grade were reviewed in 33 patients with pTa and in 54 patients with pT1, with a mean follow-up time of 47.4 +/- 30.1 months. The KAI1 protein immunohistochemical assay was performed. Prognosis was analyzed using the Kaplan-Meier method and Cox's proportional hazards model. Correlation between KAI1 expression and recurrence according to each clinicopathological factor was comparatively evaluated using the chi-squared test. RESULTS: Decreased expression of KAI1 protein failed to reach statistical significance for stage (P = 0.25) or morphology of tumor stem (P = 0.19), but it was significantly related to tumor size (P = 0.016). The recurrence-free 5-year survival rates of the group with decreased KAI1 expression was 69.7%, which was significantly higher than the 22.2% for the KAI1-positive group (P < 0.0001). In univariate and multivariate analyses, decreased expression of KAI1 protein, stage pT1, tumor size >3 cm and sessile tumors were independent prognosis factors of recurrence. Despite the lower recurrence rate expected by considering only the clinicopathological factors, decreased KAI1 expression was able to identify the group with a high risk of recurrence. CONCLUSIONS: Downregulated KAI1 expression in bladder tumors tends to relate to stage and morphology of the tumor stem and was significantly correlated to tumor size. Decreased expression of KAI1 was associated with the degree of invasiveness and progression of the cancer and was an independent prognostic factor of recurrence in primary pTa and pT1 urothelial bladder carcinoma.     

Overexpression of Eg5 predicts unfavorable prognosis in non‐muscle invasive bladder urothelial carcinoma

Objective: To investigate the relationship between Eg5 expression and prognosis of patients with non‐muscle invasive bladder urothelial carcinoma. Methods: Eg5 expression was examined by immunohistochemistry in non‐muscle invasive urothelial carcinoma specimens (grade: G1, 32 cases; G2, 92 cases; and G3, 39 cases. Stage: pTa, 49 cases and pT1, 114 cases). The correlation between clinicopathological characteristics and Eg5 expression was evaluated. The prognostic significance of Eg5 immunoreactivity was analyzed through survival analysis in 163 non‐muscle invasive cases that were treated with transurethral resection and adjuvant intravesical instillations. Results: The expression of Eg5 was significantly associated with tumor grade (P = 0.006), with a trend towards significant association with stage (P = 0.057). The 163 patients with non‐muscle invasive tumors were regularly followed with the mean of 32.52 (from 6 to 72) months. Univariate analysis showed Eg5 overexpression exhibited a significant unfavorable influence on intravesical recurrence (P = 0.012) while having only a marginal correlation with disease progression (P = 0.070). Subsequent Cox hazard multivariate analysis showed that both grade (P = 0.045) and Eg5 expression (P = 0.029) were independent predictors for early intravesical recurrence. Conclusions: Overexpression of Eg5 correlates with poor differentiation of bladder cancer, and it represents an independent prognostic factor in predicting early intravesical recurrence in non‐muscle invasive bladder carcinoma patients.     

膀胱癌CK20及Ki-67的表达及相关性

目的 探讨角蛋白20(CK20)和Ki-67在膀胱癌中的表达与膀胱癌的侵袭、转移及预后的关系.方法 用免疫组织化学SP法检测154例膀胱癌组织中CK20和Ki-67的表达.结果 CK20在103例肿瘤组织中有表达,阳性率为66.9%.CK20的表达和膀胱癌的T分期及远处转移呈正相关(P<0.05).Ki-67在126例肿瘤组织中有阳性表达,阳性率为81.8%.Ki-67在膀胱癌组织的表达与肿瘤病理分级、T分期、远处转移呈正相关(P<0.05).Spearman等级相关分析表明两者明显相关(P<0.05).结论 CK20及Ki-67可能参与了膀胱癌的侵袭与转移,CK20与Ki-67可作为预后判断因子,结合病理分级和临床分期分析能提高对膀胱癌患者预后判断的准确性.     

Peripelvic/periureteral fat invasion is independently associated with worse prognosis in pT3 upper tract urothelial carcinoma

Purpose

To elucidate the reasons for conflicting results regarding the prognostic significance of tumor location in upper tract urothelial carcinoma (UTUC), we analyzed the stage-specific impact of tumor location on oncological outcomes following radical nephroureterectomy (RNU).

