上尿路尿路上皮癌患者膀胱复发灶的危险因素分析

Muscle-invasive upper tract urothelial carcinoma predicts invasive bladder recurrence tumor

目的探讨上尿路尿路上皮癌（UTUC）患者膀胱复发灶出现肌层浸润、高级别和膀胱多次复发的危险因素，并分析影响其预后的危险因素。 方法回顾性分析2000年1月至2013年12月我院确诊为UTUC且行根治性肾输尿管切除术后出现膀胱复发的148患者的临床资料。男69例（46.6%），女79例（53.4%）。年龄34～82岁，中位年龄67岁。83例（56.1%）有肾积水，68例（45.9%）肿瘤直径〉3 cm，80例（54.1%）最大肿瘤位于肾盂，32例（21.6%）有吸烟史。采用logistic回归分析膀胱复发灶出现肌层浸润、高级别和膀胱多次复发的危险因素，采用Kaplan-Meier曲线对UTUC膀胱复发情况做单因素分析，并行log-rank检验，对单因素分析结果提示的危险因素再行Cox回归分析。 结果本组148例中，非肌层浸润性UTUC（Tis、Ta和T1） 51例（34.5%），肌层浸润性UTUC（T2～T4） 97例（65.5%）；膀胱复发灶中非肌层浸润性（Tis、Ta和T1）患者119例（80.4%），肌层浸润性（T2～T4）患者29例（19.6%）；原发UTUC和膀胱复发灶中高级别肿瘤（G3）分别为41例（27.7%）和53例（35.8%）。膀胱复发1次者94例（43.5%），多次（≥2次）者54例（36.5%）。148例随访时间为8～142个月，中位时间59.5个月，48例（32.4%）死于UTUC，中位死亡时间为41.5个月（8～115个月）。单因素logistic分析结果显示，膀胱复发灶肿瘤高级别与原发UTUC肌层浸润（P＝0.002）、肿瘤高级别（P＝0.046）和肿瘤形态（P＝0.034）相关；膀胱复发灶肌层浸润与原发UTUC肌层浸润相关（P＝0.009）；膀胱多次复发与性别相关（P＝0.007）。多因素logistic回归分析结果显示原发UTUC肌层浸润是膀胱复发灶肿瘤高级别（HR＝3.948，95%CI 1.589～9.813, P＝0.004）和肌层浸润（HR＝5.512，95%CI 1.654～18.37, P＝0.004）的危险因素，且女性更容易发生多次膀胱复发。单因素和多因素Cox回归分析结果显示，仅原发UTUC肌层浸润（HR＝3.498, 95%CI 1.569～7.803, P＝0.002）是肿瘤特异性生存的独立危险因素。 结论膀胱复发灶肿瘤肌层浸润和高级别常发生于原发UTUC肌层浸润的患者，女性与男性相比容易发生多次膀胱复发。原发UTUC肌层浸润是UTUC膀胱复发患者肿瘤特异性生存的独立危险因素。

ObjectiveTo evaluate the risk factors and prognosis of high risk bladder recurrence developing after radical nephroureterectomy（RNU） for upper tract urothelial carcinoma （UTUC）. MethodsThe data of 148 UTUC patients who developed bladder tumor after RNU between January 2000 and December 2013 was retrospectively studied. There were 69 males and 79 females, aged from 34 to 82 years old（average 68 years old）. 83 patients were accompanied with hydronephrosis. 80 patients were renal pelvic carcinoma. 32 patients had the history of smoking. 24 patients had the history of ureteroscope. 68 patients had the tumor larger than 3 cm. Logistic regression model was used to analyze the risk factors of muscle invasive and high grade bladder recurrence lesions. We compared the clinocopathologic characteristics between primary UTUC and bladder cancer recurrence by using Fisher’s exact test. Cancer specific survival was analyzed using the Kaplan-Meier method, with the log-rank test used to assess significance. A Cox proportional hazard model was used for multivariate analysis. ResultsOf the 148 patients, non-muscle invasive （Tis、Ta and T1） tumors of primary UTUC and bladder recurrence were 51（34.5%） and 119（80.4%）, respectively. High grade （G3） tumors of primary UTUC and bladder recurrence were 41（27.7%） and 53（35.8%）, respectively. During follow-up, 94 （63.5%） experienced bladder recurrence once and 54 （36.5%） experienced multiple bladder recurrence. The median follow-up time was 59.5 （rang 8-142） months, 48 （32.4%） patients died of UTUC. The grade of bladder cancer recurrence correlated with the grade （P=0.046）, muscle-invasion （P=0.002） and tumor architecture （P=0.034） of the primary UTUC; muscle-invasive bladder cancer recurrence associated with that of the primary UTUC （P=0.009）; bladder multiple recurrence related to gender （P=0.007）. On multivariate logistic regression analysis, the muscle-invasion of primary UTUC was an independent risk factor for muscle-invasive （HR=5.512, 95%CI 1.654-18.37, P=0.004） and high grade （HR=3.948, 95%CI 1.589-9.813, P=0.004） bladder recurrence tumor. The muscle invasion of primary UTUC （HR=3.498, 95%CI 1.569-7.803, P=0.002） was a prognostic factor for cancer specific survival on multivariate Cox regression analysis. ConclusionsMuscle-invasive UTUC tend to predict high risk bladder recurrence tumor, and the female could be more likely to appear multiple recurrence tumor. The muscle invasion of primary UTUC could be an independent prognostic factor for cancer specific survival.