肿瘤大小对806例行根治手术的上尿路尿路上皮癌患者预后的分析

Prognostic value of tumor size for 806 patients with upper tract urothelial carcinoma after nephroureterectomy

目的:探讨肿瘤大小对行根治手术的上尿路尿路上皮癌(UTUC)患者预后的影响,以提高UTUC的诊治水平。方法:回顾性分析1998年1月～2016年3月于我院就诊的806例行根治性手术的UTUC患者的临床及预后资料,研究肿瘤大小(>3 cm)与临床病理因素对其预后的影响。男529例,女277例;年龄25～89岁,中位年龄67岁;390例伴有术前肾积水,119例合并糖尿病;肿瘤位于肾盂421例,位于输尿管317例,同时位于肾盂及输尿管68例。采用χ~2检验分析肿瘤大小与各临床病理因素的关系,运用Kaplan-Meier法及Log-rank检验进行生存分析,采用Cox比例风险模型进行单因素及多因素分析。结果:355例(44.0%)肿瘤直径>3 cm,451例(56.0%)肿瘤直径≤3 cm。806例的病理分级为低级别239例,高级别567例;病理分期为T_a及T_1期395例,T_2期133例,T_3期254例,T_4期24例;31例伴有鳞状或腺样分化;192例进行淋巴结清扫,其中51例病理证实淋巴结转移。随访2～206个月,中位随访时间41个月。随访期间共有202例因UTUC死亡,162例出现膀胱内肿瘤复发。肿瘤直径>3 cm的患者5年肿瘤特异性生存率(CSS)和膀胱内无复发生存率(IRFS)分别为67.3%和74.0%,均明显低于肿瘤≤3 cm患者的76.4%和78.0%(P<0.05)。肿瘤直径>3 cm的患者相较于肿瘤直径≤3 cm患者有着更高的肾盂+输尿管占位的比例(P<0.001)、病理分期(P=0.023)、淋巴结转移率(P=0.005)以及鳞状或腺样分化(P=0.019)。Cox多因素回归分析结果显示肿瘤直径>3 cm、年龄≥65岁、合并有糖尿病、肿瘤WHO高级别、肿瘤≥pT_2期、淋巴结转移是CSS的独立危险因素(P<0.05);而肿瘤直径>3 cm和肿瘤位置是IRFS的独立危险因素(P<0.05)。结论:UTUC恶性程度较高,肿瘤直径>3 cm是UTUC患者行根治术后CSS和IRFS的独立危险因素,对肿瘤大小行进一步的研究有助于术后对患者进行危险管理分层。

Objective: To determine the prognostic significance of tumor size on cancer-specific survival(CSS) and intravesical recurrence-free survival(IRFS) for patients with upper tract urothelial carcinoma(UTUC) after radical nephroureterecomy(RNU). Method: A retrospective review was performed on 806 patients who underwent RNU for UTUC in our hospital between January 1998 and March 2016. Among all the patients, 529 were male while 277 were female. The median age was 67(range, 25-89) years old. Among them, 390 patients were combined with hydronephrosis, 119 patients were combined with diabetes mellitus. Four hundred and twenty-one patients had tumor in the renal pelvic, 317 had tumor in the ureter and 68 had tumors in both sites. The χ2 test was used to detect the association between tumor size(≤3 cm versus >3 cm) and several clinicopathological features. Kaplan-Meier method with the log-rank test was used to assess CSS and IRFS. Multivariate analyses were conducted using Cox proportional-hazards regression model. Result: Median follow-up was 41(range, 2-206) months. Of all 806 patients included, 355 patients(44.0%) had a tumor >3 cm and 451 patients(56.0%) had a tumor ≤3 cm. Low pathological grade and high pathological grade were diagnosed in 239 and 567 patients, respectively. The distribution of pathological stage was pTa-1in 395 cases, pT2in 133, pT3in 254 and pT4in 24.Thirty-one patients were found squamous or glandular differentiation. One hundred and ninety-two patients received regional lymphadenectomy and positive lymph nodes were found in 51 patients. During follow-up, a total of 202 patients died of UTUC. Intravesical recurrence occurred in 162 patients. The five-year CSS and IRFS were 76.4% and 78.0% for patients with a tumor ≤3 cm while 67.3% and 74.0% with a tumor >3 cm(all P<0.05). Furthermore, patients with tumors >3 cm had a significantly higher rate of advanced tumor stage, tumor both in renal pelvic and ureter location, positive lymph node and squamous or glandular differentiation(all P<0.05). Multivariate analysis revealed that tumor size>3 cm was significantly associated with worse CSS and IRFS in patients with UTUC after RNU. Conclusion: UTUC had a poor prognosis and patients with larger tumor size(>3 cm) showed higher rate of aggressive biological characteristics and tended to have worse CSS and IRFS. Further studies on tumor size may be helpful for risk stratification.