Methods

Data from 392 patients who underwent RNU with curative intent between 1991 and 2010 were reviewed. Prognostic impact of tumor location and various clinicopathological factors for recurrence-free survival (RFS) and cancer-specific survival (CSS) was evaluated using Kaplan–Meier and Cox regression analyses at each pathological stage. Tumor location was classified as renal pelvis or ureter, and pT3 tumors were further stratified as invading the renal parenchyma or peripelvic or periureteral fat.

Results

In stage-specific analysis, tumor location did not have prognostic significance in patients with ≤pT2 tumors, whereas RFS and CSS rates were significantly lower in patients with pT3 ureteral tumors than renal pelvic tumors. Subgroup analysis showed that RFS and CSS rates were significantly higher for pT3 tumors invading the renal parenchyma than the peripelvic or periureteral fat. On multivariate analysis in pT3 tumors adjusting other clinicopathological parameters, tumor location remained significant predictors for both RFS and CSS. Compared with tumors invading renal parenchyma, tumors invading peripelvic fat or periureteral fat were associated with about 3.5 times higher risk for cancer-specific mortality (p < 0.05).

Conclusions

Location-dependent survival difference exists only in patients with pT3 UTUC. Conflicting institutional results regarding tumor location in UTUC may be due to difference in the proportions of parenchymal versus peripelvic fat invasion in pT3 pelvic tumors.     

膀胱癌CK20及Ki-67的表达及相关性

目的 探讨角蛋白20(CK20)和Ki-67在膀胱癌中的表达与膀胱癌的侵袭、转移及预后的关系.方法 用免疫组织化学SP法检测154例膀胱癌组织中CK20和Ki-67的表达.结果 CK20在103例肿瘤组织中有表达,阳性率为66.9%.CK20的表达和膀胱癌的T分期及远处转移呈正相关(P<0.05).Ki-67在126例肿瘤组织中有阳性表达,阳性率为81.8%.Ki-67在膀胱癌组织的表达与肿瘤病理分级、T分期、远处转移呈正相关(P<0.05).Spearman等级相关分析表明两者明显相关(P<0.05).结论 CK20及Ki-67可能参与了膀胱癌的侵袭与转移,CK20与Ki-67可作为预后判断因子,结合病理分级和临床分期分析能提高对膀胱癌患者预后判断的准确性.     

Combination of CK20 and Ki-67 Immunostaining Analysis Predicts Recurrence,Progression, and Cancer-Specific Survival in pT1 Urothelial Bladder Cancer

Background

The prognostic value of CK20, Ki-67, and p53 has been investigated for non–muscle-invasive urothelial bladder cancers but not for the distinct and clinically challenging subset of pT1 bladder cancers.

Objective

To evaluate the prognostic value of CK20, Ki-67, and p53 within the largest series of pT1 urothelial bladder cancers.

Design, setting, and participants

Data from 309 patients with pT1 urothelial bladder cancer from one single urologic centre were collected.

Intervention

Adjuvant instillation of bacillus Calmette-Guérin was performed in each patient. A second resection was performed after 4–8 wk. A total of 76 patients underwent cystectomy.

Outcome measurements and statistical analysis

We conducted histomorphologic analysis; immunohistochemistry for CK20, Ki-67, and p53; and univariate and multivariate Cox regression models including recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS).

Results and limitations

At a median follow-up of 49 mo, we found recurrence and progression and disease-specific mortality rates of 22.7%, 20.1%, and 15.9%, respectively. CK20 expression was significantly correlated with RFS in multivariate analysis (hazard ratio [HR]: 5.89; 95% confidence interval [CI], 1.44–24.15; p = 0.014). In multivariate analysis, Ki-67 was the only marker significantly correlated with PFS (HR: 2.80; 95% CI, 1.45–5.43, p = 0.002). Ki-67 (HR: 3.83; 95% CI, 1.59–9.26; p = 0.003), and CK20 (HR: 8.44; 95% CI,1.16–61.34; p = 0.035) were significantly correlated with CSS in multivariate analysis. The combination of CK20 and Ki-67 showed significantly worse RFS (p = 0.026), PFS (p = 0.003), and CSS (p < 0.001) in tumours with a high proliferation index and abnormal CK20 expression. A retrospective study design was the major limitation of this study.

Conclusions

Our present analysis of the largest series of patients with pT1 urothelial bladder cancer published to date found Ki-67 and CK20 to be potential prognostic markers improving the risk stratification of pT1 bladder tumours. They are reliable indicators of biologic aggressiveness and may contribute to decision making on therapeutic strategy for pT1 bladder carcinomas.     

Upper urinary tract urothelial carcinoma with loco-regional nodal metastases: insights from the Upper Tract Urothelial Carcinoma Collaboration

Study Type – Therapy (multi‐insititutional cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Neoadjuvant chemotherapy offers survival benefits for patients with urothelial carcinoma of the bladder. However, it is still underutilized in the ‘biologically similar’ upper tract urothelial carcinoma. Systemic chemotherapy in a neoadjuvant setting is a more attractive option, as loss of renal function after nephrectomy can complicate the administration of adjuvant chemotherapy. We found that preoperative systemic therapy followed by aggressive surgical debulking is a promising treatment strategy for upper tract urothelial carcinoma patients with known or at risk of loco‐regional nodal metastasis.

OBJECTIVE

? To describe a multicentre experience with preoperative platinum‐based chemotherapy before radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) with loco‐regional nodal metastases.

PATIENTS AND METHODS

? We identified 313 patients from the UTUC Collaboration (over 1200 patients), who underwent RNU with concomitant retroperitoneal lymph node dissection between 1990 and 2007 and met the inclusion criteria for one of three groups. ? Group 1 comprised patients who received chemotherapy before RNU because of biopsy‐proven loco‐regional nodal metastases. ? Group 2 consisted of patients who underwent primary RNU and were found to have metastatic nodal disease on final pathological review (node‐positive). ? Group 3 comprised a comparative cohort of patients treated with primary RNU for invasive or locally advanced (pT2/pT4) node‐negative (N0) UTUC.

RESULTS

? Groups 1, 2 and 3 included 18, 120 and 175 patients, respectively. The 5‐year disease‐free survival rates were 49%, 30% and 64%, whereas the 5‐year cancer‐specific survival rates were 44%, 36% and 69% in groups 1, 2 and 3, respectively. ? In group 1, on final pathological evaluation, nine patients were pN0, six patients were pT0 and five patients had pT0N0 disease. Kaplan–Meier survival analyses showed similar recurrence and survival rates in group 1 compared with group 3 (P= 0.14 and P= 0.06, respectively). ? Meanwhile, group 2 had significantly lower disease‐free and cancer‐specific survival rates compared with group 3 (P < 0.001 and P < 0.001, respectively) and compared with group 1 (P= 0.04 and P= 0.06, respectively).

CONCLUSIONS

? Preoperative chemotherapy followed by aggressive surgical consolidation may yield favourable oncological outcomes in patients with UTUC with loco‐regional nodal metastases. ? These data support further evaluation of neoadjuvant systemic therapy in patients at risk for locally advanced UTUC.     

The Role of Systemic Chemotherapy in Management of Upper Tract Urothelial Cancer

Upper tract urothelial cancer (UTUC) accounts for roughly 5 % of all urothelial cancers. At presentation, 30 % of patients demonstrate invasive and/or locally advanced disease, 30–40 % have regional lymph node involvement, and 20 % harbor metastatic disease. Systemic recurrence and progression rates after surgery for patients with advanced disease range between 45–60 %. Five-year cancer specific survival rates for pT2 and pT3 tumors are 73 % and 40 %, respectively. Median survival for patients with pT4 disease is approximately 6 months. Nonetheless, there is a lack of improvement in the rates of systemic recurrence and progression in patients with advanced UTUC. Extrapolating evidence obtained from experience with multi-modal therapy of patients with urothelial bladder cancer, additional improvements in oncological outcomes for patients with UTUC can be achieved through integration of effective systemic chemotherapy with local tumor control. We provide an overview of the rationale and utilization strategies of peri-operative systemic chemotherapy in patients with UTUC.